Acetic Acid → (3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-(2-thiophen-2-yl-propyl)-amino]-propoxy}-phenyl)-acetic acid hydrochloride salt

HRID 902684Notes

Reaction equation

HRID 902684 reaction equation
C[O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[C:26]=2[Cl:35])[CH2:16][CH:17]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)[CH3:18])[CH:6]=1.[Li+].[OH-].CC(O)=O.C(OCC)(=O)C>C1COCC1.O>[ClH:35].[Cl:35][C:26]1[C:27]([C:31]([F:34])([F:32])[F:33])=[CH:28][CH:29]=[CH:30][C:25]=1[CH2:24][N:15]([CH2:16][CH:17]([C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[CH3:18])[CH2:14][CH2:13][CH2:12][O:11][C:7]1[CH:6]=[C:5]([CH2:4][C:3]([OH:36])=[O:2])[CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3939Lithium Hydroxide2×HCID 8857Ethyl AcetateHCID 69253058(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-(2-thiophen-2-yl-propyl)-amino]-propoxy}-phenyl)-acetic Acid Methyl Ester

Product 1

HCID 69253079(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-(2-thiophen-2-yl-propyl)-amino]-propoxy}-phenyl)-acetic acid hydrochloride saltYield 106.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-(2-thiophen-2-yl-propyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester (25 mg, 0.05 mmol) in THF (9 ml) and water (6 ml) was treated with aqueous LiOH (1.0 N, 0.29 ml, 1.0 mmol). After stirring at room temperature for 2 h, additional LiOH (0.29 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 layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacco. The crude mixture was purified by HPLC to give the free amine of title compound as an oil (15 mg, 58%). MS m/e 520.2 (M+H)+. To a solution of the free amine in diethyl ether was added HCl in diethyl ether (1.0M) to precipitate 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. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacco
  8. customThe crude mixture was purified by HPLC

Sources & evidence

ORD record
ord-5cce173a04f64fe79288567cca996507
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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