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

HRID 238735Notes

Reaction equation

HRID 238735 reaction equation
CC(OC)=O.[Li+].[CH3:7][CH:8]([N-:10]C(C)C)C.[F:14][C:15]([F:43])([F:42])[O:16][C:17]1[CH:18]=[C:19]([C:23]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]([F:41])([F:40])[F:39])[CH:32]=2)=[N:24][S@@:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[CH:20]=[CH:21][CH:22]=1.[NH4+].[Cl-]>CCOCC.CCOC(C)=O>[F:41][C:38]([F:39])([F:40])[O:37][C:33]1[CH:32]=[C:31]([C:23]([C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([O:16][C:15]([F:43])([F:42])[F:14])[CH:18]=2)=[N:24][S@@:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[CH:36]=[CH:35][CH:34]=1.[C:8]([CH2:7][C:23]([NH:24][S:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])([C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([O:16][C:15]([F:14])([F:42])[F:43])[CH:18]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]([F:41])([F:40])[F:39])[CH:32]=1)#[N:10]

Participants

8

Reactant 4

HCID 6584Methyl AcetateHCID 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 72291138HCID 72291138, compound

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, CH3COOMe (0.70 mL, 8.83 mmol, 2.0 eq) was stirred in anhydrous Et2O (50 mL) in an oven-dried round bottomed flask at −78° C. LDA (2.0 M, 4.4 mL, 8.8 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 1.5 h. Saturated 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 N-(2-cyano-1,1-bis(3-(trifluoromethoxy)phenyl)-ethyl)-2-methylpropane-2-sulfinamide as light tan oil (1.96 g, yield: 84.1%). LC-MS (ESI) 528.34 (M+H), retention time=4.00 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run); 1H NMR (400 MHz, CDCl3) δ ppm 7.36 (d, J=8.0 Hz, 2H), 7.31 (t, J=8.0 Hz, 1H), 7.25-7.18 (m, 2H), 7.14-7.05 (m, 3H), 6.14 (s, 1H), 3.93 (d, J=16.1 Hz, 1H), 3.54 (d, J=15.9 Hz, 1H), 3.86 (m, 2H), 3.49 (s, 3H), 1.26 (s, 9H). 13C NMR (400 MHz, CDCl3) ppm 22.71, 43.84, 51.68, 56.41, 63.69, 118.63, 119.52, 120.49, 121.35, 124.27, 125.73, 129.81, 129.92, 143.83, 147.52, 149.33, 171.93.

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-693b7de1fd6544ff8f8ca31d42ad709c
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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