Sodium hydride → tert-butyl 2-bromo-3-cyclohexyl-1-(2-methoxy-2-oxoethyl)-1H-indole-6-carboxylate

HRID 1714005Notes

Reaction equation

[H-].[Na+].Br[CH2:4][C:5]([O:7][CH3:8])=[O:6].[Br:9][C:10]1[NH:11][C:12]2[C:17]([C:18]=1[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)=[CH:16][CH:15]=[C:14]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:13]=2>>[Br:9][C:10]1[N:11]([CH2:4][C:5]([O:7][CH3:8])=[O:6])[C:12]2[C:17]([C:18]=1[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)=[CH:16][CH:15]=[C:14]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:13]=2

Participants

Reactant 3

HCID 24758Sodium hydride

HCID 60984Methyl bromoacetate

HCID 59750072tert-Butyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate2×

Product 1

HCID 68511006tert-butyl 2-bromo-3-cyclohexyl-1-(2-methoxy-2-oxoethyl)-1H-indole-6-carboxylateYield 80%

Procedure

NaH (1.4 eq, 60% dispersion in mineral oil) was added to a solution of tert-butyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate in DMF (from Step 5, 0.15 M) and the solution stirred at RT for 30 min. Then methyl bromoacetate (1.4 eq) was added and the mixture stirred at RT for 3 h. The solvent was removed in vacuo and the residue taken up in EtOAc. The organic phase was washed twice with aqueous HCl (0.5 N) and then brine. The organic phase was dried over Na2SO4, filtered and the solvent evaporated in vacuo. The residue was purified by crystallisation (EtOAc/PE) to afford the title compound (80%); MS (ES+) m/z 450 (M+H)+, m/z 452 (M+H)+.

Workup

stirringthe mixture stirred at RT for 3 h
customThe solvent was removed in vacuo
washThe organic phase was washed twice with aqueous HCl (0.5 N)
dry with materialThe organic phase was dried over Na2SO4
filtrationfiltered
customthe solvent evaporated in vacuo
customThe residue was purified by crystallisation (EtOAc/PE)

Sources & evidence

ORD record: ord-98994e008d0144688176e863f998dfb6
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795247B2

Reaction notes

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