Water → [(1-{4-[3-(2,2-Dimethylpyrrolidin-1-yl)propoxy]phenyl}-cyclo-hexyl)methyl]amine

HRID 272937Notes

Reaction equation

HRID 272937 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][C:8]1([CH3:31])[CH2:12][CH2:11][CH2:10][N:9]1[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([C:29]#[N:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1.O.[OH-].[Na+]>CCOCC.C(OCC)(=O)C>[NH3:9].[CH3:7][C:8]1([CH3:31])[CH2:12][CH2:11][CH2:10][N:9]1[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([CH2:29][NH2:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 598374311-{4-[3-(2,2-Dimethylpyrrolidin-1-yl)propoxy]phenyl}cyclohexanecarbonitrile

Product 2

HCID 222AmmoniaHCID 59837363[(1-{4-[3-(2,2-Dimethylpyrrolidin-1-yl)propoxy]phenyl}-cyclo-hexyl)methyl]amineYield 73.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
7.5 °C

Procedure

To a stirred suspension of LiAlH4 (1.0M in diethyl ether, 0.4 ml, 0.40 mmol) at 0° C. under an atmosphere of nitrogen was added 1-{4-[3-(2,2-dimethylpyrrolidin-1-yl)propoxy]phenyl}cyclohexanecarbonitrile (27 mg, 0.079 mmol) in Et2O (15 mL) over 15 minutes maintaining the temperature at 5 to 10° C. The reaction mixture was allowed to warm up to ambient temperature for 20 minutes then refluxed for 30 minutes until complete. The reaction mixture was cooled to 0° C., water (0.5 mL) was added followed by NaOH (2.0M, 1.5 mL) and water (0.5 mL). Ethyl acetate (5 mL) was added and the mixture filtered through a short pad of celite, eluting with ethyl acetate (2×15 mL) and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to give the title compound as a clear oil (10 mg, 37%). 1H NMR (400 MHz, CDCl3) δ 7.22 (d, 2H), 6.84 (d, 2H), 4.02 (t, 2H), 2.86-2.76 (m, 2H), 2.66 (s, 2H), 2.58-2.50 (m, 2H), 2.16-2.06 (m, 2H), 2.00-2.90 (m, 2H), 1.84-1.72 (m, 2H), 1.70-1.64 (m, 2H), 1.56-1.46 (m, 4H), 1.40-1.32 (m, 4H), 1.02 (s, 6H). HRMS (ESI+) 345.2901 (M+H)+.

Workup

  1. temperatureto warm up to ambient temperature for 20 minutes
  2. temperaturethen refluxed for 30 minutes until complete
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. filtrationthe mixture filtered through a short pad of celite
  5. washeluting with ethyl acetate (2×15 mL)
  6. concentrationconcentrated in vacuo
  7. customThe compound was purified by column chromatography on Biotage® silica gel
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-2cce50cdae2042c7aff55028b0f02061
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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