Acetonitrile → HCID 21904378, compound

HRID 988794Notes

Reaction equation

HRID 988794 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][NH:15][C:16](=O)[CH2:17][CH2:18][C:19]2[CH:24]=[CH:23]C=CC=2F)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)[F:30])=O.[C:34]([O-:37])([O-])=O.[K+].[K+].BrC[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.[OH-].[Na+].[CH3:51][C:52]#N>C(Cl)Cl>[F:30][C:23]1[CH:24]=[CH:19][CH:18]=[CH:17][C:16]=1[N:15]([CH2:14][CH:10]1[CH2:11][CH2:12][CH2:13][N:8]([CH2:6][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH2:9]1)[C:34](=[O:37])[CH2:51][CH3:52]

Participants

8

Reactant 6

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 7666Phenethyl bromideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 69593486HCID 69593486, compound

Product 1

HCID 21904378HCID 21904378, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-{[(2-fluorophenyl)propionylamino]methyl}piperidine-1-carboxylic acid tert-butyl ester (4) (162 mg, 0.45 mmol) in CH2Cl2 (1 ml) at 0° C. was added TFA (1 ml). After stirring for 30 min., solvent and excess TFA was removed by evaporation. The residue was dissolved in 1.5 ml of CH3CN (10 ml), to which K2CO3 (1245 mg) and (2-bromoethyl) benzene (123 μl, 0.9 mmol) were added. The mixture was stirred at 50° C. overnight. After cooling down to room temperature, 5 mL of 10% NaOH was added. The organic layer was separated. The aqueous layer was extracted with EtOAc (2×10 ml). The combined organic layers were washed with brine and dried with Na2SO4, filtered and evaporated. The crude product was purified by flash silica gel chromatography (5% MeOH in CH2Cl2) to give colorless N-(2-Fluorophenyl)-N-(1-Phenethylpiperidin-3-ylmethyl)propionamide (121) (141 mg, 85%). LRMS 369 (M+H+).

Workup

  1. customsolvent and excess TFA was removed by evaporation
  2. additionwere added
  3. stirringThe mixture was stirred at 50° C. overnight
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×10 ml)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash silica gel chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-94821da193e74773bc7842faa2115d46
Source dataset
uspto-grants-2003_10
Patent number
US06635661B2

Reaction notes

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