Method for synthesizing optically active derivative of 5 - aryl - (S) - N - boc - alpha amino pentanoic acid
A tert-butoxycarbonyl and optically active technology, which is applied in the field of synthesis of 5-aryl--N-tert-butoxycarbonyl-α-aminovaleric acid derivatives, can solve the problem of reducing synthesis cost, impossibility of industrial production, and synthesis time Long and other problems, to achieve the effect of shortening the synthesis time and choosing a reasonable reaction process
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Embodiment 1
[0026] 【5-Phenyl-5-keto-(S)-N-tert-butoxycarbonyl-α-aminovalerate ethyl ester (3a)】Synthesis:
[0027]
[0028] First prepare the Grignard reagent (2a) of bromobenzene, equipped with a dropping funnel and a three-necked flask with an internal thermometer, put Mg (0.77g, 32mmol) and dried tetrahydrofuran (30mL), and replace it with nitrogen, A solution of bromobenzene (5.1 g, 32 mmol) in dry tetrahydrofuran (10 mL) was prepared in a dropping funnel. Start to drop 2mL of this solution to initiate the reaction, then slowly drop the rest, maintaining the internal temperature at 60-70°C.
[0029] N-tert-butoxycarbonyl-L-pyroglutamic acid ethyl ester (1) (7g, 27mmol) in dry tetrahydrofuran (100mL) was cooled to between minus 50°C and minus 40°C with dry ice, acetone and water system, drop Add the above-mentioned Grignard reagent 2a (40mL, 32mmol), after the addition is completed, the reaction solution is stirred at this temperature for 60 minutes, rises to minus 10°C, and is the...
Embodiment 2
[0034] Synthesis of [5-p-methoxyphenyl-5-one-(S)-N-tert-butoxycarbonyl-α-aminovaleric acid ethyl ester (3b)]:
[0035]
[0036] N-tert-butoxycarbonyl-L-pyroglutamic acid ethyl ester (1) (4.6g, 18mmol) in dry tetrahydrofuran (100mL) was cooled to between minus 50°C and minus 40°C with dry ice, acetone and water, Grignard reagent (2b) (40mL, 20mmol) of p-methoxybromobenzene was added dropwise, and the dropwise addition was completed. The reaction solution was stirred at this temperature for 60 minutes, raised to minus 10°C, and then washed with 10% saturated NH 4 Cl aqueous solution was quenched, the organic layer was separated, the aqueous layer was extracted three times with 50 mL of diethyl ether, the combined organic layer was washed with water and saturated brine, and then washed with anhydrous Na 2 SO 4 Drying, filtration, rotary evaporation, column chromatography (petroleum ether / ethyl acetate=20:1) to obtain the target product 5-p-methoxyphenyl-5-one-(S)-N-tert-butoxyc...
Embodiment 3
[0041] Synthesis of [5-p-methoxyphenyl-5-one-(S)-N-tert-butoxycarbonyl-α-aminovaleric acid ethyl ester (3b)]:
[0042]
[0043] N-tert-butoxycarbonyl-L-pyroglutamic acid ethyl ester (1) (4.6g, 18mmol) in dry tetrahydrofuran (100mL) was cooled to between minus 50°C and minus 40°C with dry ice, acetone and water, Grignard reagent (2b) (40mL, 20mmol) was added dropwise to p-methoxybromobenzene, and the dropwise addition was completed. The reaction solution was stirred at this temperature for 60 minutes, raised to minus 10°C, and then washed with 10% saturated NH 4 Cl aqueous solution was quenched, the organic layer was separated, the aqueous layer was extracted three times with 50 mL of diethyl ether, the combined organic layer was washed with water and saturated brine, and then washed with anhydrous Na 2 SO 4 Drying, filtration, rotary evaporation, column chromatography (petroleum ether / ethyl acetate=20:1) to obtain the target product 5-p-methoxyphenyl-5-one-(S)-N-tert-butox...
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