Sodium Hydroxide → cis-Rac-4-phenyl-8-(2-p-tolyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 347308Notes

Reaction equation

HRID 347308 reaction equation
[C:1]1([CH3:14])[CH:6]=[CH:5][C:4]([CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][C:8]2=[O:13])=[CH:3][CH:2]=1.[C:15]1([CH:21]2[C:25]3([CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:24](=[O:31])[NH:23][CH2:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH4+:23].[OH-:13].[C:15]1([CH:21]2[C:25]3([CH2:26][CH2:27][N:28]([C@@H:8]4[CH2:9][CH2:10][CH2:11][CH2:12][C@@H:7]4[C:4]4[CH:5]=[CH:6][C:1]([CH3:14])=[CH:2][CH:3]=4)[CH2:29][CH2:30]3)[C:24](=[O:31])[NH:23][CH2:22]2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 30406522-(4-Methylphenyl)cyclohexanoneHCID 127097244-Phenyl-2,8-diazaspiro[4.5]decan-1-one

Product 2

HCID 14923Ammonium HydroxideYield 25%HCID 131726233cis-Rac-4-phenyl-8-(2-p-tolyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 62.1%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of rac-2-p-tolyl-cyclohexanone (410 mg, 2 mmol), rac-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one (502 mg, 2 mmol) and titanium(IV) isopropoxide (810 uL, 3 mmol) were stirred at rt for 3 h. The mixture was then diluted with THF (5 mL) and then a solution of polymethylhydroxysiloxane (261 mg, 4 mmol) in THF (5 mL) was added and the resulting solution stirred at rt overnight. To this solution Na(CN)BH3 (245 mg) was added and the resulting mixture stirred at rt for 3 h. Then NaOH (3M, 10 mL) was added and the mixture stirred for 1 h. The resulting precipitate was then filtered off over celite and the filtrate was washed with brine, dried and evaporated to leave a light yellow foam. Purification by chromatography on silica gel eluting with DCM:MeOH:NH4OH (25%) (98:2:0.1 to 95:4.5:0.5) afforded the title compound (250 mg, 29%) which was obtained as a white solid. MS: m/e=403.6 (M+H).

Workup

  1. stirringthe resulting solution stirred at rt overnight
  2. stirringthe resulting mixture stirred at rt for 3 h
  3. stirringthe mixture stirred for 1 h
  4. filtrationThe resulting precipitate was then filtered off over celite
  5. washthe filtrate was washed with brine
  6. customdried
  7. customevaporated
  8. customto leave a light yellow foam
  9. customPurification by chromatography on silica gel eluting with DCM

Sources & evidence

ORD record
ord-dbd7eb9c1ba54f139ec1c09938d8b67b
Source dataset
uspto-grants-2007_02
Patent number
US07173133B2

Reaction notes

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