Water → 4-Hydroxy-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]cyclo-hexanecarbonitrile

HRID 272929Notes

Reaction equation

HRID 272929 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[O:7]=[C:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:18][CH:17]=2)([C:14]#[N:15])[CH2:10][CH2:9]1.O.[OH-].[Na+]>C(OCC)C>[OH:7][CH:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:18][CH:17]=2)([C:14]#[N:15])[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 230916474-Oxo-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarbonitrile

Product 1

HCID 230916464-Hydroxy-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]cyclo-hexanecarbonitrileYield 41.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred suspension of LiAlH4 (0.070 g, 1.85 mmol, 5 eq) in diethyl ether (1.9 mL) was added dropwise at 0° C. a solution of 4-oxo-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarbonitrile (0.12 g, 0.37 mmol) in diethyl ether (5.5 mL). The reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was cooled to 0° C. and, successively, a solution of water, sodium hydroxide (15% w/v, 0.08 mL) and water again were carefully dropped. After being stirred for 15 min at room temperature, the mixture was filtered over diatomaceous earth and concentrated. The residue was purified by flash chromatography (10 g silica gel, DCM/MeOH (10% NH3) to provide 0.050 g of title compound. 1H NMR (400 MHz, DMSO-D6) δ10.6 (bs, 1H), 7.42 (d, 2H), 7 (d, 2H), 4.1-3.95 (m, 2H), 3.6-3.2 (m, 5H), 3.03-2.87 (m, 2H), 2.15-1.8 (m, 10H), 1.65-1.5 (m, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringAfter being stirred for 15 min at room temperature
  3. filtrationthe mixture was filtered over diatomaceous earth
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (10 g silica gel, DCM/MeOH (10% NH3)

Sources & evidence

ORD record
ord-9315f45ecdba437db7f75f3b40ba9515
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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