Diethyl Ether → (R)-N-[4-(4-Acetamidophenylsulphonyl)-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2301023Notes

Reaction equation

HRID 2301023 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].[C:17]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[C:32]([Cl:37])[CH:31]=2)(=[O:29])=[O:28])=[CH:23][CH:22]=1)(=[O:19])[CH3:18].CCOCC>C(Cl)Cl.CN(C=O)C>[C:17]([NH:20][C:21]1[CH:22]=[CH:23][C:24]([S:27]([C:30]2[CH:36]=[CH:35][C:33]([NH:34][C:9](=[O:10])[C@:8]([OH:7])([CH3:16])[C:12]([F:15])([F:14])[F:13])=[C:32]([Cl:37])[CH:31]=2)(=[O:29])=[O:28])=[CH:25][CH:26]=1)(=[O:19])[CH3:18]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 65578Oxalyl chlorideHCID 2760712(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acidHCID 222873434-(4-Acetamidophenylsulphonyl)-2-chloroaniline

Product 1

HCID 69749328(R)-N-[4-(4-Acetamidophenylsulphonyl)-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 11%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.047 ml) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (Method 9) (0.077 g) in DCM (2.5 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature for 2 hours and was then added to a solution of 4-(4-acetamidophenylsulphonyl)-2-chloroaniline (Method 10) (0.160 g) in DCM (2.5 ml) and stirred a further 2 hours. Ether (50 ml) was added and the mixture was washed with water (2×50 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 0-70% ethyl acetate/toluene to give the title compound (0.025 g) as a solid. NMR: 1.6 (s, 3H), 2.05 (s, 3H), 7.1-7.3 (brm, 1H), 7.8 (d, 2H), 7.9 (m, 3H), 7 97-8.05 (brs, 2H), 8.25 (d, 1H), 10.36 (brs, 1H); MS (ESP−): 463; EA: found: C, 47.8; H, 3.6; N, 5.4%; C18H16ClF3N2O5S.0.2C7H8 requires: C, 48.2; H, 3.7; N, 5.8%.

Workup

  1. stirringstirred a further 2 hours
  2. washthe mixture was washed with water (2×50 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 0-70% ethyl acetate/toluene

Sources & evidence

ORD record
ord-9dd39116099c4b2193ae2d70a81b41db
Source dataset
uspto-grants-2002_12
Patent number
US06498275B1

Reaction notes

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