Water → N-[2-chloro-1-[4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-yl]ethyl]-2,6-difluorobenzamide

HRID 1108161Notes

Reaction equation

HRID 1108161 reaction equation
Cl.[Cl:2][CH2:3][CH:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH:19]([F:21])[F:20])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[NH2:5].[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:24]=1[C:25](Cl)=[O:26].C(=O)(O)[O-].[Na+].O>C(OCC)(=O)C>[Cl:2][CH2:3][CH:4]([NH:5][C:25](=[O:26])[C:24]1[C:23]([F:22])=[CH:31][CH:30]=[CH:29][C:28]=1[F:32])[C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH:19]([F:21])[F:20])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 874382,6-Difluorobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 67563721(+/-)-alpha-(Chloromethyl)-4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-methanamine hydrochloride

Product 1

HCID 18786412N-[2-chloro-1-[4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-yl]ethyl]-2,6-difluorobenzamideYield 85.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a slurry of 1.1 g of (+/-)-α-(chloromethyl)-4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-methanamine hydrochloride in 13 mL of ethyl acetate was added 0.60 g of 2.6-difluorobenzoyl chloride. 0.60 g of sodium bicarbonate, and 3 mL of water. After 15 min, ethyl acetate was added and the organic phase was washed with aqueous NaCl, dried (MgSO4), filtered, and concentrated to dryness. The residue was triturated with toluene/hexanes, filtered, washed with hexanes, and suction-dried to afford 1.22 g of product, m.p. 148-150° C. 1H-NMR (CDCl3): δ4.0 (dq, 2H), 5.6 (m, 1H), 6.75 (br d, 1H), 6.85 (t, 1H, J=60 Hz), 7.0 (t, 2H), 7.4 (m, 1H), 7.5 (d, 2H), 7.6 (m, 6H).

Workup

  1. washthe organic phase was washed with aqueous NaCl
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe residue was triturated with toluene/hexanes
  6. filtrationfiltered
  7. washwashed with hexanes
  8. customsuction-dried

Sources & evidence

ORD record
ord-8d37e74c167340df9974f48328fd2a47
Source dataset
uspto-grants-2000_05
Patent number
US06063932

Reaction notes

Loading…