A method for synthesizing tert-butyl 3-cyanopyridin-2-ylcarbamate

Abstract

The invention discloses a method for synthesizing tert-butyl 3-cyanopyridin-2-ylcarbamate, which is characterized by comprising the following steps: (1) reacting 2-chloronicotinonitrile and an ammonia solution to obtain 2-aminonicotinonitrile; (2) reacting 2-aminonicotinonitrile and Boc anhydride to obtain (3-cyanopyridin-2-yl)di-tert-butyl nitrile; and (3) reacting (3-cyanopyridin-2-yl)di-tert-butyl nitrile with a base to remove a molecule of Boc to obtain (3-cyanopyridin-2-yl)di-tert-butyl nitrile. The method has the advantages of simple process line, mild reaction conditions, high yield, low production cost and suitability for large-scale production.

Description

Technical Field

[0001] The present invention relates to the fields of medicine and pesticide intermediates, and in particular to a method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate. Background Art

[0002] Tert-butyl (3-cyanopyridin-2-yl)carbamate is an important pharmaceutical and pesticide intermediate. It can be used to synthesize pyridine methylamine compounds, a class of pyridine derivatives with insecticidal activity. They possess broad insecticide spectrum, high efficacy, low toxicity, good systemic plant transmissibility, and long-lasting effects, playing an important role in the development of new, highly effective pesticides. Furthermore, it can be used to synthesize 3-aminoazaindole compounds. Azaindole derivatives are frequently found in natural products and possess potent biological activity. Among them, 3-aminoindole, as a derivative of the indole skeleton, exhibits a wide range of biological activities, including antitumor, antimitotic, antimalarial, anti-influenza, and antimalarial activities. Furthermore, 3-aminoazaindole compounds have been identified as potential CXC chemokine receptor type 4 (CXCR4) receptor antagonists and inhibitors of heat shock protein 90 (Hsp90).

[0003] The synthesis of tert-butyl (3-cyanopyridin-2-yl)carbamate is rarely reported in the literature, with the only document reported being Tetrahedron, 2003, vol. 59, #31, pp. 5831-5836. This method uses 2-(tert-butyloxycarbonylamino)pyridine and phenyl cyanate as raw materials, which react with butyl lithium at ultra-low temperatures to obtain the target product in a 31% yield. This method suffers from high raw material costs and low yields, resulting in poor socioeconomic benefits. Furthermore, butyl lithium requires relatively low temperatures, and the reagents are expensive and highly flammable, making the operation complex and unsafe, resulting in high industrial costs. Therefore, this process is unsuitable for large-scale production. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate with a simple process line, mild reaction conditions, high yield, low production cost and suitability for large-scale production.

[0005] The technical solution adopted by the present invention to solve the above technical problems is: a method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate, comprising the following steps:

[0006] (1) reacting 2-chloronicotinonitrile with an ammonia solution to obtain 2-aminonicotinonitrile;

[0007] (2) reacting 2-aminonicotinonitrile with Boc anhydride to obtain di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate;

[0008] (3) Di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate is reacted with a base to remove one molecule of Boc to obtain tert-butyl (3-cyanopyridin-2-yl)carbamate.

[0009] The specific process of step (1) is as follows: after adding 2-chloronicotinonitrile to the ammonia solution, the temperature is slowly raised to T1 with stirring, 20°C≤T1≤200°C, and the reaction is maintained at T1 overnight. The next day, after the reaction is complete by TLC detection, the temperature is lowered to room temperature, and the reaction mixture is evaporated under reduced pressure. The residue is poured into ice water and stirred for 1 hour. The temperature is controlled not to exceed 5°C to form a precipitate, which is filtered and the filter cake is dried to obtain a light yellow solid 2-aminonicotinonitrile.

[0010] Furthermore, the ammonia solution is ethanol ammonia solution, methanol ammonia solution and ammonia water.

