Preparation method of Boc-1-(benzyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate

Abstract

The invention relates to a synthesis method of tert-butoxycarbonyl-1-(benzyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate, and mainly solve the technical problem that no synthesis method suitablefor industrialization exists at present. The method is divided into three steps: the first step, a compound 1 and benzylamine are reacted to obtain a compound 2 in the solvent toluene under the action of potassium carbonate; the second step, the compound 2 and allyl magnesium bromide are reacted to obtain a compound 3 in toluene; and the third step, the compound 3 and iodine are reacted to obtaina final compound 4 in the solvent acetonitrile under the action of sodium bicarbonate. The reaction formula is as shown in the specification.

Description

technical field

[0001] The present invention relates to the preparation method of Boc-1-(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate, namely the compound tert-butoxycarbonyl-1 Synthetic method of -(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate. Background technique

[0002] The compound tert-butoxycarbonyl-1-(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate (MFCD28390464) and related derivatives in the pharmaceutical It is widely used in chemistry and organic synthesis. At present, there are few reports on the synthesis methods of tert-butoxycarbonyl-1-(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate. Therefore, it is necessary to develop a synthetic method that is easy to obtain raw materials, easy to operate, easy to control the reaction, suitable for overall yield, and suitable for industrial production. Contents of the invention

[0003] The purpose of this invention is to develop a kind of tert-butoxy...

Examples

Embodiment 1

[0012] Compound 1 (4.06 kg, 20.38 mol, 1.00 eq ) was dissolved in toluene (35.00 L), then potassium carbonate (5.63 kg, 40.76 mol, 2.00 eq ) and benzylamine (3.28 kg, 30.57 mol, 3.34 L, 1.50 eq ). Then reacted at 60°C for 18 hours, and the nuclear magnetic resonance of the crude product showed that the reaction was complete. The reaction system was cooled to 25°C, filtered, and the filtrate was spin-dried to obtain crude compound 2.

[0013] Compound 2 (5.88 kg, 20.39 mol, 1.00 eq) was dissolved in toluene (40.00 L), then allylmagnesium bromide (1 M, 24.06 L, 1.5 eq) was added dropwise at 0°C, and reacted at 25°C for 18 hours . TLC (petroleum ether / ethyl acetate volume ratio = 3 / 1) showed that the reaction was complete. The reaction solution was quenched by adding saturated ammonium chloride (40 L). Then it was extracted with ethyl acetate (40L*4), the organic phase was washed with brine, dried and concentrated to obtain the crude product. The crude product was separate...

technical field

[0001] The present invention relates to the preparation method of Boc-1-(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate, namely the compound tert-butoxycarbonyl-1 Synthetic method of -(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate. Background technique

[0002] The compound tert-butoxycarbonyl-1-(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate (MFCD28390464) and related derivatives in the pharmaceutical It is widely used in chemistry and organic synthesis. At present, there are few reports on the synthesis methods of tert-butoxycarbonyl-1-(phenylmethyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate. Therefore, it is necessary to develop a synthetic method that is easy to obtain raw materials, easy to operate, easy to control the reaction, suitable for overall yield, and suitable for industrial production. Contents of the invention

[0003] The purpose of this invention is to develop a kind of tert-butoxy...

Examples

Embodiment 1

[0012] Compound 1 (4.06 kg, 20.38 mol, 1.00 eq ) was dissolved in toluene (35.00 L), then potassium carbonate (5.63 kg, 40.76 mol, 2.00 eq ) and benzylamine (3.28 kg, 30.57 mol, 3.34 L, 1.50 eq ). Then reacted at 60°C for 18 hours, and the nuclear magnetic resonance of the crude product showed that the reaction was complete. The reaction system was cooled to 25°C, filtered, and the filtrate was spin-dried to obtain crude compound 2.

[0013] Compound 2 (5.88 kg, 20.39 mol, 1.00 eq) was dissolved in toluene (40.00 L), then allylmagnesium bromide (1 M, 24.06 L, 1.5 eq) was added dropwise at 0°C, and reacted at 25°C for 18 hours . TLC (petroleum ether / ethyl acetate volume ratio = 3 / 1) showed that the reaction was complete. The reaction solution was quenched by adding saturated ammonium chloride (40 L). Then it was extracted with ethyl acetate (40L*4), the organic phase was washed with brine, dried and concentrated to obtain the crude product. The crude product was separate...

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