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

HRID 1605190ノート

反応式

HRID 1605190 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-504bcdbbd64549f3bb64da4089ba249e
出典データセット
uspto-grants-1976_04
特許番号
US03948971

反応ノート

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