Potassium Hydroxide → 2-[3-Cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid

HRID 1935226Notes

Reaction equation

HRID 1935226 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:33])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:22][CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)=[O:5])C.[OH-].[K+]>C(O)C.O>[CH:15]1([CH2:14][CH:13]([C:20]2[CH:21]=[CH:22][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:24][CH:25]=2)[C:12]([NH:11][C:8]2[S:9][CH:10]=[C:6]([C:4]([OH:5])=[O:3])[N:7]=2)=[O:33])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 865841372-[3-Cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester

Product 1

HCID 224679272-[3-Cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acidYield 80%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-[3-cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester (prepared in Example 13, 300 mg, 0.65 mmol) in ethanol (20 mL) at 25° C. was treated with a solution of potassium hydroxide (109 mg, 1.94 mmol) in water (6 mL). This light yellow solution was stirred at 25° C. for 2 h and then concentrated in vacuo to remove ethanol. The resulting aqueous solution was acidified to pH=2 with a 1N aqueous hydrochloric acid solution and then extracted with methylene chloride (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 20/80 hexanes/ethyl acetate plus 1% acetic acid) afforded 2-[3-cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid (226 mg, 80%) as a white solid: mp >200° C.; FAB-HRMS m/e calcd for C24H24N2O4S (M+H)+ 437.1535, found 437.1534.

Workup

  1. concentrationconcentrated in vacuo
  2. customto remove ethanol
  3. extractionextracted with methylene chloride (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e933cad4dd8347fe98e2bbe04f43a2a1
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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