N-bromobutanimide → Tert-butyl 5-chloro-2-oxospiro[indoline-3,3'-pyrrolidine]-1'-carboxylate

HRID 529085Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14][C:5]2=1.BrN1C(=[O:28])CCC1=O>C1COCC1.CC(O)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]3([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[CH2:11]3)[C:6](=[O:28])[NH:7][C:8]2=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of tert-butyl 6-chloro-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (0.500 g, 1.63 mmol) in 1:1:1 THF/AcOH/H2O (45 mL) at about 0° C. was treated with N-Bromosuccinimide (0.319 g, 1.79 mmol) portionwise over about 20 minutes. The resulting mixture was stirred for about 90 minutes at about 0° C. The mixture was then quenched by the addition of saturated Na2CO3 (100 mL) and extracted with DCM. The combined organics were washed with saturated NaHCO3 (2×) and brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by column chromatography (20% EtOAc/Hexane) to yield tert-butyl 5-chloro-2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate (0.530 g, 100%). LCMS (APCI+) m/z 223, 225 [M+H−Boc]+; Rt=3.26 min.

Workup

customThe mixture was then quenched by the addition of saturated Na2CO3 (100 mL)
extractionextracted with DCM
washThe combined organics were washed with saturated NaHCO3 (2×) and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude residue was purified by column chromatography (20% EtOAc/Hexane)

Sources & evidence

ORD record: ord-8ea670f68fa0452e82e1b4c00d109277
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346805B2

Reaction notes

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