(NE,R)-2-methyl-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methylidene]propane-2-sulfinamide → (R)-2-methyl-N-((R)-3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butyl)propane-2-sulfinamide

HRID 2406917Notes

Reaction equation

HRID 2406917 reaction equation
[CH3:1][C:2]([S@:5](/[N:7]=[CH:8]/[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)=[O:6])([CH3:4])[CH3:3].[CH2:25]([Li])[CH:26]([CH3:28])[CH3:27]>O1CCCC1>[CH3:4][C:2]([S@:5]([NH:7][C@@H:8]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:6])([CH3:1])[CH3:3]

Participants

4

Reactant 2

HCID 88540239(NE,R)-2-methyl-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methylidene]propane-2-sulfinamideHCID 178506859HCID 178506859, compound

Product 1

HCID 67981080(R)-2-methyl-N-((R)-3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butyl)propane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A round bottom flask was charged with (R,E)-2-methyl-N-((4′-(trifluoromethyl) biphenyl-4-yl)methylene)propane-2-sulfinamide (25.0 g, 70.7 mmol) and tetrahydrofuran (140 mL) and cooled down to −78° C. To this solution was added isobutyllithium (1.6M in heptane; 50.8 mL) dropwise over 20 minutes. The reaction was allowed to stir at −78° C. for 30 minutes. LC-MS analysis showed complete conversion of the starting material and the formation of two product diastereomers (4.6:1). The reaction was quenched with saturated ammonium chloride and extracted with ethyl acetate twice. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (1-10% ethyl acetate/dichloromethane) allowed isolation of the major isomer (the less polar isomer), (R)-2-methyl-N—((R)-3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butyl)propane-2-sulfinamide (47.5 g, 74.2%) as a colorless gum. 1H NMR (400 MHz, CDCl3, δ): 0.91 (d, 3 H) 0.96 (d, J=6.44 Hz, 3 H) 1.24 (s, 9 H) 1.49-1.59 (m, 1 H) 1.63-1.72 (m, 1 H) 1.84-1.94 (m, 1 H) 3.38 (br. s., 1 H) 4.46 (dd, J=8.19, 6.83 Hz, 1 H) 7.43-7.46 (m, 2 H) 7.56-7.60 (m, 2 H) 7.68-7.70 (m, 4 H). MS (M+1): 412.3.

Workup

  1. customThe reaction was quenched with saturated ammonium chloride
  2. extractionextracted with ethyl acetate twice
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (1-10% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-cdd618a8e88c433cbcf2ab3a8cab45e8
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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