Chloroform → N-(1-methylcyclobutyloxycarbonyl) aspartic acid dimethyl ester

HRID 1605190노트

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HRID 1605190 반응식
Cl.[CH3:2][O:3][C:4](=[O:12])[C@H:5]([CH2:7][C:8]([O:10][CH3:11])=[O:9])[NH2:6].C(Cl)(Cl)Cl.Cl[C:18]([O:20][C:21]1([CH3:25])[CH2:24][CH2:23][CH2:22]1)=[O:19]>C(N(CC)CC)C>[CH3:2][O:3][C:4](=[O:12])[C@H:5]([CH2:7][C:8]([O:10][CH3:11])=[O:9])[NH:6][C:18]([O:20][C:21]1([CH3:25])[CH2:24][CH2:23][CH2:22]1)=[O:19]

참가 물질

5

반응물 3

HCID 6212ChloroformHCID 2734892L-Aspartic acid, 1,4-dimethyl ester, hydrochloride (1:1)HCID 215491141-Methylcyclobutyl Chloroformate

생성물 1

HCID 54510473N-(1-methylcyclobutyloxycarbonyl) aspartic acid dimethyl ester

시약·촉매·용매 1

HCID 8471Triethylamine용매2회

실험 절차

A suspension of 0.05 moles of aspartic acid dimethyl ester hydrochloride in 50 ml. of chloroform is cooled to 0°C. and the pH adjusted to 8 by addition of triethylamine. 1-Methylcyclobutyl chloroformate 0.10 moles prepared according to the procedure of Example 1 is added portion-wise at 0°C. and the pH of the reaction is maintained at 8 by addition of triethylamine. Upon completion of the addition, the reaction is stirred overnight at 20°-25°C. The reaction solution is washed successively with 10 ml. portions of a saturated sodium bicarbonate solution, 50% saturated solution of sodium chloride, 0.2 N sulfuric acid saturated with sodium sulfate, 50% saturated solution of sodium chloride (twice), and the chloroform solution is dried over sodium acetate. Removal of the chloroform affords N-(1-methylcyclobutyloxycarbonyl)-aspartic acid dimethyl ester. Saponification is accomplished by dissolving the ester in 50 ml. of methanol, water 50 ml. is added, and the pH is adjusted to 12 by addition of 2 N sodium hydroxide. After stirring overnight at 25°C., the pH is adjusted to 7 with 2N sulfuric acid. The methanol is removed in vacuo and saturated sodium bicarbonate solution is added to the water solution. The aqueous bicarbonate solution is washed two times with ether and then the pH is adjusted to 3 by addition of concentrated hydrochloric acid. The acidified solution is extracted three times with ethyl acetate and the organic extracts combined, washed twice with sodium chloride solution and dried over sodium sulfate. The solvent is removed in vacuo to afford N-(1-methylcyclobutyloxycarbonyl) aspartic acid.

후처리

  1. additionis added portion-wise at 0°C.
  2. additionUpon completion of the addition
  3. washThe reaction solution is washed successively with 10 ml
  4. dry with materialportions of a saturated sodium bicarbonate solution, 50% saturated solution of sodium chloride, 0.2 N sulfuric acid saturated with sodium sulfate, 50% saturated solution of sodium chloride (twice), and the chloroform solution is dried over sodium acetate
  5. customRemoval of the chloroform

출처 및 근거

ORD 기록
ord-504bcdbbd64549f3bb64da4089ba249e
출처 데이터셋
uspto-grants-1976_04
특허 번호
US03948971

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