[0011] The specific process of step (2) is as follows: 2-amino-3-cyanopyridine is dissolved in a solvent, and then a catalyst N,N-dimethyl-4-aminopyridine is added. After the addition is completed, the mixture is cooled to 5°C in an ice-water bath, and di-tert-butyl dicarbonate is added dropwise. The reaction is exothermic and the temperature is controlled not to be higher than 15°C. After the addition is completed, the temperature is controlled to react at T2, 10°C ≤ T2 ≤ 100°C. After TLC detection shows that the reaction is complete, the reaction mixture is evaporated under reduced pressure, dichloromethane is added to the residue, and after stirring to dissolve clearly, the mixture is washed twice with saturated brine, dried over anhydrous sodium sulfate, and desolvated under reduced pressure to obtain a yellow solid (3-cyanopyridin-2-yl) di-tert-butyl nitrite.

[0012] Furthermore, the solvent is one of acetonitrile, 1,4-dioxane, tetrahydrofuran, DMF, DMSO, or any combination thereof.

[0013] Furthermore, the molar ratio of the 2-amino-3-cyanopyridine to di-tert-butyl dicarbonate is 1:(1-5).

[0014] The specific process of step (3) is as follows: dissolving di-tert-butyl (3-cyanopyridin-2-yl) nitrodicarboxylate in a solvent, then adding basic carbonate, stirring at room temperature for 1 hour, then controlling the temperature to react at T3, 10°C ≤ T3 ≤ 100°C, after TLC detection, evaporating the reaction mixture to dryness under reduced pressure, adding the residue to water, stirring to dissolve clearly, extracting with dichloromethane three times, combining the organic phases, washing the organic phases twice with saturated brine, drying over anhydrous sodium sulfate, and desolvating under reduced pressure to obtain tert-butyl (3-cyanopyridin-2-yl) carbamate.

[0015] Furthermore, the solvent is one of ethanol, methanol, isopropanol, 1,4-dioxane, tetrahydrofuran, DMF and DMSO, or any combination thereof; and the basic carbonate is one of potassium carbonate, sodium carbonate, cesium carbonate and ammonium carbonate.

[0016] Furthermore, the molar ratio of the di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate to the basic carbonate is 1:(1-7).

[0017] Compared with the prior art, the present invention has the advantages of: disclosing a method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate; the method comprises three steps: using 2-chloronicotinonitrile as a raw material, first reacting with an ammonia solution to obtain 2-aminonicotinonitrile; then reacting with Boc anhydride to obtain di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate; and finally removing one molecule of Boc to obtain tert-butyl (3-cyanopyridin-2-yl)carbamate; and the method comprising three steps. The method has a wide source of raw materials, is low in price, has mild reaction conditions, is simple to operate, has a high yield, is suitable for large-scale industrial production, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The present invention provides a nuclear magnetic resonance spectrum of tert-butyl (3-cyanopyridin-2-yl)carbamate synthesized by the present invention. DETAILED DESCRIPTION

[0019] The present invention will be described in further detail below with reference to the accompanying drawings and embodiments. Specific embodiments

[0021] A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate, characterized by comprising the following steps

[0022] (1) reacting 2-chloronicotinonitrile with an ammonia solution to obtain 2-aminonicotinonitrile;

[0023] (2) reacting 2-aminonicotinonitrile with Boc anhydride to obtain di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate;

[0024] (3) Di-tert-butyl (3-cyanopyridin-2-yl) nitrodicarboxylate is reacted with a base to remove one molecule of Boc to obtain tert-butyl (3-cyanopyridin-2-yl) carbamate. The synthetic route is as follows:

[0025]

[0026] The specific process of the above step (1) is as follows: after adding 2-chloronicotinonitrile to the ammonia solution, the temperature is slowly raised to T1 with stirring, 20°C≤T1≤200°C, and the reaction is maintained at T1 overnight. The next day, after the reaction is complete, TLC is detected, the temperature is lowered to room temperature, and the reaction mixture is evaporated under reduced pressure. The residue is poured into ice water and stirred for 1 hour, with the temperature controlled not to exceed 5°C to form a precipitate, which is filtered and the filter cake is dried to obtain a light yellow solid 2-aminonicotinonitrile. The ammonia solution is ethanol ammonia solution, methanol ammonia solution, and ammonia water.

