Lithium Hydroxide → Rac-2-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid

HRID 1641838Notes

Reaction equation

HRID 1641838 reaction equation
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]([N:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26]([C:28]3[N:29]=[C:30]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[O:31][C:32]=3[C:33]([F:36])([F:35])[F:34])=[O:27])=[CH:21][CH:20]=2)[CH2:15][CH2:14]1)=[O:12])=[O:5])C.[OH-].[Li+]>C(O)C.O>[C:37]1([C:30]2[O:31][C:32]([C:33]([F:34])([F:35])[F:36])=[C:28]([C:26]([NH:25][C:22]3[CH:23]=[CH:24][C:19]([N:16]4[CH2:17][CH2:18][N:13]([C:11]([CH:7]5[CH2:8][CH2:9][CH2:10][CH:6]5[C:4]([OH:5])=[O:3])=[O:12])[CH2:14][CH2:15]4)=[CH:20][CH:21]=3)=[O:27])[N:29]=2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 66738241Rac-2-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid ethyl ester

Product 1

HCID 66738247Rac-2-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acidYield 28.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of racemic 2-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid ethyl ester (100 mg, 0.171 mmol) in 10 mL ethanol was added a solution of lithium hydroxide (14 mg, 0.342 mmol) in 5 mL water. The reaction mixture was stirred at room temperature for 4 hrs and then heated to 50° C. for 1 hr. The reaction mixture was cooled, diluted with water, and washed with diethyl ether. The pH of the aqueous layer was adjusted to pH 5 with 1N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers were dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography (eluted with ethyl acetate/methylene chloride) to yield rac-2-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid (27 mg, 28%). ES-MS calcd for C28H27F3N4O5 (m/e) 556.54, obsd 557.1 (M+H).

Workup

  1. temperatureheated to 50° C. for 1 hr
  2. temperatureThe reaction mixture was cooled
  3. washwashed with diethyl ether
  4. extractionextracted with ethyl acetate
  5. dry with materialThe ethyl acetate layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography (eluted with ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-7bbf70c97eab4e8f97b1ddf514098c00
Source dataset
uspto-grants-2012_02
Patent number
US08115011B2

Reaction notes

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