HCID 118045345, compound → HCID 118045947, compound

HRID 595985Notes

Reaction equation

HRID 595985 reaction equation
C[Zn]C.[CH:4]([Mg]Br)=[CH2:5].[F:8][C:9]1[CH:10]=[C:11]([CH:20]=[C:21]([CH2:23][F:24])[CH:22]=1)/[CH:12]=[N:13]/[S@@:14]([C:16]([CH3:19])([CH3:18])[CH3:17])=[O:15]>C1COCC1>[F:8][C:9]1[CH:10]=[C:11]([C@H:12]([NH:13][S@@:14]([C:16]([CH3:19])([CH3:18])[CH3:17])=[O:15])[CH:4]=[CH2:5])[CH:20]=[C:21]([CH2:23][F:24])[CH:22]=1

Participants

5

Reactant 3

HCID 118045345HCID 118045345, compoundHCID 178418507HCID 178418507, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 118045947HCID 118045947, compoundYield 66.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Dimethyl Zinc (2M in Toluene) (0.434 mL, 0.868 mmol) and vinylmagnesium bromide (1M in THF) (4.51 mL, 4.51 mmol) was mixed at room temperature for 20 min under argon before cooling down to −78° C., then (R,E)-N-(3-fluoro-5-(fluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (0.900 g, 3.47 mmol) in dry THF (11.57 mL) as added dropwise, maintain the internal temperature between −74° C. to −72° C., after addition the reaction mixture was stirred at −78° C. for 1 h, the reaction was quenched by sat.NH4Cl, THF was removed in vacuo, then extracted by EtOAc. The organic was washed by water and brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (0-30% EtOAc/heptaneatane) to yield product 660 mg, LCMS (m/z): 288.0 (MH+), 0.83 min. 1H NMR (400 MHz, CDCl3) δ ppm 7.14 (s, 1H), 7.03 (d, J=9.0 Hz, 1H), 7.07 (d, J=9.4 Hz, 1H), 5.90 (ddd, J=7.4, 10.1, 17.3 Hz, 1H), 5.45-5.35 (m, 2H), 5.35-5.25 (m, 2H), 5.01-4.94 (m, 1H), 3.45 (br. s., 1H), 1.30-1.22 (m, 9H)

Workup

  1. temperaturemaintain the internal temperature between −74° C. to −72° C.
  2. additionafter addition the reaction mixture
  3. customthe reaction was quenched
  4. customNH4Cl, THF was removed in vacuo
  5. extractionextracted by EtOAc
  6. washThe organic was washed by water and brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography (0-30% EtOAc/heptaneatane)

Sources & evidence

ORD record
ord-6039e3eea4ec4fa6bb090750f19eb53b
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

Loading…