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 1898040Notes

Reaction equation

HRID 1898040 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-e7313c245b7047c1a48b1d1c89cd3b40
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

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