Potassium Hydroxide → tert-butyl 3-cyclohexyl-2-phenyl-1H-indole-6-carboxylate

HRID 1713924Notes

Reaction equation

HRID 1713924 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12](C(OC)=O)=[CH:13][CH:14]=3)[NH:9][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[K+].C(N[C:32](=NC(C)C)[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])(C)C.C(=N)([O-:44])N>C1COCC1.O>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:32]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:44])=[CH:13][CH:14]=3)[NH:9][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 110417822-tert-Butyl-1,3-diisopropylisoureaHCID 11416343Methyl 3-cyclohexyl-2-phenyl-1H-indole-6-carboxylateHCID 22499839Imidocarbamate

Product 1

HCID 68436344tert-butyl 3-cyclohexyl-2-phenyl-1H-indole-6-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 3-cyclohexyl-2-phenyl-1H-indole-6-carboxylate (from Step 4) was dissolved in THF (0.2 M) and treated with aqueous KOH (2 eq., 1 M solution). The resulting mixture was heated to 80° C. for 4 h and then cooled to RT. The mixture was diluted with water and extracted with EtOAc (2×). The aqueous phase was acidified to pH 2 using hydrochloric acid (1 M) and then extracted with DCM and EtOAc. Drying over Na2SO4 and evaporation left a grey powder, which was dissolved in DCM (0.3 M). tert-Butyl N,N′-diisopropylimidocarbamate (2 eq.) was added in one portion, and the mixture stirred overnight. Another 2 eq. of the imidocarbamate were added at this point, and the heterogeneous mixture was stirred for another 24 h. Evaporation gave a white powder, which was loaded onto a column containing silica gel. Elution with PE/EtOAc (10:1) gave the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3, 300K) δ 1.30-1.47 (m, 3H), 1.62 (s, 9H), 1.74-1.96 (m, 5H), 1.99-2.16 (m, 2H), 2.95 (t, J 12.4, 1H), 7.40-7.48 (m, 1H), 7.49-7.61 (m, 4H), 7.74 (d, J 8.6, 1H), 7.84 (d, J 8.6, 1H), 8.05 (s, 1H), 8.11 (bs, 1H). MS (ES+) m/z 376 (M+H)+.

Workup

  1. temperaturecooled to RT
  2. extractionextracted with EtOAc (2×)
  3. extractionextracted with DCM and EtOAc
  4. dry with materialDrying over Na2SO4 and evaporation
  5. waitleft a grey powder, which
  6. dissolutionwas dissolved in DCM (0.3 M)
  7. stirringthe heterogeneous mixture was stirred for another 24 h
  8. customEvaporation
  9. customgave a white powder, which
  10. additioncontaining silica gel
  11. washElution with PE/EtOAc (10:1)

Sources & evidence

ORD record
ord-91564f59c75c4101a8f5efc9b4a18397
Source dataset
uspto-grants-2010_09
Patent number
US07795250B2

Reaction notes

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