Acetonitrile → (R)-N-(bis(3-(trifluoromethoxy)phenyl)-methylene)-2-methylpropane-2-sulfinamide

HRID 1874161Notes

Reaction equation

HRID 1874161 reaction equation
[C:1](#[N:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[F:12][C:13]([F:41])([F:40])[O:14][C:15]1[CH:16]=[C:17]([C:21]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([O:35][C:36]([F:39])([F:38])[F:37])[CH:30]=2)=[N:22][S@@:23]([C:25]([CH3:28])([CH3:27])[CH3:26])=[O:24])[CH:18]=[CH:19][CH:20]=1.[NH4+].[Cl-]>CCOCC.CCOC(C)=O>[F:39][C:36]([F:37])([F:38])[O:35][C:31]1[CH:30]=[C:29]([C:21]([C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:13]([F:41])([F:40])[F:12])[CH:16]=2)=[N:22][S@@:23]([C:25]([CH3:28])([CH3:27])[CH3:26])=[O:24])[CH:34]=[CH:33][CH:32]=1.[C:1]([CH2:2][C:21]([NH:22][S@@:23]([C:25]([CH3:28])([CH3:27])[CH3:26])=[O:24])([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][C:36]([F:37])([F:38])[F:39])[CH:30]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:13]([F:40])([F:41])[F:12])[CH:16]=1)#[N:3]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 59458920(R)-N-(bis(3-(trifluoromethoxy)phenyl)-methylene)-2-methylpropane-2-sulfinamide

Product 2

HCID 59458920(R)-N-(bis(3-(trifluoromethoxy)phenyl)-methylene)-2-methylpropane-2-sulfinamideHCID 59459074(R)-N-(2-cyano-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

(R)—N-(bis(3-(trifluoromethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide was prepared as described for Procedure 11. Under an argon atmosphere, acetonitrile (0.46 mL, 8.84 mmol, 2.0 eq) was stirred in anhydrous Et2O (40 mL) in an oven-dried round bottomed flask at −78° C. LDA (2.0 M, 4.42 mL, 8.84 mmol, 2.0 eq) was added dropwise. The resulting mixture was stirred at −78° C. for 30 min. (R)—N-(bis(3-(trifluoromethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide (2.0 g, 4.42 mmol) in Et2O (10 mL) was added dropwise to the above stirred solution. The reaction mixture was stirred at −78° C. for 4 h. Sat'd NH4Cl was added, followed by the addition of EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%) to give (R)—N-(2-cyano-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)-2-methylpropane-2-sulfinamide as light tan oil (1.15 g, yield: 52.7% with 0.85 g recovery of the starting material). LC-MS (ESI) 495.26 (M+H), retention time=3.84 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run); 1H NMR (400 MHz, CDCl3) δ ppm 7.40-7.35 (m, 2H), 7.29 (d, J=8 Hz, 1H), 7.21-7.16 (m, 4H), 7.08 (m, 1H), 4.53 (s, 1H), 3.75 (d, J=16 Hz, 1H) 3.56 (d, J=16 Hz, 1H), 1.21 (s, 9H).

Workup

  1. additionwas added dropwise to the above stirred solution
  2. washThe organic layer was washed with H2O and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%)

Sources & evidence

ORD record
ord-01d9e71c0d034d088bdd8eecac7bf0ef
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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