[0027] The specific process of the above step (2) is as follows: 2-amino-3-cyanopyridine is dissolved in a solvent, and then a catalyst N,N-dimethyl-4-aminopyridine is added. After the addition is completed, the temperature is cooled to 5°C in an ice-water bath, and di-tert-butyl dicarbonate is added dropwise. The reaction is exothermic and the temperature is controlled not to exceed 15°C. After the addition is completed, the temperature is controlled to react at T2, 10°C ≤ T2 ≤ 100°C. After TLC detection shows that the reaction is complete, the reaction mixture is evaporated under reduced pressure, and dichloromethane is added to the residue. After stirring and dissolving, the mixture is washed twice with saturated brine, dried over anhydrous sodium sulfate, and desolvated under reduced pressure to obtain a yellow solid (3-cyanopyridin-2-yl) di-tert-butyl nitrite. The solvent is one of acetonitrile, 1,4-dioxane, tetrahydrofuran, DMF, and DMSO, or any combination thereof; the molar ratio of 2-amino-3-cyanopyridine to di-tert-butyl dicarbonate is 1:(1-5).

[0028] The specific process of the above step (3) is as follows: dissolve di-tert-butyl (3-cyanopyridin-2-yl) nitrodicarboxylate in a solvent, then add basic carbonate, stir at room temperature for 1 hour, and then control the temperature at T3, 10°C

[0029] The reaction is carried out at ≤T3≤100°C. After TLC determination of the reaction is complete, the reaction mixture is evaporated to dryness under reduced pressure. The residue is added to water, stirred to dissolve, and then extracted three times with dichloromethane. The organic phases are combined, washed twice with saturated brine, dried over anhydrous sodium sulfate, and desolventized under reduced pressure to obtain tert-butyl (3-cyanopyridin-2-yl)carbamate. The solvent is one or any combination of ethanol, methanol, isopropanol, 1,4-dioxane, tetrahydrofuran, DMF, and DMSO; the basic carbonate is one of potassium carbonate, sodium carbonate, cesium carbonate, and ammonium carbonate. The molar ratio of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate to the basic carbonate is 1:(1-7).

[0030] Example 1

[0031] 1. Synthesis of 2-aminonicotinonitrile

[0032] To a 5-L autoclave were added 3 L of saturated ethanolamine solution and 120 g (0.87 mol) of 2-chloronicotinonitrile. After the addition was complete, the temperature was slowly raised to 130° C. with stirring and maintained at this temperature overnight. The next day, TLC detected that the reaction was complete, with EA:PE = 1:2 (Rf = 0.3). The temperature was then lowered to room temperature, and the reaction mixture was evaporated to dryness under reduced pressure. The residue was poured into 1 kg of ice water and stirred for 1 hour, controlling the temperature not to exceed 5° C., to form a precipitate. The precipitate was filtered and the filter cake was dried to obtain 90 g of 2-aminonicotinonitrile as a pale yellow solid with an MP of 133-135 and a yield of 87%.

[0033] 2. Synthesis of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate

[0034] To a 1L reaction flask, add 300mL of tetrahydrofuran, and add 24g (0.20mol) of 2-amino-3-cyanopyridine and 2g of 4-dimethylaminopyridine with stirring at room temperature. After the addition, cool to 5°C in an ice-water bath, and begin to add 99g (0.45mol) of di-tert-butyl dicarbonate (dissolved in 200ml of tetrahydrofuran) dropwise. The reaction is exothermic, and the temperature is controlled not to exceed 15°C. After the addition is complete, stir at room temperature for 1 hour, then raise the temperature to 35°C and react overnight. The next day, TLC detected that the reaction was complete, EA:PE=1:2 (Rf=0.6). The temperature was cooled to room temperature, and then the reaction mixture was evaporated under reduced pressure. The residue was added with 300 mL of dichloromethane, stirred to dissolve clearly, and then washed twice with saturated brine (100 mL×2), dried over anhydrous sodium sulfate, and desolventized under reduced pressure. The residue was added with 200 mL of petroleum ether, cooled to 5°C in an ice-water bath, stirred for 0.5 hour, a precipitate was formed, filtered, and the filter cake was dried to obtain 61 g of a yellow solid with a yield of 95%.

