Thionyl Chloride → 3,3,3-trifluoro-N-(4-flurosulfonylphenyl)-2-hydroxy-2-methylpropanamide

HRID 1938167Notes

Reaction equation

HRID 1938167 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.[S:15]([F:25])(=[O:24])([C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1)=[O:16]>CN(C)C(=O)C.O>[F:1][C:2]([F:10])([F:9])[C:3]([OH:7])([CH3:8])[C:4]([NH:23][C:20]1[CH:21]=[CH:22][C:17]([S:15]([F:25])(=[O:24])=[O:16])=[CH:18][CH:19]=1)=[O:5]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 668234-Aminobenzenesulfonyl fluorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 105914083,3,3-trifluoro-N-(4-flurosulfonylphenyl)-2-hydroxy-2-methylpropanamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-20 °C

Procedure

To a cooled (-20° C.) solution of α-trifluoromethyl lactic acid (2.0 g) in dry N,N-dimethylacetamide (15 ml) was added thionyl chloride (0.97 mL) dropwise over 10 minutes. The reaction mixture was stirred at -20° C. for 1 hour, warmed to 0° C. over 1 hour, then treated with sulfanilyl fluoride (2.22 g) in one portion and heated at 100° C. for 24 hours. After cooling to 22° C. the reaction mixture was diluted with water (150 ml) and extracted with ethyl acetate (3×35 ml). The combined organic extracts were washed with water, brine, dried and the solvent removed under reduced pressure. The crude product was purified by chromatography (13:1 CH2Cl2 :Et2 0) and recrystallised from methyl-t-butyl ether to give 3,3,3-trifluoro-N-[4-(fluorosulfonyl)phenyl]-2-hydroxy-2-methylpropanamide as colourless crystals, (1.7 g); mp 152°-154° C.; MS: m/z=316(M+1); NMR (CDCl3): 1.78 (s,3), 3.51 (broad s), 7.86-7.89 (m, 2), 7.99-8.03 (m,2), 8.79 (broad s,1). Analysis for C10H9 F4NO4S: Calculated: C, 38.10; H,2.88; N, 4.44; Found: C, 38.21; H, 2.97; N, 4.44.

Workup

  1. temperaturewarmed to 0° C. over 1 hour
  2. temperatureheated at 100° C. for 24 hours
  3. temperatureAfter cooling to 22° C. the reaction mixture
  4. extractionextracted with ethyl acetate (3×35 ml)
  5. washThe combined organic extracts were washed with water, brine
  6. customdried
  7. customthe solvent removed under reduced pressure
  8. customThe crude product was purified by chromatography (13:1 CH2Cl2 :Et2 0)
  9. customrecrystallised from methyl-t-butyl ether

Sources & evidence

ORD record
ord-842f8cae4aa441c1ad17215c3119f2f1
Source dataset
uspto-grants-1997_12
Patent number
US05693639

Reaction notes

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