p-(Difluoromethoxy)benzaldehyde → HCID 88924999, compound

HRID 2279572Notes

Reaction equation

HRID 2279572 reaction equation
[F:1][CH:2]([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1.[CH3:13][C:14]([S@@:17]([NH2:19])=[O:18])([CH3:16])[CH3:15]>C1COCC1.[Cl-].[Na+].O>[F:1][CH:2]([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7](/[CH:8]=[N:19]/[S@:17]([C:14]([CH3:16])([CH3:15])[CH3:13])=[O:18])=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 2736986p-(Difluoromethoxy)benzaldehydeHCID 11355477tert-Butylsulfinamide, (S)-(-)-

Product 1

HCID 88924999HCID 88924999, compoundYield 100.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 4-(difluoromethoxy)benzaldehyde (10 g, 58 mmol) and (S)-2-methylpropane-2-sulfinamide (13 g, 105 mmol) in THF (50 mL) was added Ti(OEt)4 (43 mL, 209 mmol) and the reaction was stirred at RT overnight. The mixture was poured into brine (400 mL) and stirred for 10 min, filtered, and the filtered solids rinsed with additional THF/EtOAc. The organic layer was separated, and the aqueous layer extracted with additional EtOAc. The combined extracts were washed with brine, dried (MgSO4), and concentrated. The residue was dry loaded and passed through a SiO2 plug eluting with a EtOAc/hexane gradient (10 to 15% EtOAc) to afford 16 g (100%) of (S,E)-N-(4-(difluoromethoxy)benzylidene)-2-methylpropane-2-sulfinamide (378) as pale yellow liquid.

Workup

  1. stirringstirred for 10 min
  2. filtrationfiltered
  3. washthe filtered solids rinsed with additional THF/EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with additional EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was dry
  10. washeluting with a EtOAc/hexane gradient (10 to 15% EtOAc)

Sources & evidence

ORD record
ord-ee56c2d3b58f4f9fb889abd0414e5a10
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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