Sodium hydride → 2-Bromo-1-tert-butoxycarbonylmethyl-3-cyclohexyl-1H-indole-6-carboxylic acid methyl ester

HRID 1713928Notes

Reaction equation

[Br:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[H-].[Na+].[C:23]([O:27][C:28](=[O:31])[CH2:29]Br)([CH3:26])([CH3:25])[CH3:24]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[N:3]([CH2:29][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:31])[C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2

Participants

Conditions

Temperature: 25 °C

Procedure

A solution (0.1 M) of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate in DMF was treated at 0° C. with NaH (1.3 eq.) and then stirred at 25° C. for 1 h. The solution was treated with tert-butylbromoacetate (1.2 eq.) and stirred 25° C. for 12 h. The mixture was diluted with EtOAc and washed sequentially with HCl (1 N) and brine. The dried organic phase was concentrated and the residue purified by flash chromatography on silica gel (5:95 EtOAc/PE) to afford the title compound (83%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6, 300 K) δ 1.31-1.53 (m, 3H), 1.42 (s, 9H), 1.64-2.02 (m, 7H), 2.77-2.96 (m, 1H), 3.88 (s, 3H), 5.12 (s, 2H), 7.68 (dd, J 8.4, 1.2, 1H), 7.84 (d, J 8.4, 1H), 8.16 (d, J 1.2, 1H); MS (ES+) m/z 452 (M+H)+.

Workup

stirringstirred 25° C. for 12 h
washwashed sequentially with HCl (1 N) and brine
concentrationThe dried organic phase was concentrated
customthe residue purified by flash chromatography on silica gel (5:95 EtOAc/PE)

Sources & evidence

ORD record: ord-1bb483511ed84cd7a6bb220732204149
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795250B2

Reaction notes

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