Acetonitrile → 4-{4-[7-Chloro-1-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindol-5-ylmethyl]-piperidin-1-ylmethyl}-benzonitrile

HRID 252074Notes

Reaction equation

HRID 252074 reaction equation
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[CH:5][CH:4]=1)#[N:2].[Cl:11][C:12]1[CH:13]=[C:14]([CH2:34][CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH:15]=[C:16]2[C:20]=1[C:19](=[O:21])[N:18]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)[CH2:17]2.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O>[Cl:11][C:12]1[CH:13]=[C:14]([CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([CH2:7][C:6]3[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[CH2:37][CH2:36]2)[CH:15]=[C:16]2[C:20]=1[C:19](=[O:21])[N:18]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:32])([F:33])[F:31])=[CH:25][CH:24]=1)[CH2:17]2

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 869964-(Bromomethyl)benzonitrileHCID 579492977-Chloro-5-piperidin-4-ylmethyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

Product 1

HCID 160396434-{4-[7-Chloro-1-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindol-5-ylmethyl]-piperidin-1-ylmethyl}-benzonitrileYield 117.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 4-Cyano-benzyl bromide (12 mg, 0.06 mmol), 7-chloro-5-piperidin-4-ylmethyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (30.0 mg, 0.06 mmol) and potassium carbonate (42 mg, 0.3 mmol) was added acetonitrile (3.0 mL). The mixture was allowed to stir at room temperature overnight. Water (2.0 mL) was added and the product was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulfate, filtered and concentrated. Column chromatography provided the title compound as a brown oil (39.0 mg, 99%). 1H NMR (300 MHz, CDCl3): δ 7.60 (d, 2H), 7.27-7.59 (m, 4H), 7.17-7.20 (m, 3H), 7.05 (s, 1H), 4.77 (s, 2H), 4.22 (s, 2H), 3.53 (s, 2H), 2.80-2.84 (m, 2H), 2.58-2.60 (m, 2H), 1.91 (t, 21, 1.56-1.62 (m, 3H), 1.27-1.34 (m, 2H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-61cb04f0b89240c4a2461a6f7590a6ae
Source dataset
uspto-grants-2011_01
Patent number
US07868008B2

Reaction notes

Loading…