Sodium hydride → HCID 67131413, compound

HRID 906892Notes

Reaction equation

HRID 906892 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[C@@H:10]([C@@H:21]([OH:23])[CH3:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=1>CN(C=O)C>[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[C@@H:10]([C@@H:21]([O:23][C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=2)[CH3:22])[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 66999546HCID 66999546, compound

Product 1

HCID 67131413HCID 67131413, compoundYield 88.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 88 mg (0.26 mmol) of (S)-1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol in DMF (6 mL) was added NaH (19 mg, 0.40 mmol). The reaction mixture was stirred at RT for 30 minutes, and then at 50° C. for 20 minutes. A solution of 6-chloro-nicotinonitrile (45 mg, 0.32 mmol) in DMF (2 mL) was added dropwise and stirring was continued 3 hours at 50° C. The reaction mixture was concentrated under vacuo. Extraction with EtOAc/H2O, followed by column chromatography (SiO2, EtOAc/H, 1:3) yielded 100 mg (87%) of the title compound as a colorless oil. ES-MS m/e: 436.2 (M+H+).

Workup

  1. waitat 50° C. for 20 minutes
  2. stirringstirring
  3. waitwas continued 3 hours at 50° C
  4. concentrationThe reaction mixture was concentrated under vacuo
  5. extractionExtraction with EtOAc/H2O

Sources & evidence

ORD record
ord-36a91f5553c84686bbaf59c65d132bab
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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