2-Fluoro-6-methoxybenzaldehyde → 4-chloro-N-{2-[(2-fluoro-6-methoxyphenyl)-hydroxy-methyl]-5-methyl-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 419033Notes

Reaction equation

HRID 419033 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]([CH3:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[F:32][C:33]1[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH3:42])[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]([O:41][CH3:42])=[CH:38][CH:39]=[CH:40][C:33]=3[F:32])[OH:36])=[N:3][CH:4]=[C:5]([CH3:26])[CH:6]=2)[CH2:23][O:24][CH3:25])(=[O:11])=[O:10])=[CH:13][C:14]=1[C:19]([F:22])([F:21])[F:20]

Participants

5

Reactant 3

HCID 27373572-Fluoro-6-methoxybenzaldehydeHCID 57942173N-(2-bromo-5-methyl-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418918HCID 178418918, compound

Product 1

HCID 579421424-chloro-N-{2-[(2-fluoro-6-methoxyphenyl)-hydroxy-methyl]-5-methyl-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideYield 60.7%

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 (158 mg, 0.33 mmol) in THF (3 mL) under nitrogen atmosphere at −30° C. was added isopropylmagnesium chloride (2 M solution in THF, 0.4 mL, 0.8 mmol) via dropwise addition. The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of 2-fluoro-6-methoxy-benzaldehyde (96.6 mg, 0.63 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 extracts 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-{2-[(2-fluoro-6-methoxyphenyl)-hydroxy-methyl]-5-methyl-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (110 mg) as yellow syrup in 60% yield. ESMS m/z: 549 (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 extracts 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-9362479e18d04d9d8358380200cf69cd
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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