Dimethyl Sulfoxide → (1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1805304Notes

Reaction equation

HRID 1805304 reaction equation
[H-].[Na+].[I-].[CH3:4][S+:5]([CH3:8])([CH3:7])=[O:6].[CH3:9]S(C)=O.[Cl:13][C:14]1[CH:30]=[CH:29][C:17](/[CH:18]=[C:19]2\[C:20](=[O:28])[NH:21][C:22]3[C:27]\2=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=1>C1COCC1>[CH3:7][S:5]([CH3:8])(=[O:6])=[CH2:4].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C@@H:18]2[C@:19]3([C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][C:20]3=[O:28])[CH2:9]2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 53982193-(4-Chlorobenzylidene)indolin-2-one

Product 2

HCID 6396768Dimethylsulfoxonium methylideHCID 58305285(1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of dimethylsulfoxoniummethylide was prepared as under argon from a 60% NaH mineral oil dispersion (88 mg, 2.2 mmol), trimethylsulfoxoniumiodide (484 mg, 2.2 mmol), and DMSO (10 mL). After 20 min, a solution of (Z)-3-(4-chloro-benzylidene)-1,3-dihydro-indol-2-one (510 mg, 2 mmol) in THF (5 mL) was added dropwise over 20 min. After stirring for 1 hour at room temperature and another 1 hour at 50° C., the solution was poured into ice-cold water (20 mL) and extracted with ether (3×20 mL). The combined ethereal extracts were washed with brine, dried and evaporated to an oil, which was purified by flash column chromatography (gradient elution, 15-25% ethyl acetate in petroleum ether to give the title compound as white solid (333 mg, 62%). LC/MS m/e calcd. for C16H12ClNO 269, observed (M+H)+:270.5. 1H NMR (400 MHz, DMSO-d6) δppm 1.95 (dd, J=8.97, 4.67 Hz, 1 H) 2.21 (dd, J=7.83, 4.80 Hz, 1 H) 3.04 (t, J=8.46 Hz, 1 H) 6.08 (d, J=7.58 Hz, 1 H) 6.59-6.71 (m, 1 H) 6.87 (d, J=7.58 Hz, 1 H) 7.01-7.10 (m, 1 H) 7.27-7.33 (m, 2 H) 7.33-7.40 (m, 2 H) 10.59 (s, 1 H).

Workup

  1. extractionextracted with ether (3×20 mL)
  2. washThe combined ethereal extracts were washed with brine
  3. customdried
  4. customevaporated to an oil, which
  5. customwas purified by flash column chromatography (
  6. washgradient elution, 15-25% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-5cdff64a48834e1db025afc71e33e12a
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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