HCID 46926628, compound → 4-(3-(4-(Cyclopentyl(hydroxy)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrile

HRID 1503345Notes

Reaction equation

HRID 1503345 reaction equation
[C:1]([CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:27]1([Mg]Cl)[CH2:31][CH2:30][CH2:29][CH2:28]1>C1COCC1>[CH:27]1([C:1]([OH:8])([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=3)[CH2:13][CH2:14]2)[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

4

Reactant 2

HCID 46926628HCID 46926628, compoundHCID 178478989HCID 178478989, compound

Product 1

HCID 469266324-(3-(4-(Cyclopentyl(hydroxy)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrileYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

4-(3-(4-Benzoylpiperidin-1-yl)propoxy)benzonitrile (1.4 g, 4 mmol) was dissolved in dry THF (˜25 mL), heated to 60° C. and a solution of cyclopentylmagnesium chloride (4 mL, 2M) was added and the reaction stirred for 1 h. The reaction was quenched (sat. NH4Cl) and extracted into EtOAc (2×). The organic layers were dried over Na2SO4 and the volatiles removed under reduced pressure. The crude residue was purified on silica gel (0-4% MeOH in CH2Cl2). The combined fractions were further purified by reverse phase chromatography to give 117 mg (7% yield) of analytically pure title compound: 1H NMR (400 MHz, CDCl3) δ 7.54 (2H, d, J=8.8 Hz), 7.37 (2H, d, J=7.6 Hz), 7.31 (2H, t, J=7.6 Hz), 7.22 (1H, t, J=7.2 Hz), 6.89 (2H, d, J=8.8 Hz), 4.02 (2H, t, J=6 Hz), 3.12-3.00 (2H, m), 2.74-2.62 (3H, m), 2.09-1.95 (4H, m), 1.80-1.60 (4H, m), 1.58-1.40 (7H, m), 1.25-1.24 (1H, m), 1.11-1.09 (1H, m); LC-MS (>98%) m/z=419.3 [M+H]; HRMS=419.2701 [M+H], 100%, calculated for C27H35N2O2, 419.2699.

Workup

  1. customThe reaction was quenched (sat. NH4Cl)
  2. extractionextracted into EtOAc (2×)
  3. dry with materialThe organic layers were dried over Na2SO4
  4. customthe volatiles removed under reduced pressure
  5. customThe crude residue was purified on silica gel (0-4% MeOH in CH2Cl2)
  6. customThe combined fractions were further purified by reverse phase chromatography

Sources & evidence

ORD record
ord-870e6b7562794d51af68c9b7e68d2165
Source dataset
uspto-grants-2015_12
Patent number
US09212180B2

Reaction notes

Loading…