N,N,N',N'-Tetramethylethylenediamine → 6'-Bromospiro[cyclopentane-1,3'-indolin]-2'-one

HRID 1619099

Reaction equation

[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[Br:6][C:7]1[CH:15]=[C:14]2[C:10]([CH2:11][C:12](=[O:16])[NH:13]2)=[CH:9][CH:8]=1.CN(C)CCN(C)C.ICCCCI.[Cl-].[NH4+]>O1CCCC1>[Br:6][C:7]1[CH:15]=[C:14]2[C:10]([C:11]3([CH2:4][CH2:3][CH2:2][CH2:1]3)[C:12](=[O:16])[NH:13]2)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: -20 °C

Procedure

n-Butyl lithium (2.5 M in hexanes, 3.8 mL, 9.5 mmol) was added dropwise over 30 minutes to a stirred suspension of 6-bromoindolin-2-one (preparation 1, 1.00 g, 4.7 mmol) and N,N,N′,N′-tetramethylethylenediamine (1.42 mL, 9.4 mmol) in tetrahydrofuran (20 mL) at −78° C. The mixture was stirred for 1 hour, then 1,4-diiodobutane (3.11 mL, 23.6 mmol) was added dropwise over 5 minutes. The mixture was warmed to −20° C. over a 1 hour period, was stirred for a further hour at this temperature and was then warmed to room temperature. After 3 hours stirring at room temperature, saturated aqueous ammonium chloride solution was added to the reaction and the mixture was extracted with ethyl acetate. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. Purification of the residue by flash chromatography (10:1 hexanes/ethyl acetate) gave the title compound (0.57 g, 45%) as a pale pink solid.

Workup

stirringwas stirred for a further hour at this temperature
temperaturewas then warmed to room temperature
stirringAfter 3 hours stirring at room temperature
extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with water, brine
dry with materialdried (MgSO4)
customevaporated
customPurification of the residue by flash chromatography (10:1 hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-f6b086492ca44bd5bd1fbd33eea48b0c
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772288B2

Linked notes

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