Thionyl Chloride → N-[4-[(Methylphenylamino)sulfonyl]phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 1938172Notes

Reaction equation

HRID 1938172 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:15]1([N:21]([CH3:32])[S:22]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C)C(=O)C.O>[F:1][C:2]([F:10])([F:9])[C:3]([OH:7])([CH3:8])[C:4]([NH:29][C:28]1[CH:30]=[CH:31][C:25]([S:22]([N:21]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:32])(=[O:24])=[O:23])=[CH:26][CH:27]=1)=[O:5]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 3085904-amino-N-methyl-N-phenylbenzenesulfonamideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 9930941N-[4-[(Methylphenylamino)sulfonyl]phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 60.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (-20° C.) solution of α-trifluoromethyl lactic acid 0.20 g in dry N,N-dimethylacetamide (4 ml) was added thionyl chloride (0.16 g). The reaction mixture was stirred for 1 hour, then warmed to 0° C. over 30 minutes and treated with 4-(N-phenyl-N-methylaminosulfonyl)aniline (0.34 g). After stirring at 22° C. for 24 hours, the reaction mixture was diluted with water (30 ml) and extracted with ethyl acetate (2×20 ml). The combined ethyl acetate extracts were washed with brine, dried (Na2SO4) and concentrated at reduced pressure to give an oil which was purified by chromatography (1:1 hexane: ethyl aceate) and recrystallised from methyl-t-butyl ether/hexane to produce the title compound as a colourless solid (0.31 g); mp 147°-149° C.; MS: m/z=403(M+1); NMR (250 MHz): 1.55 (s,3), 3.09 (s,3), 7.05-7.08 (m, 2), 7.28-7.43 (m,5), 7.53 (s,1), 7.91-7.95 (m,2), 10.36 (broad s, 1). Analysis for C17H17F3N2O4S: Calculated: C, 50.78; H, 4.26; N, 6.97; Found: C, 50.80; H, 4.37; N, 6.93.

Workup

  1. stirringAfter stirring at 22° C. for 24 hours
  2. extractionextracted with ethyl acetate (2×20 ml)
  3. washThe combined ethyl acetate extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated at reduced pressure
  6. customto give an oil which
  7. customwas purified by chromatography (1:1 hexane: ethyl aceate)
  8. customrecrystallised from methyl-t-butyl ether/hexane

Sources & evidence

ORD record
ord-c8596caa1ea445f49483b85fff756c5e
Source dataset
uspto-grants-1997_12
Patent number
US05693639

Reaction notes

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