2-tert-Butyl-1,3-diisopropylisourea → tert-butyl 3-cyclohexyl-1H-indole-6-carboxylate

HRID 1714003Notes

Reaction equation

HRID 1714003 reaction equation
C(NC(=NC(C)C)O[C:7]([CH3:10])([CH3:9])[CH3:8])(C)C.[CH:15]1([C:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30]([OH:32])=[O:31])=[CH:27][CH:28]=3)[NH:23][CH:22]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>C(Cl)Cl>[CH:15]1([C:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30]([O:32][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:31])=[CH:27][CH:28]=3)[NH:23][CH:22]=2)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 110417822-tert-Butyl-1,3-diisopropylisourea2×HCID 112419893-cyclohexyl-1H-indole-6-carboxylic Acid

Product 1

HCID 68433774tert-butyl 3-cyclohexyl-1H-indole-6-carboxylateYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2 eq of tert-butyl N,N′-diisopropylimidocarbamate (prepared according to literature precedent: Synthesis 1979, 561) were added to a solution of 3-cyclohexyl-1H-indole-6-carboxylic acid (prepared as described in published International patent application WO2004087714) in CH2Cl2 (0.4 M) and the mixture heated at reflux under N2 for 16 h. A further 2.5 eq of tert-butyl N,N′-diisopropylimidocarbamate were then added portionwise over 3 h, with heating being resumed after each addition. The reaction mixture was then filtered whilst hot through a pad of CELITE and the filtrate concentrated in vacuo. The residue was purified by flash chromatography (5% EtOAc/PE) to afford the title compound (58%); MS (ES−) m/z 298 (M−H)−.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux under N2 for 16 h
  3. temperaturewith heating being
  4. additionafter each addition
  5. filtrationThe reaction mixture was then filtered whilst hot through a pad of CELITE
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe residue was purified by flash chromatography (5% EtOAc/PE)

Sources & evidence

ORD record
ord-d63f171e3edc404ea7cfadba9b15aded
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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