Acetone cardice → (S)-N-((S)-1-(1-(4-chlorophenyl)-1H-imidazol-4-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 57431Notes

Reaction equation

HRID 57431 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11](/[CH:13]=[N:14]/[S@:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])[N:10]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:21]C(C)=O.C(=O)=O.C[Mg+].[Br-].CCOC(C)=O.CO>C(Cl)Cl.C(OCC)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C@@H:13]([NH:14][S@:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])[CH3:21])[N:10]=[CH:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 18522661Acetone cardiceHCID 21584119Ethylacetate methanolHCID 90415295(NE,S)-N-[[1-(4-chlorophenyl)imidazol-4-yl]methylidene]-2-methylpropane-2-sulfinamideHCID 178418689HCID 178418689, compound

Product 1

HCID 90416206(S)-N-((S)-1-(1-(4-chlorophenyl)-1H-imidazol-4-yl)ethyl)-2-methylpropane-2-sulfinamideYield 62%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of (S,E)-N-((1-(4-chlorophenyl)-1H-imidazol-4-yl)methylene)-2-methylpropane-2-sulfinamide (1.69 g, 5.45 mmol) in DCM (27 mL), cooled to −40° C. (acetone/dry ice) under N2, was added 3M MeMgBr (7.27 ml, 21.8 mmol) in diethyl ether. Reaction mixture allowed to stir for 1 hr at −40° C. Reaction mixture was quenched with the slow addition of a saturated solution of NH4Cl and diluted with EtOAc. Phases partitioned, aqueous phase extracted with EtOAc and the organic layers combined washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/MeOH:EtOAc 0 to 5%) provided (S)—N—((S)-1-(1-(4-chlorophenyl)-1H-imidazol-4-yl)ethyl)-2-methylpropane-2-sulfinamide (1.11 g, 3.41 mmol, 62% yield). 1H NMR (400 MHz, CDCL3) δ 1.25 (s, 9H) 1.58 (d, J=6.65 Hz, 3H) 3.80 (d, J=5.48 Hz, 1H) 4.59 (quin, J=6.36 Hz, 1H) 7.26 (s, 1H) 7.33 (d, J=8.61 Hz, 2H) 7.41-7.47 (m, 2H) 7.76 (d, J=1.17 Hz, 1H). LCMS m/z 326.1 (M+H)+, Rt 0.59 min.

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. customwas quenched with the slow addition of a saturated solution of NH4Cl
  4. additiondiluted with EtOAc
  5. customPhases partitioned
  6. extractionaqueous phase extracted with EtOAc
  7. washthe organic layers combined washed with water, brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-61bbbbcd52614fdea020a9965ddeeb15
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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