Citric Acid → 2-(2-fluoro-pyridin-4-yl)-2-(N-acetyl-cyclopentylamino)-1-(3-trifluoromethyl-phenyl)-ethanol

HRID 1533110Notes

Reaction equation

HRID 1533110 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH:8]([NH:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[OH:10])[CH:5]=[CH:4][N:3]=1.C(NC(C)C)(C)C.[C:34](Cl)(=[O:36])[CH3:35].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([CH:8]([N:21]([CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[C:34](=[O:36])[CH3:35])[CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:19])([F:20])[F:18])[CH:12]=2)[OH:10])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 6367Acetyl chlorideHCID 7912DiisopropylamineHCID 155242522-(2-Fluoro-pyridin-4-yl)-2-cyclo-pentylamino-1-(3-trifluoromethyl-phenyl)-ethanol

Product 1

HCID 155242532-(2-fluoro-pyridin-4-yl)-2-(N-acetyl-cyclopentylamino)-1-(3-trifluoromethyl-phenyl)-ethanol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A stirred solution of 2-(2-fluoro-pyridin-4-yl)-2-cyclopentylamino-1-(3-trifluoromethyl-phenyl)-ethanol (6) (1.0 g, 2.7 mmol) and diisopropylamine (0.95 mL, 5.4 mmol) in methylene chloride (10 mL) was placed under argon and cooled to −10° C. Acetyl chloride (0.21 mL, 3.0 mmol) in methylene chloride (1.0 mL) was slowly added to the reaction mixture. After 2 hrs, ethyl acetate was added (200 mL) followed by aqueous citric acid (50 mL of a 10% solution). The organic layer was then washed with aqueous sodium bicarbonate (50 mL of a sat. solution) and water (50 mL), dried (sodium sulfate), filtered, and concentrated. The crude residue was passed though a pad a silica gel (50% ethyl acetate in hexane) to remove minor impurities, and taken to the next step. Colorless oil (95%): 1H NMR (300 MHz, CDCl3) d 8.54 (d, J=5.1 Hz, 1 H, Pyr), 7.49 (m, 4 H, Ar), 6.81 (d, J=5.0 Hz, 1 H, Pyr), 6.72 (s, 1 H, Pyr), 5.63 (s, 1 H, OH), 5.46 (s, 1 H, PhCHOH), 4.34 (s, 1 H, CHCHN), 4.16 (m, 1 H, CH2CHCH2), 2.32 (s, 3 H, COCH3), 1.90 (m, 1 H, CH2), 1.60 (m, 7 H, CH2).

Workup

  1. washThe organic layer was then washed with aqueous sodium bicarbonate (50 mL of a sat. solution) and water (50 mL)
  2. dry with materialdried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto remove minor impurities

Sources & evidence

ORD record
ord-2aadbe33bbae4c67b7946ed8e660251d
Source dataset
uspto-grants-2001_03
Patent number
US06207687B1

Reaction notes

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