Tetrahydrofuran → (S)-N-(4-(3,4-dichlorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamide

HRID 1848383Notes

Reaction equation

HRID 1848383 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10]/[CH:11]=[N:12]/[S@:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:19][Mg]Br.C1COCC1>C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH:11]([NH:12][S@:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])[CH3:19])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 89477639(NE,S)-N-[3-(3,4-dichlorophenyl)propylidene]-2-methylpropane-2-sulfinamideHCID 178418573HCID 178418573, compound

Product 1

HCID 86728181(S)-N-(4-(3,4-dichlorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamideYield 67%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Intermediate 16B (4.00 g, 13.1 mmol) in DCM (50 mL) was added slowly a solution of methylmagnesium bromide in toluene and THF (13.99 mL, 1.400 M, 19.59 mmol) and the reaction mixture was heated to reflux for 2.5 h. The reaction mixture was allowed to cool to rt and, diluted with DCM, washed with saturated NH4Cl, and the organic portion dried over MgSO4, filtered and concentrated. The residue was purified by ISCO chromatography (EtOAc/Hexanes 0-50% over 30 min, column 330 g, flow rate 100 mL/min) to give Intermediate 16C (2.80 g, 8.69 mmol, 67.0% yield) as a white solid. HPLC/MS (Method D) RT=1.12 min, [M+1]+ 322.1; Chiral HPLC (Method L) RT=4.55 min, PA=100%.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 2.5 h
  3. washwashed with saturated NH4Cl
  4. dry with materialthe organic portion dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by ISCO chromatography (EtOAc/Hexanes 0-50% over 30 min, column 330 g, flow rate 100 mL/min)

Sources & evidence

ORD record
ord-24c493bb021d4840a648c3cdaade065f
Source dataset
uspto-grants-2015_02
Patent number
US08952180B2

Reaction notes

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