2-Chloro-6-fluorobenzaldehyde → 4-chloro-N-{5-chloro-2-[(2-chloro-6-fluoro-phenyl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 419034Notes

Reaction equation

HRID 419034 reaction equation
Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5](C)=[CH:4][N:3]=1.C([Mg][Cl:31])(C)C.[Cl:32][C:33]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:34]=1[CH:35]=[O:36]>C1COCC1>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([N:8]([C:7]2[C:2]([CH:35]([C:34]3[C:37]([F:41])=[CH:38][CH:39]=[CH:40][C:33]=3[Cl:32])[OH:36])=[N:3][CH:4]=[C:5]([Cl:31])[CH:6]=2)[CH2:23][O:24][CH3:25])(=[O:10])=[O:11])=[CH:13][C:14]=1[C:19]([F:20])([F:21])[F:22]

Participants

5

Reactant 3

HCID 678472-Chloro-6-fluorobenzaldehydeHCID 57942173N-(2-bromo-5-methyl-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418918HCID 178418918, compound

Product 1

HCID 579420944-chloro-N-{5-chloro-2-[(2-chloro-6-fluoro-phenyl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(2-bromo-5-methyl-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (246 mg, 0.5 mmol) in THF (3 mL) under nitrogen atmosphere at −30° C. was added isopropylmagnesium chloride (2 M solution in THF, 0.6 mL, 1.2 mmol) via dropwise addition. The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of 2-chloro-6-fluoro-benzaldehyde (150.6 mg, 0.95 mmol) at −30° C. The mixture was stirred at room temperature for 3 h, quenched with saturated aqueous NH4Cl solution (5 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL) and brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (30% EtOAc-hexanes) to obtain 4-chloro-N-{5-chloro-2-[(2-chloro-6-fluoro-phenyl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (144 mg) as yellow syrup in 51% yield. MS m/z 573 (M+H).

Workup

  1. additionvia dropwise addition
  2. stirringThe mixture was stirred at room temperature for 3 h
  3. customquenched with saturated aqueous NH4Cl solution (5 mL)
  4. extractionextracted with EtOAc (2×25 mL)
  5. washThe combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL) and brine (25 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by flash column chromatography on silica gel (30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-c68fa02d813b4a41a198505706481406
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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