Acetic Acid → (3-{(r)-3-[(2-Chloro-3-trifluoromethyl-benzyl)-((s)-2-phenyl-propyl)-amino]-butoxy}-phenyl)-acetic acid hydrochloride salt

HRID 902674Notes

Reaction equation

HRID 902674 reaction equation
C[O:2][C:3](=[O:38])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][C@H:14]([N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[C:28]=2[Cl:37])[CH2:17][C@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:19])[CH3:15])[CH:6]=1.[Li+].[OH-].CC(O)=O.C(OCC)(=O)C>C1COCC1.O>[ClH:37].[Cl:37][C:28]1[C:29]([C:33]([F:34])([F:35])[F:36])=[CH:30][CH:31]=[CH:32][C:27]=1[CH2:26][N:16]([CH2:17][C@H:18]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH3:19])[C@H:14]([CH3:15])[CH2:13][CH2:12][O:11][C:7]1[CH:6]=[C:5]([CH2:4][C:3]([OH:38])=[O:2])[CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3939Lithium Hydroxide2×HCID 8857Ethyl AcetateHCID 69252464(3-{(R)-3-[(2-Chloro-3-trifluoromethyl-benzyl)-((S)-2-phenyl-propyl)-amino]-butoxy}-phenyl)-acetic Acid Methyl Ester

Product 1

HCID 69254319(3-{(r)-3-[(2-Chloro-3-trifluoromethyl-benzyl)-((s)-2-phenyl-propyl)-amino]-butoxy}-phenyl)-acetic acid hydrochloride saltYield 140.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of compound (3-{(R)-3-[(2-Chloro-3-trifluoromethyl-benzyl)-((S)-2-phenyl-propyl)-amino]-butoxy}-phenyl)-acetic acid methyl ester (50 mg, 0.1 mmol) in THF (9 ml) and water (6 ml) was treated with aqueous LiOH (1.0 N, 1.0 ml, 1.0 mmol). After stirring at room temperature for 2 h, additional LiOH (1.0 ml, 1.0 mmol) was added and stirring was continued for 2 h. The reaction was neutralized with AcOH and poured into water and ethyl acetate. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacco. The crude mixture was purified by HPLC (YMC CombiPrep ODS-A, 50×20 mm, 20 mL/min, A: acetonitrile B: water, A: 60 to 100% during 10 min, v detection at 254 nm) to give the free acid of title compound as an oil (40 mg, 75%). MS m/e 534.2 (M+H)+. To a solution of the free amine in diethyl ether was added HCl in diethyl ether (1.0M) to precipitate the HCl salt. The suspension was filtered and dried to give the title compound as a white solid.

Workup

  1. stirringstirring
  2. waitwas continued for 2 h
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacco
  7. customThe crude mixture was purified by HPLC (YMC CombiPrep ODS-A, 50×20 mm, 20 mL/min
  8. waitA: acetonitrile B: water, A: 60 to 100% during 10 min

Sources & evidence

ORD record
ord-1e84e6bd5eda4290b6daadc0f82c7a80
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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