2-Fluoro-6-methoxybenzaldehyde → N-{5-chloro-2-[(2-fluoro-6-methoxy-phenyl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 1898036Notes

Reaction equation

HRID 1898036 reaction equation
Br[C:2]1[C:7]([N:8]([CH2:22][O:23][CH3:24])[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:25])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[F:31][C:32]1[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[C:33]=1[CH:34]=[O:35]>C1COCC1>[Cl:25][C:5]1[CH:6]=[C:7]([N:8]([CH2:22][O:23][CH3:24])[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)(=[O:11])=[O:10])[C:2]([CH:34]([C:33]2[C:36]([O:40][CH3:41])=[CH:37][CH:38]=[CH:39][C:32]=2[F:31])[OH:35])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 27373572-Fluoro-6-methoxybenzaldehydeHCID 57942206N-(2-bromo-5-chloro-pyridin-3-yl)-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418918HCID 178418918, compound

Product 1

HCID 57942520N-{5-chloro-2-[(2-fluoro-6-methoxy-phenyl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of N-(2-Bromo-5-chloro-pyridin-3-yl)-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (459 mg, 1.00 mmol) in anhydrous THF (5 mL) at −10° C. was added 2 M isopropylmagnesium chloride in THF (1.1 mL, 2.2 mmol) and stirred at the same temperature for 30 min. 2-Fluoro-6-methoxy-benzaldehyde (308 mg, 2.00 mmol) was subsequently added in one portion, and the reaction mixture was warmed to room temperature and stirred overnight (18 h). It was then quenched with saturated aqueous NH4Cl (10 mL), and extracted with EtOAc (3×75 mL). The combined extracts were washed with aqueous NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using ethyl acetate-hexane to provide N-{5-chloro-2-[(2-fluoro-6-methoxy-phenyl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide. MS m/z 535.4 (M+H).

Workup

  1. stirringstirred overnight (18 h)
  2. customIt was then quenched with saturated aqueous NH4Cl (10 mL)
  3. extractionextracted with EtOAc (3×75 mL)
  4. washThe combined extracts were washed with aqueous NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-48535341d7c04432bc6f9d2eb0bb434b
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

Loading…