Ethyl Acetate → (S)-N-((S)-(3-fluoropyridin-2-yl)(4(trifluoro-methyl)phenyl)methyl)-2-methylpropane-2-sulfinamide

HRID 509311Notes

Reaction equation

HRID 509311 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=1.[F:13][C:14]1[C:15](/[CH:20]=[N:21]/[S@:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])=[N:16][CH:17]=[CH:18][CH:19]=1.CCOC(C)=O>C1COCC1>[F:13][C:14]1[C:15]([C@H:20]([C:3]2[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=2)[NH:21][S@:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 5462224MagnesiumHCID 89310556(NE,S)-N-[(3-fluoro-2-pyridinyl)methylidene]-2-methylpropane-2-sulfinamide

Product 1

HCID 71144543(S)-N-((S)-(3-fluoropyridin-2-yl)(4(trifluoro-methyl)phenyl)methyl)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of magnesium (170 g, 2365 mmol) in THF (1.35 L), was added 4-bromobenzotrifluoride (532 g, 2365 mmol). Stirring was continued for 4 h (caution: slightly exothermic, cooled with a water bath if needed). The solution was cannulated to a stirred solution of (S, E)-N-((3-fluoro-pyridin-2-yl)methylene)-2-methylpropane-2-sulfinamide (270 g, 1182 mmol) in THF (1.3 L) at −78° C. dropwise. Stirring was continued for 1 h. The progress of the reaction was monitored by TLC (50% EtOAc in petroleum ether). After completion of the reaction, the reaction mixture was quenched with saturated aqueous NH4Cl (2.5 L), and the solution was extracted with Et2O (5×500 mL). The organic layers were combined, dried over Na2SO4, concentrated, and purified by column chromatography using silica (100-200 mesh) with 25-30% EtOAc in petroleum ether as eluent to give the title compound as a brown oil. 1H-NMR (400 MHz, CDCl3): δ ppm 8.45 (d, J=3.6 Hz, 1H), 7.73-7.78 (m, 1H), 7.71 (d, J=8.4 Hz, 2H), 7.63 (m, 2H), 7.43-7.48 (m, 1H), 6.23 (d, J=6.8 Hz, 1H), 5.99 (d, J=6.8 Hz, 1H), 1.36 (s, 9H). MS (ESI pos. ion) m/z: 375.1 (M-O and t-Bu).

Workup

  1. temperature(caution: slightly exothermic, cooled with a water bath
  2. stirringStirring
  3. waitwas continued for 1 h
  4. customAfter completion of the reaction
  5. customthe reaction mixture was quenched with saturated aqueous NH4Cl (2.5 L)
  6. extractionthe solution was extracted with Et2O (5×500 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. custompurified by column chromatography

Sources & evidence

ORD record
ord-dad8ace7a9d14530971fc9e9731377a7
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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