Benzyl Bromide → (1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanol

HRID 1940560Notes

Reaction equation

HRID 1940560 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[CH2:9](Br)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[BH4-].[Na+]>CN(C)C=O.C(O)C>[CH2:9]([N:6]1[CH2:7][CH:8]=[C:3]([CH2:2][OH:1])[CH2:4][CH2:5]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 114724-HydroxymethylpyridineHCID 4311764Sodium borohydride

Product 1

HCID 11264156(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanol

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-hydroxymethylpyridine (20 g, 0.183 mol) in anhydrous dimethylformamide (70 ml) was treated with benzyl bromide (24 ml, 0.202 mol) and the mixture was stirred at 100° C. for two hours. The reaction was cooled to room temperature and diluted with absolute ethanol (250 ml). Sodium borohydride (8.7 g, 0.229 mol) was added portionwise and the mixture stirred at reflux for 3 hours. The solvent was evaporated in vacuo and the residue partitioned between dichloromethane and water. The organic phase was separated, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed with 1:1 hexane/ethyl acetate as eluant to the title compound (13 g, 35%) as a lemon yellow solid; δH (CDCl3) 2.12-2.20 (2H, m, tetrahydropyridinyl CH2), 2.60 (2H, t, J 7.5 Hz, tetrahydropyridinyl CH2), 2.96-3.04 (2H, m, tetrahydropyridyl CH2), 3.60 (2H, s, PhCH2N), 4.00-4.04 (2H, m, CH2OH), 5.60-5.66 (1H, m, tetrahydropyridinyl 5-H), and 7.20-7.40 (5H, m, ArH). m/z (CI+, NH3) 204 (M+1)+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. stirringthe mixture stirred
  3. temperatureat reflux for 3 hours
  4. customThe solvent was evaporated in vacuo
  5. customthe residue partitioned between dichloromethane and water
  6. customThe organic phase was separated
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was chromatographed with 1:1 hexane/ethyl acetate as eluant to the title compound (13 g, 35%) as a lemon yellow solid

Sources & evidence

ORD record
ord-5d6c1e6047ea4795943e2dc3b2df55f8
Source dataset
uspto-grants-1997_12
Patent number
US05700809

Reaction notes

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