Ethyl Acetate → tert-Butyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1713949Notes

Reaction equation

HRID 1713949 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[C:15]2[C:11]([C:12]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)=[CH:13][NH:14]2)=[CH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:30])C(=O)C1.S([O-])([O-])(=O)=S.[Na+].[Na+].CCOC(C)=O>C(Cl)(Cl)(Cl)Cl>[Br:30][C:13]1[NH:14][C:15]2[C:11]([C:12]=1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)=[CH:10][CH:9]=[C:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:16]=2

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24477Sodium ThiosulfateHCID 67184N-bromobutanimideHCID 68433774tert-butyl 3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 59750072tert-Butyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

To a solution (0.14 M) of tert-butyl-3-cyclohexyl-1H-indole-6-carboxylate in CCl4 was added NBS (1.1 eq.) portionwise over a period of 1 h at RT. The resulting mixture was stirred 2 h at RT, then a saturated aqueous solution of sodium thiosulfate was added and the reaction mixture vigorously stirred for 1 h. EtOAc was then added and the organic layer was separated and washed with a saturated aqueous solution of sodium thiosulfate (3×) then dried over Na2SO4 and evaporated. The residue was purified by silica gel chromatography (Flashmaster Personal, petroleum ether:EtOAc, 20:1) to give the title compound (68%) as a solid. 1H NMR (300 MHz, DMSO-d6, 300 K) δ 1.33-1.39 (m, 3H), 1.54 (s, 9H), 1.65-1.99 (m, 7H), 2.73-2.81 (m, 1H), 7.52 (d, J 7.6, 1H), 7.70 (d, J 77.6, 1H), 7.83 (s, 1H), 11.92 (br s, 1H); MS (ES+) m/z 379 (M+H)+.

Workup

  1. stirringthe reaction mixture vigorously stirred for 1 h
  2. customthe organic layer was separated
  3. washwashed with a saturated aqueous solution of sodium thiosulfate (3×)
  4. dry with materialthen dried over Na2SO4
  5. customevaporated
  6. customThe residue was purified by silica gel chromatography (Flashmaster Personal, petroleum ether:EtOAc, 20:1)

Sources & evidence

ORD record
ord-f168018585304e1dbe29143eb1c56bd0
Source dataset
uspto-grants-2010_09
Patent number
US07795250B2

Reaction notes

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