Methanol → N-(1-methylcyclobutyloxycarbonyl) aspartic acid

HRID 1605191ノート

反応式

HRID 1605191 の反応式
C[O:2][C:3](=[O:19])[C@H:4]([CH2:14][C:15]([O:17]C)=[O:16])[NH:5][C:6]([O:8][C:9]1([CH3:13])[CH2:12][CH2:11][CH2:10]1)=[O:7].CO.[OH-].[Na+].S(=O)(=O)(O)O>O>[CH3:13][C:9]1([O:8][C:6]([NH:5][C@H:4]([C:3]([OH:19])=[O:2])[CH2:14][C:15]([OH:17])=[O:16])=[O:7])[CH2:12][CH2:11][CH2:10]1

参加物

6

反応物 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 54510473N-(1-methylcyclobutyloxycarbonyl) aspartic acid dimethyl ester

生成物 1

HCID 54120717N-(1-methylcyclobutyloxycarbonyl) aspartic acid

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
25 °C

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
  2. customThe methanol is removed in vacuo and saturated sodium bicarbonate solution
  3. additionis added to the water solution
  4. washThe aqueous bicarbonate solution is washed two times with ether
  5. additionthe pH is adjusted to 3 by addition of concentrated hydrochloric acid
  6. extractionThe acidified solution is extracted three times with ethyl acetate
  7. washwashed twice with sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. customThe solvent is removed in vacuo

出典と根拠

ORDレコード
ord-3c47a76e7823467789f34951422f67a9
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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