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

HRID 1805325Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[NH:12][C:11]3=[O:19])[CH2:9]2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:30][O:31][CH:32]([O:35][CH3:36])[CH2:33]Br.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:33][CH:32]([O:35][CH3:36])[O:31][CH3:30])[C:11]3=[O:19])[CH2:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (1R,2S) and (1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one (135 mg, 1 mmol) in DMF (1 mL) was added KHMDS (0.5 M in THF, 1.1 mL) was dropwise at room temperature. The mixture was stirred for half an hour before adding bromoacetaldehyde dimethyl acetal (95 mg, 0.55 mmol). The mixture was warmed to 50° C. and stirred at that temperature for 2 hours. The mixture was poured into water, extracted with ethyl acetate (3×15 mL), dried and concentrated under reduced pressure. Purification by flash column chromatography on silica gel, eluting with hexanes-EtOAc (6:1 and then 4:1) gave the desire product as colorless oil (268 mg, 75%). LC/MS m/e calcd. for C20H20ClNO3: 3570, observed (M+H)+: 358.7.

Workup

customwas dropwise at room temperature
stirringstirred at that temperature for 2 hours
extractionextracted with ethyl acetate (3×15 mL)
customdried
concentrationconcentrated under reduced pressure
customPurification by flash column chromatography on silica gel
washeluting with hexanes-EtOAc (6:1

Sources & evidence

ORD record: ord-af6981a13fa142a5beb5a96a19512926
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354443B2

Reaction notes

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