Benzyl Bromide → 1-Benzyl-4-(2-trifluoromethoxy-phenyl)-1,2,3,6-tetrahydro-pyridine

HRID 505124Notes

Reaction equation

HRID 505124 reaction equation
[F:1][C:2]([F:17])([F:16])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(Cl)Cl.CO.[BH4-].[Na+]>C1(C)C=CC=CC=1.CO>[CH2:18]([N:13]1[CH2:12][CH:11]=[C:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[O:3][C:2]([F:1])([F:16])[F:17])[CH2:15][CH2:14]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 4311764Sodium borohydrideHCID 21226129Dichloromethane methanol2×HCID 463171664-(2-(Trifluoromethoxy)phenyl)pyridine

Product 1

HCID 667439831-Benzyl-4-(2-trifluoromethoxy-phenyl)-1,2,3,6-tetrahydro-pyridineYield 61%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(2-trifluoromethoxy-phenyl)-pyridine in toluene was added (1 eq.) benzyl bromide, and reaction mixture was stirred under reflux for 2 h. Reaction was monitored by TLC (CH2Cl2/MeOH 95:5) and revealed total conversion to the first intermediate. Complete evaporation of solvent gave a white solid which was pure enough to carry out the next step. The white solid was dissolved in MeOH under argon and cooled down to 0° C., (4 eq.) NaBH4 was added portion-wise (exothermic reaction). The reaction mixture was then stirred for 3 h at RT, reaction again monitored by TLC (CH2Cl2/MeOH 95:5) and revealed total conversion. Evaporation of MeOH, redissolution in CH2Cl2, and washing with 1N NaHCO3 then brine, and evaporation, followed by SiO2 gel chromatography (CH2Cl2/MeOH) gave the title compound in 61% yield.

Workup

  1. temperatureunder reflux for 2 h
  2. customReaction
  3. customComplete evaporation of solvent
  4. customgave a white solid which
  5. customportion-wise (exothermic reaction)
  6. stirringThe reaction mixture was then stirred for 3 h at RT
  7. customreaction
  8. customEvaporation of MeOH, redissolution in CH2Cl2
  9. washwashing with 1N NaHCO3
  10. custombrine, and evaporation

Sources & evidence

ORD record
ord-379df1357a0b43128d04f5c1d78eeb6a
Source dataset
uspto-grants-2010_08
Patent number
US07781436B2

Reaction notes

Loading…