Sodium hydride → HCID 67131755, compound

HRID 906907Notes

Reaction equation

HRID 906907 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C@@H:10]([C@@H:20]([OH:22])[CH3:21])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=1>CN(C=O)C>[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)[C@@H:10]([C@@H:20]([O:22][C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=2)[CH3:21])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 66999242HCID 66999242, compound

Product 1

HCID 67131755HCID 67131755, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 250 mg (0.79 mmol) of (S)-1-[(3R,4S)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-ethanol in DMF (10 mL) was added NaH (57 mg, 1.18 mmol). The reaction mixture was stirred at RT for 30 minutes, and then at 50° C. for 20 minutes. A solution of 2-chloro-5-trifluoromethyl-pyridine (172 mg, 0.95 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, 1:4) yielded 350 mg (96%) of the title compound as a colorless oil. ES-MS m/e: 461.3 (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-a5ebedec5c524995af8c3c7f82083040
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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