Oxalyl chloride → (R)-N-[2-Bromo-4-(phenylthio)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 841194Notes

Reaction equation

HRID 841194 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].[Br: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(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>ClCCl.CN(C=O)C>[Br: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 65578Oxalyl chlorideHCID 685102,6-Di-tert-butylpyridineHCID 2760712(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acidHCID 226212822-Bromo-4-phenylthioaniline

Product 1

HCID 69118141(R)-N-[2-Bromo-4-(phenylthio)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 30.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.052 ml) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (Method 9) (0.095 g) in dichloromethane (3 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature for 2 hours and was then added to a solution of 2-bromo-4-phenylthioaniline (Method 17) (0.135 g) and 2,6-di-tert-butylpyridine (0.14 ml) in dichloromethane (5 ml) and stirred a further 3 hours. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 0-30% ethyl acetate/hexane to give the title compound (0.061 g) as a waxy solid. NMR: 1.59 (s, 3H), 7.25-7.50 (bm, 6H), 7.59 (s, 1H), 7.82 (bs, 1H), 7.98 (d,1H), 9.79 (s, 1H); MS: 420 (M−H)−.

Workup

  1. stirringstirred a further 3 hours
  2. customVolatile material was removed by evaporation
  3. customthe residue was purified by chromatography on a silica gel Mega Bond Elut column
  4. washeluting with 0-30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-7741708ff35043a1b71c1c5765b052fe
Source dataset
uspto-grants-2002_04
Patent number
US06369273B1

Reaction notes

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