Thionyl Chloride → N-[4-(N,N-Dimethylaminosulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

HRID 1938170Notes

Reaction equation

HRID 1938170 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]([CH3:8])([OH:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.C(N(C(C)C)CC)(C)C.[CH3:24][N:25]([CH3:36])[S:26]([C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1)(=[O:28])=[O:27]>CN(C)C(=O)C.O.N1(C2C=CN=CC=2)CCCC1>[CH3:24][N:25]([CH3:36])[S:26]([C:29]1[CH:35]=[CH:34][C:32]([NH:33][C:4](=[O:5])[C:3]([OH:7])([CH3:8])[C:2]([F:10])([F:9])[F:1])=[CH:31][CH:30]=1)(=[O:27])=[O:28]

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 74369Benzenesulfonamide, 4-amino-N,N-dimethyl-HCID 81531DiisopropylethylamineHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 9862760N-[4-(N,N-Dimethylaminosulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamideYield 37.7%

Reagents, catalysts & solvents 3

HCID 755674-PyrrolidinopyridineCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

To a cooled (-10° C.) solution of α-trifluoromethyl lactic acid (0.69 g) in dry N,N-dimethylacetamide (5 ml) was added thionyl chloride (0.33 ml) dropwise over 2 minutes. The mixture was stirred at -10° C. for 90 minutes, then treated successively with 4-pyrrolidinopyridine (13 mg), di-isopropylethylamine (0.76 ml), and 4-(N,N-dimethylaminosulfonyl)aniline (0.88 g). The reaction mixture was stirred at 22° C. for 48 hours, then diluted with water and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with 1N HCl, brine, dried and the solvent evaporated. The crude product was purified by chromatography (12:1 CH2Cl2 : ethyl acetate) and recrystallised from methyl-t-butyl ether/hexane to give the title compound as a colourless crystalline solid (0.56 g); mp 139°-141° C.; MS: m/z=341(M+1); NMR (250 MHz): 1.60 (s,3), 2.58 (s,6), 7.58 (s,1), 7.69-7.73 (d,2), 8.03-8.06 (d,2). Analysis for C12H15F3N2O4S: Calculated: C, 42.35; H, 4.44; N, 8.23; Found: C, 42.21; H, 4.54; N, 8.15.

Workup

  1. stirringThe reaction mixture was stirred at 22° C. for 48 hours
  2. extractionextracted with ethyl acetate
  3. washThe combined ethyl acetate extracts were washed with 1N HCl, brine
  4. customdried
  5. customthe solvent evaporated
  6. customThe crude product was purified by chromatography (12:1 CH2Cl2 : ethyl acetate)
  7. customrecrystallised from methyl-t-butyl ether/hexane

Sources & evidence

ORD record
ord-781d34e102b247c789a25a3d2887a4e8
Source dataset
uspto-grants-1997_12
Patent number
US05693639

Reaction notes

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