tert-Butylsulfinamide, (R)-(+)- → (NZ,R)-N-[1-(1-benzylpiperidin-4-yl)pent-4-enylidene]-2-methylpropane-2-sulfinamide

HRID 579583Notes

Reaction equation

HRID 579583 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=O)[CH2:15][CH2:16][CH:17]=[CH2:18])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][C:21]([S@:24]([NH2:26])=[O:25])([CH3:23])[CH3:22]>C1COCC1.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11](/[C:14](=[N:26]\[S@@:24]([C:21]([CH3:23])([CH3:22])[CH3:20])=[O:25])/[CH2:15][CH2:16][CH:17]=[CH2:18])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-2×HCID 668336681-(1-Benzylpiperidin-4-yl)pent-4-en-1-one

Product 1

HCID 87173115(NZ,R)-N-[1-(1-benzylpiperidin-4-yl)pent-4-enylidene]-2-methylpropane-2-sulfinamideYield 42.2%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1-(1-benzylpiperidin-4-yl)pent-4-en-1-one (6.11 g, 21.3 mmol) and (R)-2-methylpropane-2-sulfinamide (3.62 g, 27.6 mmol) in THF (71 mL, 0.3 M) was treated with titanium (IV) ethoxide (12.6 g, 55.3 mmol) and heated to 70° C. overnight. Because the reaction was incomplete, additional portions of (R)-2-methylpropane-2-sulfinamide (1.81 g, 13.8 mmol) and titanium (IV) ethoxide (6.3 g, 27.7 mmol) were added and the mixture was heated to 75° C. for 6 more hours. The reaction was quenched by pouring it slowly into rapidly stirred saturated aqueous sodium chloride (100 mL) and filtering through Celite. The Celite pad was washed with ethyl acetate (3×) and the combined organics were washed with saturated aqueous sodium chloride, dried over MgSO4, and concentrated in vacuo. The residue was chromatographed on silica gel (60% ethyl acetate in heptane) to afford the desired product (3.24 g, 42%). Rf 0.44 (EtOAc). 1H NMR (CDCl3, 300 MHz) δ 7.34-7.19 (m, 5H), 5.88-5.75 (m, 1H), 5.09-4.94 (m, 2H), 3.50 (d, J=5.5 Hz, 2H), 2.97-2.83 (m, 2H), 2.74-2.70 (m, 1H), 2.55-2.23 (m, 4H), 2.00 (t, J=8.8 Hz, 2H), 1.77-1.63 (m, 4H), 1.23 (s, 9H). ESI MS found for C21H32N2OS m/z [361.4 (M+1)].

Workup

  1. temperaturethe mixture was heated to 75° C. for 6 more hours
  2. customThe reaction was quenched
  3. additionby pouring it slowly into rapidly stirred saturated aqueous sodium chloride (100 mL)
  4. filtrationfiltering through Celite
  5. washThe Celite pad was washed with ethyl acetate (3×)
  6. washthe combined organics were washed with saturated aqueous sodium chloride
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was chromatographed on silica gel (60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-df2ed6e757a54405898879f97e76c754
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…