2,6-Difluorobenzoyl chloride → N-[1-[4'-[(difluoromethyl)thio][1,1-biphenyl]4-yl]-2-hydroxyethyl]-2,6-difluorobenzamide

HRID 1108154Notes

Reaction equation

HRID 1108154 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].Cl.[NH2:13][CH:14]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([S:29][CH:30]([F:32])[F:31])=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)[CH2:15][OH:16].C(=O)(O)[O-].[Na+]>ClCCl.O>[F:32][CH:30]([F:31])[S:29][C:26]1[CH:25]=[CH:24][C:23]([C:20]2[CH:21]=[CH:22][C:17]([CH:14]([NH:13][C:4](=[O:5])[C:3]3[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:7]=3[F:11])[CH2:15][OH:16])=[CH:18][CH:19]=2)=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 874382,6-Difluorobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 18786426beta-Amino-4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-ethanol hydrochloride salt

Product 1

HCID 18786420N-[1-[4'-[(difluoromethyl)thio][1,1-biphenyl]4-yl]-2-hydroxyethyl]-2,6-difluorobenzamideYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.137 g (0.776 mmol) of 2,6-difluorobenzoyl chloride in 1 mL of dichloromethane was added dropwise to a mixture of 0.23 g (0.693 mmol) of β-amino-4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-ethanol hydrochloride salt, 1.5 mL of dichloromethane, and 1.5 mL of sodium bicarbonate (saturated aqueous solution). The mixture was stirred for 2 h, and was diluted with 10 mL of water. The mixture was extracted with 3×20 mL of dichloromethane, 35 mL of dichloromethane and the organic phase separated. The combined extracts were dried and evaporated. Chromatography on silica gel (eluted with ethyl acetate/hexane (1:1)) gave the product 0.28 g (93% yield) as a white solid m.p. 156.5-157° C. IR(Nujol): 3294, 1649, 1624, 1589, 1535, 1309, 1233, 1071, 1004, 819 cm-1. 1H-NMR(CDCl3): δ2.15 (t, J=5.75 Hz, 1H), 4.03-4.06 (m, 2H), 5.33-5.37 (m, 1H), 6.81 (d, J=7.2 Hz, 1H), 6.86 (t, J=57 Hz, 1H), 6.94-6.99 (m, 2H), 7.35-7.43 (m, 1H), 7.48 (d, J=8 Hz, 2H), 7.50-7.65 (m, 6H).

Workup

  1. extractionThe mixture was extracted with 3×20 mL of dichloromethane, 35 mL of dichloromethane
  2. customthe organic phase separated
  3. customThe combined extracts were dried
  4. customevaporated

Sources & evidence

ORD record
ord-0a9a340fbf6249bd9f89bde904126149
Source dataset
uspto-grants-2000_05
Patent number
US06063932

Reaction notes

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