[0035] 3. Synthesis of tert-butyl (3-cyanopyridin-2-yl)carbamate

[0036] 900 ml of methanol was added to a 1 L reaction flask. 32 g (0.10 mol) of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate and 50 g (0.36 mol) of potassium carbonate were added with stirring. After the addition was complete, the reaction was stirred at room temperature overnight. The next day, TLC confirmed the reaction was complete. The reaction mixture was then evaporated to dryness under reduced pressure. The residue was added to 200 ml of water and stirred to dissolve. The mixture was then extracted with dichloromethane (200 mL x 3). The organic phases were combined and washed twice with saturated brine (100 mL x 2), dried over anhydrous sodium sulfate, and desolvated under reduced pressure. 100 mL of petroleum ether was added to the residue, and the mixture was cooled to 5°C in an ice-water bath. Stirring occurred for 0.5 hours to form a precipitate. The precipitate was filtered and the filter cake was dried to obtain 20.5 g of a white solid with a yield of 93%. The NMR spectrum of tert-butyl (3-cyanopyridin-2-yl)carbamate is shown below. Figure 1 As shown, 1H NMR (400 MHz, DMSO-d6): δ 1.58 (s, 9H), 7.15 (dd, J = 7.6, 4.8 Hz, 1H), 7.90 (br.s, 1H) 7.97 (d, J = 7.6 Hz, 1H), 8.63 (d, J = 4.8 Hz, 1H).

[0037] Example 2

[0038] 1. Synthesis of 2-aminonicotinonitrile

[0039] To a 5-L autoclave were added 3 L of saturated ethanolamine solution and 120 g (0.87 mol) of 2-chloronicotinonitrile. After the addition was complete, the temperature was slowly raised to 170°C with stirring and maintained overnight. The next day, TLC detected that the reaction was complete, with EA:PE = 1:2 (Rf = 0.3). The temperature was then lowered to room temperature, and the reaction mixture was evaporated under reduced pressure. The residue was poured into 1 kg of ice water and stirred for 1 hour, controlling the temperature not to exceed 5°C. A precipitate formed, which was filtered and the filter cake was dried to obtain 81 g of 2-aminonicotinonitrile as a pale yellow solid with MP: 133-135, in a yield of 78%.

[0040] 2. Synthesis of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate

[0041] To a 1L reaction flask, add 300mL of tetrahydrofuran, and add 24g (0.20mol) of 2-amino-3-cyanopyridine and 2g of 4-dimethylaminopyridine with stirring at room temperature. After the addition, cool to 5°C in an ice-water bath, and begin to add 99g (0.45mol) of di-tert-butyl dicarbonate (dissolved in 200ml of tetrahydrofuran) dropwise. The reaction is exothermic, and the temperature is controlled not to exceed 15°C. After the addition is complete, stir the reaction at room temperature overnight. The next day, TLC detected that the reaction was complete, EA:PE=1:2 (Rf=0.6). The temperature was cooled to room temperature, and then the reaction mixture was evaporated to dryness under reduced pressure. The residue was added with 300 mL of dichloromethane, stirred to dissolve clearly, and then washed twice with saturated brine (100 mL×2), dried over anhydrous sodium sulfate, and desolventized under reduced pressure. The residue was added with 200 mL of petroleum ether, cooled to 5°C in an ice-water bath, stirred for 0.5 hour, a precipitate was formed, filtered, and the filter cake was dried to obtain 58 g of a yellow solid with a yield of 90%.

