Thionyl Chloride → N-[4-(Phenylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamide

HRID 327214Notes

Reaction equation

HRID 327214 reaction equation
[F:1][CH:2]([F:11])[C:3]([CH:8]([F:10])[F:9])([OH:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[C:16]1([S:22]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.O>[C:16]1([S:22]([C:25]2[CH:26]=[CH:27][C:28]([NH:29][C:4](=[O:5])[C:3]([OH:7])([CH:8]([F:10])[F:9])[CH:2]([F:11])[F:1])=[CH:30][CH:31]=2)(=[O:23])=[O:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 5166664-(Phenylsulfonyl)anilineHCID 516892Sodium BicarbonateHCID 222874542,2-Bis-difluoromethyl-2-hydroxyacetic acid

Product 1

HCID 21480121N-[4-(Phenylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamideYield 57.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 2,2-bis-difluoromethyl-2-hydroxyacetic acid (0.5 g, 2.84 mmoles) in dimethylacetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmoles) dropwise. The resulting solution was stirred at -10° C. for approximately 30 mins. 4-(Phenylsulfonyl) aniline (0.58 g, 2.5 mmoles) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into water, sodium bicarbonate solution added to give a pH of 7 and extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with water, brine, dried (Na2SO4), decolorized (charcoal), and evaporated. The crude solid was dissolved in ether, clarified by filtration, and evaporated. Crystallization from methanol/water gave the title compound (0.56 g, 57%) as white, silky needles; mp 105°-108° C. 1H--NMR (300 MHz, d6 --DMSO) 6.44 (t, J=53.94Hz, 2H, HCF2), 7.58-7.68(m, 3H, ArH), 7.92-8.01 (m, 7H, ArH, OH), 10.51 (s, 1H, NH). MS(CI,CH4):392 (M+1, 100%).

Workup

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. additionadded
  3. customto give a pH of 7
  4. extractionextracted with ethyl acetate
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. dissolutionThe crude solid was dissolved in ether
  9. filtrationclarified by filtration
  10. customevaporated
  11. customCrystallization from methanol/water

Sources & evidence

ORD record
ord-c27f35bc27844142a5753d935c3e99c7
Source dataset
uspto-grants-1993_12
Patent number
US05272163

Reaction notes

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