Water → HCID 178496587, compound

HRID 731430Notes

Reaction equation

HRID 731430 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])[CH2:4][CH2:3]1.[H-].[Na+].I[CH3:22].O>CN(C=O)C.C(OCC)(=O)C>[CH3:22][O:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([N:8]2[C:9](=[O:18])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:16]2=[O:17])[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178515017HCID 178515017, compound

Product 1

HCID 178496587HCID 178496587, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(trans-4-hydroxy-cyclohexyl)-isoindole-1,3-dione (Glennon et al. J. Med. Chem. 1996, 39, 1, 314-322) (1.0 g, 40.77 mmol) in DMF (4.0 mL) was added NaH (60% in oil, 0.41 g, 10.2 mmol) followed by iodomethane (5.79 g, 40.7 mmol). The reaction mixture was stirred for 16 h before water (15 mL) and ethyl acetate (25 mL) was added and the phases were separated. The organic phase was washed with water (2×10 mL), dried over MgSO4 and the solvent was removed in cacuo. The residue was purified on silica gel (EtOAc-heptane) to give 0.810 g (77%) 2-(trans-4-methoxy-cyclohexyl)-isoindole-1,3-dione. 2-(trans-4-methoxy-cyclohexyl)-isoindole-1,3-dione (0.710 g, 2.74 mmol) in absolute ethanol (10 mL) was added hydrazine hydrate (0.130 g, 4.11 mmol) and the reaction mixture was stirred for 2 h at 50° C. The oilbath was removed and the mixture was stirred for 16 h at room temperature. The volatiles were removed in vacuo and the residue was added NaOH (20 mL, 10 N) and extracted with diethyl ether (3×10 mL). The organic phase was dried with MgSO4 and concentrated in vacuo to give 0.300 g (85%) of 4-trans-methoxy-cyclohexylamine. 4-Trans-methoxy-cyclohexylamine (100 mg, 0.78 mmol) and cyclopentanone (72 mg, 0.85 mmol) in THF-MeOH 2:1 (2 mL) and acetic acid (0.1 mL) was added sodium cyanoborohydride (73 mg, 1.02 mmol) in small portions over 15 min. The reaction mixture was stirred for 16 h before the volatiles were removed in vacuo. The residue was added HCl (1N, 50 mL) and stirred for 16 h at rt. The mixture was added NaOH (10N, 2.5 mL), extracted with diethyl ether (2×10 mL) and dried over MgSO4. The solvent was removed in vacuo to give 134 mg (88%) of cyclopentyl-(4-methoxy-cyclohexyl)-amine.

Workup

  1. additionwas added
  2. customthe phases were separated
  3. washThe organic phase was washed with water (2×10 mL)
  4. dry with materialdried over MgSO4
  5. customthe solvent was removed in cacuo
  6. customThe residue was purified on silica gel (EtOAc-heptane)

Sources & evidence

ORD record
ord-767fe5abbeb944199a7affa4030ddd70
Source dataset
uspto-grants-2009_09
Patent number
US07582769B2

Reaction notes

Loading…