Methanol → N-(1-methylcyclobutyloxycarbonyl) aspartic acid

HRID 1605191Notes

Reaction equation

HRID 1605191 reaction equation
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

Participants

6

Reactant 4

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

Product 1

HCID 54120717N-(1-methylcyclobutyloxycarbonyl) aspartic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3c47a76e7823467789f34951422f67a9
Source dataset
uspto-grants-1976_04
Patent number
US03948971

Reaction notes

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