Sodium hydride → 6-{(RS)-1-[(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-propoxy}-nicotinonitrile

HRID 906929Notes

Reaction equation

HRID 906929 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([CH:21]([OH:24])[CH2:22][CH3:23])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:26]1[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][N:27]=1.[H-].[Na+]>CN(C=O)C>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([CH:21]([O:24][C:26]2[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][N:27]=2)[CH2:22][CH3:23])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 67131651(RS)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-propan-1-ol

Product 1

HCID 671313936-{(RS)-1-[(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-propoxy}-nicotinonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (RS)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-propan-1-ol (described herein above) (21.0 mg, 0.0576 mmol) and 6-chloro-nicotinonitrile (9.6 mg, 0.069 mmol) in 1 mL of DMF was added sodium hydride (60%, 10 mg, 0.25 mmol) at room temperature. The mixture was stirred over night and quenched by an addition of aq. ammonium chloride solution. The mixture was extracted with ethyl acetate and the separated organic layer was washed with water two times and brine subsequently. The organic phase was dried over anhydrous sodium sulfate and concentrated in vaccuo after filtration. The residue was purified by TLC (heptane/ethyl acetate 2:1) yielding the titled compound(19.6 mg, 73% yield) as a light yellow oil. ES-MS m/e: 466.1 (M+H+).

Workup

  1. customquenched by an addition of aq. ammonium chloride solution
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe separated organic layer was washed with water two times and brine subsequently
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vaccuo
  6. filtrationafter filtration
  7. customThe residue was purified by TLC (heptane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-27cc494ad8ec46dab54e1c08710097a0
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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