Ethylacetate heptane → (R)-2-methyl-N-[(1S)-1-[4-(trifluoromethoxy)phenyl]ethyl]propane-2-sulfinamide

HRID 57468Notes

Reaction equation

HRID 57468 reaction equation
[CH3:1][C:2]([S@:5](/[N:7]=[CH:8]/[C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=1)=[O:6])([CH3:4])[CH3:3].[CH3:20][Mg]Br.CCOC(C)=O.CCCCCCC>C(Cl)Cl.CCOCC>[CH3:4][C:2]([S@:5]([NH:7][C@H:8]([C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:17])([F:18])[F:19])=[CH:11][CH:10]=1)[CH3:20])=[O:6])([CH3:1])[CH3:3]

Participants

6

Reactant 3

HCID 21899848Ethylacetate heptaneHCID 90416044(NE,R)-2-methyl-N-[[4-(trifluoromethoxy)phenyl]methylidene]propane-2-sulfinamideHCID 178418573HCID 178418573, compound

Product 1

HCID 90416158(R)-2-methyl-N-[(1S)-1-[4-(trifluoromethoxy)phenyl]ethyl]propane-2-sulfinamideYield 62%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R,E)-2-methyl-N-(4-(trifluoromethoxy)benzylidene)propane-2-sulfinamide (7.7 g, 26.3 mmol) in CH2Cl2 (150 mL), cooled to 0° C. (water/ice bath), under nitrogen, was added 3M methyl magnesium bromide (35 mL, 105 mmol) in Et2O. The reaction mixture was stirred at 0° C. for 30 min, then allowed to warm up to room temperature and stirred additional 4 hrs. The reaction mixture was cooled again to 0° C. and quenched with the slow addition of a saturated NH4Cl solution. The by-phasic mixture was diluted with DCM and Water and the aqueous extracted with DCM two times. The organic phases were combined, washed with brine, dried (Na2SO4), filtered and concentrated to 11.5 g crude white solid. Silica gel column chromatography (EtOAc/Heptane 0 to 30%) afforded (R)-2-methyl-N—((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)propane-2-sulfinamide (5.08 g, 16.2 mmol, 62% yield) as a white crystalline solid. 1H NMR (400 MHz, CDCl3) δ 1.21 (s, 9H) 1.53 (d, J=6.70 Hz, 3H) 3.31 (d, J=2.74 Hz, 1H) 4.59 (qd, J=6.67, 3.37 Hz, 1H) 7.18 (d, J=8.02 Hz, 2H) 7.36 (d, J=8.66 Hz, 2H). LCMS m/z 310.2 (M+H)+, Rt 0.90 min.

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred additional 4 hrs
  3. temperatureThe reaction mixture was cooled again to 0° C.
  4. customquenched with the slow addition of a saturated NH4Cl solution
  5. additionThe by-phasic mixture was diluted with DCM and Water
  6. extractionthe aqueous extracted with DCM two times
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated to 11.5 g crude white solid

Sources & evidence

ORD record
ord-7971b0bb989e4adcb2eccdde260e475b
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

Loading…