Ammonium Hydroxide → (S)-3-Amino-4,4,4-trifluoro-1-p-tolyl-3-(4-(4,4,4-trifluorobutoxy)phenyl)-butan-1-one

HRID 1629760Notes

Reaction equation

HRID 1629760 reaction equation
[F:1][C:2]([F:29])([F:28])/[C:3](/[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:16][CH:15]=1)=[CH:4]\[C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1)=[O:6].[NH4+:30].[OH-]>CS(C)=O.CCOC(C)=O>[NH2:30][C@@:3]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([F:25])([F:26])[F:27])=[CH:16][CH:15]=1)([C:2]([F:28])([F:29])[F:1])[CH2:4][C:5]([C:7]1[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=1)=[O:6]

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 86685850HCID 86685850, compound

Product 1

HCID 86685849(S)-3-Amino-4,4,4-trifluoro-1-p-tolyl-3-(4-(4,4,4-trifluorobutoxy)phenyl)-butan-1-oneYield 101%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Intermediate 2E (2.1 g, 5.04 mmol) in DMSO (50 mL) was added 15 N aq NH4OH (25 mL). The mixture was stirred in sealed pressure vessel for 2 days. The reaction was diluted with EtOAc (60 mL), washed with water and sat'd aq NaCl, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography column (eluted with EtOAc in hexanes to provide racemic Intermediate 2F (2.2 g, 101%) as a white solid. LCMS Anal. Calc'd for C21H21F6NO2 433.39, found [M+H] 434.2. Separation of the individual enantiomers of Intermediate 2F was carried out using preparative chiral SFC method A: Racemic Intermediate 2F (2200 mg) provided Intermediate 2F, isomer 1 (817 mg) and Intermediate 2F, isomer 2 (790 mg). Enantiomeric purity determination of Intermediate 2F, isomer 1 and 2 was carried out using analytical SFC method A. Intermediate 2F, isomer 1: RT=2.2 min, 99% ee. Intermediate 2F, isomer 2: RT=2.8 min, 99% ee. X-ray crystal data collected for the camphorsulfonic acid salt of Intermediate 2F, isomer 1 showed the chiral center to have the R-configuration; therefore, the chiral center for Intermediate 2F, isomer 2 has the S-configuration.

Workup

  1. washwashed with water
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography column (
  6. washeluted with EtOAc in hexanes

Sources & evidence

ORD record
ord-6696cc0897d948a494cc0b889cb24774
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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