Hydrochloric Acid → {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid

HRID 1894480Notes

Reaction equation

HRID 1894480 reaction equation
C[O:2][C:3](=[O:47])[CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([N:13]2[C@@:17]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)([CH3:18])[C@@:16]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)([CH3:26])[N:15]=[C:14]2[C:34]2[CH:35]=[N:36][C:37]([C:43]([CH3:46])([CH3:45])[CH3:44])=[CH:38][C:39]=2[O:40][CH2:41][CH3:42])=[O:12])[CH2:7][CH2:6]1.[OH-].[Li+].Cl>CO.O1CCCC1.O>[C:43]([C:37]1[N:36]=[CH:35][C:34]([C:14]2[N:13]([C:11]([N:8]3[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:47])=[O:2])[CH2:10][CH2:9]3)=[O:12])[C@@:17]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)([CH3:18])[C@@:16]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)([CH3:26])[N:15]=2)=[C:39]([O:40][CH2:41][CH3:42])[CH:38]=1)([CH3:44])([CH3:45])[CH3:46]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 57670154{1-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid methyl ester

Product 1

HCID 57670162{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acidYield 94.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

{1-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid methyl ester (519 mg, 0.763 mmole, example 162) in methanol (4 mL) and tetrahydrofuran (4 mL) was treated with lithium hydroxide (36 mg) in water (4 mL) and allowed to stir at room temp. for 3 h. The mixture was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate. The solids were filtered off, and the filtrate was concentrated to give {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid (482 mg) which was used without purification.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe solids were filtered off
  5. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-84509096baf145c397d830acb8532948
Source dataset
uspto-grants-2013_08
Patent number
US08513239B2

Reaction notes

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