Hydrochloric Acid → N-(4-morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-L-alanine

HRID 326410Notes

Reaction equation

HRID 326410 reaction equation
Cl.C[O:3][C:4](=[O:34])[C@H:5]([CH2:27][C:28]1[N:29]=[C:30]([NH2:33])[S:31][CH:32]=1)[NH:6][C:7](=[O:26])[C@H:8]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[NH:9][S:10]([N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)(=[O:12])=[O:11].O1CCCC1.[OH-].[Na+].Cl>O>[N:13]1([S:10]([NH:9][C@H:8]([C:7]([NH:6][C@H:5]([C:4]([OH:34])=[O:3])[CH2:27][C:28]2[N:29]=[C:30]([NH2:33])[S:31][CH:32]=2)=[O:26])[CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)(=[O:11])=[O:12])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86745491N-(4-Morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-L-alanine methyl ester monohydrochloride

Product 1

HCID 11038203N-(4-morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-L-alanine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

N-(4-Morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-L-alanine methyl ester monohydrochloride, 2057.6 g, and 6 L of tetrahydrofuran are charged into a 50 L reactor and stirred to a thick slurry at 0° to 5° C. A solution of 456 g of sodium hydroxide in 11.4 L of water is added over 2 hours at 0° to 5° C. After stirring the reaction mixture for 30 minutes, a solution of 630.8 mL of concentrated hydrochloric acid in 7.6 L of water is added over 2 hours at 0° to 5° C. The product precipitates as a thick slurry, which is filtered and the cake washed with water (2×500 mL). The solid is dried under vacuum at 40° C. to give 1700 g of N-(4-morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-L-alanine as a white solid, 99.5% pure. A second crop of 108 g is obtained of 99.7% purity by HPLC; mp 149°-151° C.

Workup

  1. stirringAfter stirring the reaction mixture for 30 minutes
  2. customThe product precipitates as a thick slurry, which
  3. filtrationis filtered
  4. washthe cake washed with water (2×500 mL)
  5. customThe solid is dried under vacuum at 40° C.

Sources & evidence

ORD record
ord-2c9972ae9acf428787de2db1657dcca6
Source dataset
uspto-grants-1993_12
Patent number
US05268483

Reaction notes

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