Dimethylformamide → (1R,2R)-methyl-3-((-5'-fluoro-2-(4-iodophenyl)-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate

HRID 1805310Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C@:5]12[CH2:13][C@:12]1([C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][CH:18]=1)[CH:14]([CH3:16])[CH3:15].[C:24]([O-:27])([O-])=O.[Cs+].[Cs+].CN([CH:33]=[O:34])C>>[CH3:24][O:27][C:33](=[O:34])[C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([CH2:5][N:7]2[C:8]3[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)[C@:5]3([CH2:13][C@:12]3([C:17]3[CH:18]=[CH:19][C:20]([I:23])=[CH:21][CH:22]=3)[CH:14]([CH3:16])[CH3:15])[C:6]2=[O:11])[CH:3]=1

Participants

Reactant 3

HCID 6228Dimethylformamide

HCID 10796Cesium carbonate

HCID 58305290(1R,2R)-5'-fluoro-2-(4-iodophenyl)-2-isopropylspiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58305329(1R,2R)-methyl-3-((-5'-fluoro-2-(4-iodophenyl)-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoateYield 92%

Procedure

(1S,2S) and (1R,2R)-5′-fluoro-2-(4-iodophenyl)-2-isopropylspiro[cyclopropane-1,3′-indolin]-2′-one (0.88 g, 2.1 mmol), methyl-(3-bromomethyl)-benzoate (725 mg, 3.15 mmol) and Cs2CO3 (1.37 g, 4.2 mmol) were mixed in anhydrous DMF and stirred at room temperature for 14 hours. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (gradient elution, 15-25% ethyl acetate in petroleum ether) to give the title product as white solid (1.10 g, 92%). LC/MS m/e calcd. for C28H25FINO: 569, observed (M+H)+: 570.1

Workup

customThe solvent was removed under reduced pressure
customThe residue was purified by flash column chromatography (gradient elution, 15-25% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-e5388b9ad27c4ff6bcec15cabcfe3d31
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354443B2

Reaction notes

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