Acetic Acid → HCID 21715924, compound

HRID 1250987Notes

Reaction equation

HRID 1250987 reaction equation
C([S:4][CH:5]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:6]([NH:8][CH:9]1[C:15](=[O:16])[N:14]([CH2:17][C:18]([OH:20])=[O:19])[C:13]([CH3:22])([CH3:21])[CH2:12][CH2:11][CH2:10]1)=[O:7])(=O)C.SCC(C(CS)O)O.[OH-].[Na+].C(O)(=O)C>>[SH:4][CH:5]([CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:6]([NH:8][CH:9]1[C:15](=[O:16])[N:14]([CH2:17][C:18]([OH:20])=[O:19])[C:13]([CH3:21])([CH3:22])[CH2:12][CH2:11][CH2:10]1)=[O:7]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium Hydroxide2×HCID 190011,4-Dimercapto-2,3-butanediolHCID 5251328{6-[2-(Acetylsulfanyl)-3-phenylpropanamido]-2,2-dimethyl-7-oxoazepan-1-yl}acetic acid

Product 1

HCID 21715924HCID 21715924, compoundYield 93.9%

Conditions

Temperature
1 °C

Procedure

A three necked flask was charged with [S-(R*,R*) ]-6-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]hexahydro-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid (10 g, 23.78 mmoles) and D,L-dithiothreitol (390 mg, 2.5 mmoles). The flask was flushed with nitrogen. Deoxygenated water (20 ml) was added to the flask and the mixture was cooled to 1° C. Cold (1° C.) deoxygenated sodium hydroxide solution (1.22 N, total 70 ml, 84 mmoles) was added slowly while maintaining the temperature of the reaction mixture between 1° C. and 4° C. After addition of the initial 10 v/v% of the sodium hydroxide solution, the remainder of the solution was added, maintaining the reaction temperature between −2° to 30° C. After stirring the reaction mixture at −2° to 6° C. for 30 minutes, the reaction mixture was allowed to warm to room temperature. The reaction mixture was polish filtered into a crystallization flask and heated to 45° C. Deoxygenated acetic acid solution (1.06 N, 90 ml, 95 mmoles) was added while maintaining the reaction temperature between 41° and 46° C. The crystal slurry was stirred at 41° to 46° C. for 20 minutes and then allowed to cool to room temperature. After stirring at room temperature for 30 minutes, the product was filtered and washed with water (100 ml) and dried in a vacuum oven at 51° C./4.1 inch Hg to afford 8.45 g of title product having laboratory HPLC of 99.75 area percent.

Workup

  1. customThe flask was flushed with nitrogen
  2. additionDeoxygenated water (20 ml) was added to the flask
  3. additionwas added slowly
  4. temperaturewhile maintaining the temperature of the reaction mixture between 1° C. and 4° C
  5. additionthe remainder of the solution was added
  6. temperaturemaintaining the reaction temperature between −2° to 30° C
  7. temperatureto warm to room temperature
  8. filtrationfiltered into a crystallization flask
  9. temperatureheated to 45° C
  10. temperaturewhile maintaining the reaction temperature between 41° and 46° C
  11. stirringThe crystal slurry was stirred at 41° to 46° C. for 20 minutes
  12. temperatureto cool to room temperature
  13. stirringAfter stirring at room temperature for 30 minutes
  14. filtrationthe product was filtered
  15. washwashed with water (100 ml)
  16. customdried in a vacuum oven at 51° C./4.1 inch Hg

Sources & evidence

ORD record
ord-6ccd2c2c96244e0c906d359719da29c8
Source dataset
uspto-grants-2002_01
Patent number
US06340752B1

Reaction notes

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