Hydrochloric Acid → cis(+/-)-2-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylic acid

HRID 43837Notes

Reaction equation

HRID 43837 reaction equation
[OH-].[Li+].[Cl:3][C:4]1[N:5]=[C:6]([C:11]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([C:20]3[S:21][C:22]([C:26]([O:28]CC)=[O:27])=[C:23]([CH3:25])[N:24]=3)[CH2:16][C@H:15]2[F:31])=[O:12])[NH:7][C:8]=1[CH2:9][CH3:10].Cl.O>CO.O1CCCC1>[Cl:3][C:4]1[N:5]=[C:6]([C:11]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([C:20]3[S:21][C:22]([C:26]([OH:28])=[O:27])=[C:23]([CH3:25])[N:24]=3)[CH2:16][C@H:15]2[F:31])=[O:12])[NH:7][C:8]=1[CH2:9][CH3:10]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 86648767Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylate

Product 1

HCID 86648768cis(+/-)-2-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylic acidYield 73.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A 2 N aqueous lithium hydroxide solution (1.18 mL, 2.37 mmol) was added to a mixed solution of ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylate obtained in Example (196c) (105 mg, 0.237 mmol) in methanol (3 mL) and tetrahydrofuran (3 mL) at room temperature, and the mixture was stirred at 70° C. for two hours. The reaction solution was concentrated under reduced pressure. A 1 N aqueous hydrochloric acid solution (2.37 mL, 2.37 mmol) and water were added to the resulting residue, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure to obtain 72 mg of the title compound (73%) as a colorless solid.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe resulting organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe insoluble matter was separated by filtration
  6. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-37719abe601a4591a1c32be0b957bdf7
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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