HCID 86612031, compound → HCID 22270706, compound

HRID 133441Notes

Reaction equation

HRID 133441 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH:10]([C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)[C:11](=[N:13][S:14]([CH2:16][CH:17]([CH3:19])[CH3:18])=[O:15])[CH3:12].C[Mg]Br>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH:10]([C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)[CH:11]([NH:13][S:14]([CH2:16][CH:17]([CH3:18])[CH3:19])=[O:15])[CH3:12]

Participants

4

Reactant 2

HCID 86612031HCID 86612031, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 22270706HCID 22270706, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

To a solution of N-[3-(2,4-dichlorophenyl)-2-(4-chlorophenyl)-1-methylpropylidene]-2-methylpropanesulfinamide (Step D, 0.51 g, 1.3 mmol) in 6 mL CH2Cl2 at −60° C. was added methylmagnesium bromide (3 M in ether, 0.90 mL, 2.7 mmol). After stirring at −60° C. for 6 h, the reaction was allowed to warm to room temperature overnight. The resulting mixture was partitioned between saturated aqueous ammonium chloride (50 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2×50 mL). The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated to dryness, and the residue was purified by flash column chromatography on silica gel eluted with 30 to 50% EtOAc in hexane to give the title compound as one pure faster elating enantiomer and a 1:1 mixture of slower co-eluting diastereomers. The addition of the methyl Grignard reagent was apparently stereoselective for one of the sulfinamide diastereomers. Faster eluting isomer: 1H NMR (500 MHz, CD3OD): δ 7.30 (d, 1H), 7.22 (d, 2H), 7.12 (d, 2H), 7.03 (dd, 1H), 6.94 (d, 1H), 3.62 (m, 1H), 3.56 (dd, 1H), 2.97 (dd, 1H), 1.23 (s, 9H), 1.04 (d, 3H). LC-MS: m/e 432 (M+H)+ (4.2 min). Slower eluting isomers (1:1): 1H NMR (500 MHz, CD3OD): δ 7.33/7.30 (d, 1H), 7.21/7.18 (d, 2H), 7.06/7.04 (d, 2H), 6.99/6.97 (dd, 1H), 6.79/6.75 (d, 1H), 3.70-3.55 (m, 1H), 3.07/2.97 (m, 1H), 2.90/2.80 (dd, 1H), 1.32/0.95 (s, 9H), 1.49/1.10 (d, 3H).

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe resulting mixture was partitioned between saturated aqueous ammonium chloride (50 mL) and EtOAc (50 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with EtOAc (2×50 mL)
  5. dry with materialThe combined extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customthe residue was purified by flash column chromatography on silica gel
  9. washeluted with 30 to 50% EtOAc in hexane

Sources & evidence

ORD record
ord-92420efdd602407eb84667d73e5f4e9d
Source dataset
uspto-grants-2008_06
Patent number
US07390835B2

Reaction notes

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