[0042] 3. Synthesis of tert-butyl (3-cyanopyridin-2-yl)carbamate

[0043] 900 ml of methanol was added to a 1 L reaction flask, and 32 g (0.10 mol) of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate and 50 g (0.36 mol) of potassium carbonate were added under stirring. After the addition was completed, the mixture was stirred at room temperature for 1 hour, then the temperature was raised to 40 ° C for 2 hours, the reaction was complete by TLC detection, and the temperature was lowered to room temperature. Then, the reaction mixture was evaporated under reduced pressure, 200 ml of water was added to the residue and stirred to dissolve it, and then it was extracted with dichloromethane (200 mL * 3), the organic phases were combined, and the organic phases were washed twice with saturated brine (100 mL × 2), dried over anhydrous sodium sulfate, and desolvated under reduced pressure. 100 mL of petroleum ether was added to the residue, the temperature was lowered to 5 ° C in an ice-water bath, and stirred for 0.5 hours to form a precipitate. The precipitate was filtered and the filter cake was dried to obtain 19 g of a white solid with a yield of 87%.

[0044] Example 3

[0045] 1. Synthesis of 2-aminonicotinonitrile

[0046] To a 5-L autoclave were added 3 L of 25 wt% concentrated aqueous ammonia and 120 g (0.87 mol) of 2-chloronicotinonitrile. After the addition was complete, the temperature was slowly raised to 170° C. with stirring and maintained overnight. The next day, TLC detected that the reaction was complete, with EA:PE = 1:2 (Rf = 0.3). The temperature was then lowered to room temperature, and the reaction mixture was evaporated under reduced pressure. The residue was poured into 1 kg of ice water and stirred for 1 hour, controlling the temperature not to exceed 5° C., to form a precipitate. The precipitate was filtered and the filter cake was dried to obtain 77 g of 2-aminonicotinonitrile as a pale yellow solid with an MP of 133-135 (yield of 75%).

[0047] 2. Synthesis of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate

[0048] To a 1L reaction flask, add 300mL of tetrahydrofuran, and add 24g (0.20mol) of 2-amino-3-cyanopyridine and 2g of 4-dimethylaminopyridine with stirring at room temperature. After the addition, cool to 5°C in an ice-water bath, and begin to add 99g (0.45mol) of di-tert-butyl dicarbonate (dissolved in 200ml of tetrahydrofuran) dropwise. The reaction is exothermic, and the temperature is controlled not to exceed 15°C. After the addition is complete, stir at room temperature for 1 hour, then raise the temperature to 65°C and react overnight. The next day, TLC detected that the reaction was complete, EA:PE=1:2 (Rf=0.6). The temperature was cooled to room temperature, and then the reaction mixture was evaporated to dryness under reduced pressure. The residue was added with 300 mL of dichloromethane, stirred to dissolve, and then washed twice with saturated brine (100 mL×2), dried over anhydrous sodium sulfate, and desolventized under reduced pressure. The residue was added with 200 mL of petroleum ether, cooled to 5°C in an ice-water bath, stirred for 0.5 hour, and a precipitate was formed. The precipitate was filtered and the filter cake was dried to obtain 56 g of a yellow solid with a yield of 87%.

[0049] 3. Synthesis of tert-butyl (3-cyanopyridin-2-yl)carbamate

[0050] 900 ml of methanol was added to a 1 L reaction flask, and 32 g (0.10 mol) of di-tert-butyl (3-cyanopyridin-2-yl)nitrodicarboxylate and 50 g (0.36 mol) of potassium carbonate were added under stirring. After the addition was completed, the mixture was stirred at room temperature for 1 hour, then heated to 65 ° C for 2 hours, and the reaction was complete by TLC detection. The mixture was cooled to room temperature and then evaporated to dryness under reduced pressure. The residue was added with 200 ml of water and stirred to dissolve clearly, and then extracted with dichloromethane (200 mL * 3). The organic phases were combined and washed twice with saturated brine (100 mL × 2), dried over anhydrous sodium sulfate, and desolvated under reduced pressure. 100 mL of petroleum ether was added to the residue, cooled to 5 ° C in an ice-water bath, stirred for 0.5 hours, a precipitate was formed, filtered, and the filter cake was dried to obtain 18 g of a white solid with a yield of 81%.

