Water → HCID 59833627, compound

HRID 270098Notes

Reaction equation

HRID 270098 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:14][CH2:13][C:12]([CH2:16][C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2F)([OH:15])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN(C)C=O.O>C1(C)C=CC=CC=1>[CH2:3]([N:10]1[CH2:14][CH2:13][C:12]2([CH2:16][C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=3[O:15]2)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 576080171-Benzyl-3-(5-chloro-2-fluorobenzyl)pyrrolidin-3-ol

Product 1

HCID 59833627HCID 59833627, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a suspension of sodium hydride (NaH) (55%, 612 mg, 14.0 mmol) in toluene (10 mL) was added a solution of 1-benzyl-3-(5-chloro-2-fluorobenzyl)pyrrolidin-3-ol (1.3 g, 4.06 mmol) in toluene (20 mL) and the reaction mixture was kept on stirring at reflux, after 5 minutes dimethylformamide (10 mL) was added and the reaction mixture was refluxed for 90 minutes, cooled to room temperature, water (20 mL) was added and extracted with ethyl acetate. The organic layer was dried over sodium sulphate (Na2SO4), filtered, concentrated and the residue was purified by silica gel flash chromatography (0-1.5% methanol in dichloromethane, 0.2% ammonium hydroxide, NH4OH) to give the subtitled compound (560 mg).

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was refluxed for 90 minutes
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulphate (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel flash chromatography (0-1.5% methanol in dichloromethane, 0.2% ammonium hydroxide, NH4OH)

Sources & evidence

ORD record
ord-786ab0568e764394a6ced9b9f794aa82
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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