tert-Butylsulfinamide, (R)-(+)- → HCID 90301392, compound

HRID 627647Notes

Reaction equation

HRID 627647 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH3:10])[C:5]([F:8])=[N:6][CH:7]=1.[CH3:12][C:13]([S@:16]([NH2:18])=[O:17])([CH3:15])[CH3:14]>C1COCC1.[Cl-].[Na+].O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:1][C:2]1[CH:3]=[C:4](/[C:9](=[N:18]\[S@@:16]([C:13]([CH3:15])([CH3:14])[CH3:12])=[O:17])/[CH3:10])[C:5]([F:8])=[N:6][CH:7]=1

Participants

6

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 401519061-(5-Bromo-2-fluoropyridin-3-yl)ethan-1-one

Product 1

HCID 90301392HCID 90301392, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 1-(5-bromo-2-fluoropyridin-3-yl)ethanone (11 g, 51 mmol), (R)-2-methylpropane-2-sulfinamide (12.2 g, 101 mmol) and titanium (IV) ethoxide (26.1 mL, 126 mmol) in THF (100 mL) was heated to reflux for 2 h. The mixture was cooled to room temperature, brine was added and the mixture was stirred for 10 min. The suspension was filtered through silica gel. The organic phase was separated and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (eluted with 0-20% EtOAc/hexanes) gave (R,Z)—N-(1-(5-bromo-2-fluoropyridin-3-yl)ethylidene)-2-methylpropane-2-sulfinamide (16 g, 50 mmol, 99% yield) as a bright yellow oil. LC/MS (ESI) m/z=321 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. filtrationThe suspension was filtered through silica gel
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography on silica gel (eluted with 0-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6986b2dbdb43488c8b238cf07c34d92d
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…