[0051] The above description is not intended to limit the present invention, and the present invention is not limited to the above examples. Any changes, modifications, additions or substitutions made by persons of ordinary skill in the art within the spirit and scope of the present invention shall also fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate, characterized in that The following steps are included (1) reacting 2-chloronicotinonitrile with an ammonia solution to obtain 2-aminonicotinonitrile, wherein the specific process is as follows: after the addition of 2-chloronicotinonitrile to the ammonia solution is completed, the temperature is slowly raised to T1 with stirring, 20°C≤T1≤200°C, and the temperature is maintained at T1 for overnight reaction. The next day, after the reaction is complete by TLC detection, the temperature is lowered to room temperature, and the reaction mixture is evaporated under reduced pressure. The residue is poured into ice water and stirred for 1 hour. The temperature is controlled not to be higher than 5°C to form a precipitate, which is filtered and the filter cake is dried to obtain a light yellow solid 2-aminonicotinonitrile; (2) reacting 2-aminonicotinonitrile and Boc anhydride to obtain (3-cyanopyridin-2-yl)di-tert-butyl nitrile, wherein the specific process is as follows: dissolving 2-amino-3-cyanopyridine in a solvent, and then adding a catalyst N,N-dimethyl-4-aminopyridine. After the addition is completed, cooling to 5°C in an ice-water bath, and then dropping di-tert-butyl dicarbonate. The reaction is exothermic, and the temperature is controlled not to be higher than 15°C. After the dropwise addition is completed, the temperature is controlled to be T2, 10°C≤T2≤100°C. After the reaction is complete as detected by TLC, the reaction mixture is evaporated to dryness under reduced pressure, and dichloromethane is added to the residue. After stirring to dissolve, the mixture is washed twice with saturated brine, dried over anhydrous sodium sulfate, and desolventized under reduced pressure to obtain a yellow solid (3-cyanopyridin-2-yl)di-tert-butyl nitrile; (3) Releasing di-tert-butyl (3-cyanopyridin-2-yl) nitrobenzene with a base to remove one molecule of Boc to obtain tert-butyl (3-cyanopyridin-2-yl) carbamate. The specific process is as follows: dissolving di-tert-butyl (3-cyanopyridin-2-yl) nitrobenzene in a solvent, then adding a basic carbonate, stirring at room temperature for 1 hour, then controlling the temperature to react at T3, 10°C ≤ T3 ≤ 100°C, after TLC detection, evaporating the reaction mixture to dryness under reduced pressure, adding the residue to water, stirring to dissolve, extracting with dichloromethane 3 times, combining the organic phases, washing the organic phases twice with saturated brine, drying over anhydrous sodium sulfate, and desolventizing under reduced pressure to obtain tert-butyl (3-cyanopyridin-2-yl) carbamate.

2. A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate according to claim 1, characterized in that: The ammonia solution is ethanol ammonia solution, methanol ammonia solution and aqueous ammonia.

3. A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate according to claim 1, characterized in that: The solvent of step (2) is one of acetonitrile, 1,4-dioxane, tetrahydrofuran, DMF, DMSO or any combination thereof.

4. A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate according to claim 1, characterized in that: The molar ratio of the 2-amino-3-cyanopyridine to di-tert-butyl dicarbonate is 1:(1-5).

5. A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate according to claim 1, characterized in that: The solvent of step (3) is one of ethanol, methanol, isopropanol, 1,4-dioxane, tetrahydrofuran, DMF and DMSO or any combination thereof; the basic carbonate is one of potassium carbonate, sodium carbonate, cesium carbonate and ammonium carbonate.

6. A method for synthesizing tert-butyl (3-cyanopyridin-2-yl)carbamate according to claim 1, characterized in that: The molar ratio of the (3-cyanopyridine-2-yl) nitrous acid di-tert-butyl ester to the basic carbonate is 1:(1-7).

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