Methane → N-[4-(Phenylsulfonyl)phenyl]-3,3,-difluoro-2-hydroxy-2-methylpropanamide

HRID 2259673Notes

Reaction equation

HRID 2259673 reaction equation
[OH:1][C:2]([CH:7]([F:9])[F:8])([CH3:6])[C:3](O)=[O:4].S(Cl)(Cl)=O.[C:14]1([S:20]([C:23]2[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+].C>CC(N(C)C)=O>[C:14]1([S:20]([C:23]2[CH:24]=[CH:25][C:26]([NH:27][C:3](=[O:4])[C:2]([OH:1])([CH3:6])[CH:7]([F:9])[F:8])=[CH:28][CH:29]=2)(=[O:21])=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 5

HCID 297MethaneHCID 24386Thionyl ChlorideHCID 25517Ammonium ChlorideHCID 5166664-(Phenylsulfonyl)anilineHCID 147860322-(Difluoromethyl)-2-hydroxypropionic acid

Product 1

HCID 21480134N-[4-(Phenylsulfonyl)phenyl]-3,3,-difluoro-2-hydroxy-2-methylpropanamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of 2-hydroxy-2-difluoromethylpropionic acid (0.9 g, 6.4 mmol) in dry dimethylacetamide (15 ml) was stirred under a nitrogen atmosphere at -10° C. Thionyl chloride (0.76 g, 6.4 mmol) was added and the resulting mixture was allowed to stir at -10° C. for 1 hour. 4-Phenylsulfonylaniline (1.0 g, 4.3 mmol) was then added and the reaction mixture was stirred at -10° C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured into ammonium chloride solution and extracted with ethyl acetate. The combined ethyl acetate fractions were washed with water and brine. After drying (Na2SO4) and decolorization (Charcoal) the solution was evaporated in vacuo. A foam was obtained which was triturated with toluene and crystallized from ethyl acetate/hexane to give the title tertiary carbinol (0.72 g, 47%) as white crystals; mp=168°-169° C. 1H-NMR (300 MHz, d6 -DMSO): 1.41 (s, 3H, CH3), 6.13 (t, J=54.9 Hz, 1H, CHF2), 6.76 (s, 1H, OH), 7.58-7.68 (m, 3H, ArH), 7.89-8.01 (m, 6H, ArH), 10.27 (s, 1H, NH). MS (CI, CH4): 356(M+1, 100). Analysis for C16H15F2NO4S: Calculated: C, 54.08; H, 4.25; N, 3.94 Found: C, 53.75; H, 4.40; N, 3.78

Workup

  1. stirringthe reaction mixture was stirred at -10° C. for a further 15 mins
  2. temperatureto warm to room temperature where it
  3. stirringwas stirred overnight
  4. extractionextracted with ethyl acetate
  5. washThe combined ethyl acetate fractions were washed with water and brine
  6. dry with materialAfter drying (Na2SO4) and decolorization (Charcoal) the solution
  7. customwas evaporated in vacuo
  8. customA foam was obtained which
  9. customwas triturated with toluene
  10. customcrystallized from ethyl acetate/hexane
  11. customto give the title tertiary carbinol (0.72 g, 47%) as white crystals

Sources & evidence

ORD record
ord-51a22f84513449d9b03a08ceafea5129
Source dataset
uspto-grants-1995_12
Patent number
US05474999

Reaction notes

Loading…