tert-Butylsulfinamide, (R)-(+)- → (NE,R)-N-[1-(4-fluoro-3-methoxyphenyl)-2-phenylethylidene]-2-methylpropane-2-sulfinamide

HRID 1712733Notes

Reaction equation

HRID 1712733 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[O:17][CH3:18].[CH3:19][C:20]([S@:23]([NH2:25])=[O:24])([CH3:22])[CH3:21]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5](/[C:8](=[N:25]/[S@@:23]([C:20]([CH3:22])([CH3:21])[CH3:19])=[O:24])/[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[O:17][CH3:18]

Participants

4

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 594584091-(4-Fluoro-3-methoxyphenyl)-2-phenylethanone

Product 1

HCID 59459069(NE,R)-N-[1-(4-fluoro-3-methoxyphenyl)-2-phenylethylidene]-2-methylpropane-2-sulfinamideYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(4-fluoro-3-methoxyphenyl)-2-phenylethanone (13 g, 53 mmol) dissolved in THF (266 mL) was added (R)-2-methylpropane-2-sulfinamide (7.8 g, 64 mmol) at rt, followed by Ti(OEt)4 (17 mL, 80 mmol). The reaction mixture was heated to reflux for 48 h, then allowed to cool to rt. The reaction mixture was concentrated under reduced pressure and the residue was diluted with Et2O. H2O was added and the solid was filtered and washed with Et2O. The filtrate was washed with H2O, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, eluting with 0-100% EtOAc/hexane) to yield (R,E)-N-(1-(4-fluoro-3-methoxyphenyl)-2-phenylethylidene)-2-methylpropane-2-sulfinamide (12 g, 67% yield). LCMS: RT=3.655 min [M+H] 348.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% NH4OAc; 4 mL/min, monitoring at 220 nm); 1H NMR (500 MHz, CDCl3) δ ppm 7.60-7.53 (m, 1H), 7.43-7.36 (m, 1H), 7.29-7.15 (m, 5H), 7.03 (dd, J=11, 8 Hz, 1H), 4.75 (d, J=15 Hz, 1H), 4.54 (d, J=15 Hz, 1H), 3.84 (s, 3H), 1.34 (s, 9H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 48 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was diluted with Et2O
  5. additionH2O was added
  6. filtrationthe solid was filtered
  7. washwashed with Et2O
  8. washThe filtrate was washed with H2O
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash chromatography (SiO2, eluting with 0-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-00f5453101154136815736a2351a1ad8
Source dataset
uspto-grants-2010_09
Patent number
US07790770B2

Reaction notes

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