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

HRID 1713948Notes

Reaction equation

HRID 1713948 reaction equation
[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C(NC(=NC(C)C)O[C:25]([CH3:28])([CH3:27])[CH3:26])(C)C.NC(=N)O>C(Cl)Cl>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 110417822-tert-Butyl-1,3-diisopropylisoureaHCID 111840773-(Cyclohex-1-en-1-yl)-1H-indole-6-carboxylic acidHCID 178513210HCID 178513210, compound

Product 1

HCID 68433774tert-butyl 3-cyclohexyl-1H-indole-6-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-cyclohexenyl-1H-indole-6-carboxylic acid (1 eq., prepared as described in Example 1, Step 1) in dry DCM (0.19 M) was treated with tert-butyl N,N′-diisopropylimidocarbamate (2 eq.). The resulting clear solution was heated at reflux for 36 h. Addition of a further equivalent of isourea was required after 16 h to drive the reaction to completion. After cooling down the solvent was evaporated giving a residue that was purified by silica gel chromatography (Flashmaster Personal, PE:EtOAc, 30:1) affording tert-butyl 3-cyclohexyl-1H-indole-6-carboxylate (75%) 1H NMR (300 MHz, DMSO-d6, 300 K) δ 1.22-1.53 (m, 5H), 1.54 (s, 9H), 1.70-1.86 (m, 3H), 1.95-1.98 (m, 2H), 2.69-2.86 (m, 1H), 7.29 (s, 1H), 7.49-7.57 (m, 2H), 7.93 (s, 1H), 11.09 (s, 1H); MS (ES+) m/z 300 (M+H)+.

Workup

  1. temperatureThe resulting clear solution was heated
  2. temperatureat reflux for 36 h
  3. customthe reaction to completion
  4. temperatureAfter cooling down the solvent
  5. customwas evaporated
  6. customgiving a residue that
  7. customwas purified by silica gel chromatography (Flashmaster Personal, PE:EtOAc, 30:1)

Sources & evidence

ORD record
ord-e6edab92a45a4e82bcdf430716e17c28
Source dataset
uspto-grants-2010_09
Patent number
US07795250B2

Reaction notes

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