Ethyl Acetate → (R)-N-[2-Chloro-4-(phenylthio)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 841189Notes

Reaction equation

HRID 841189 reaction equation
C(Cl)(=O)C(Cl)=O.[OH:7][C@@:8]([CH3:16])([C:12]([F:15])([F:14])[F:13])[C:9](O)=[O:10].[Cl:17][C:18]1[CH:24]=[C:23]([S:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:22]=[CH:21][C:19]=1[NH2:20].C(OCC)(=O)C>ClCCl.CN(C=O)C>[Cl:17][C:18]1[CH:24]=[C:23]([S:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:22]=[CH:21][C:19]=1[NH:20][C:9](=[O:10])[C@:8]([OH:7])([CH3:16])[C:12]([F:15])([F:14])[F:13]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 2760712(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acidHCID 222872082-Chloro-4-phenylthioaniline

Product 1

HCID 54234104(R)-N-[2-Chloro-4-(phenylthio)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 67.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.063 ml) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (Method 9) (0.106 g) in dichloromethane (2 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature for 90 minutes and was then added to a solution of 2-chloro-4-phenylthioaniline (Method 11) (0.143 g) in dichloromethane (4 ml) and stirred a further 3 hours. Ethyl acetate (30 ml) was added and the mixture was washed with water (2×30 ml) and brine then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 15% ethyl acetate/hexane to give the title compound (0.153 g) as a gum. NMR: 1.57 (s, 3H), 7.26-7.41 (m, 6H), 7.44 (d, 1H), 7.82 (s, 1H), 7.95 (d, 1H), 9.74 (s, 1H); MS: 374 (M−H)−.

Workup

  1. stirringstirred a further 3 hours
  2. washthe mixture was washed with water (2×30 ml) and brine
  3. customthen dried
  4. customVolatile material was removed by evaporation
  5. customthe residue was purified by chromatography on a silica gel Mega Bond Elut column
  6. washeluting with 15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-01949835eced4260b10ce687e3d82b80
Source dataset
uspto-grants-2002_04
Patent number
US06369273B1

Reaction notes

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