Hydrochloric Acid → (+)-4-(4-Fluorophenyl)-1,2,3,6-tetrahydro-1-(phenylmethyl)-3-pyridinemethanol

HRID 1858714Notes

Reaction equation

HRID 1858714 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:22]=[O:23].[OH-].[Na+]>O>[CH2:1]([N:8]1[CH2:9][CH:10]=[C:11]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH:12]([CH2:22][OH:23])[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 100615101-Benzyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine

Product 1

HCID 9912522(+)-4-(4-Fluorophenyl)-1,2,3,6-tetrahydro-1-(phenylmethyl)-3-pyridinemethanolYield 78.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

4.5 g (16.8 mmol) of 1-benzyl-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine were suspended in 55 ml of water, then partially dissolved by the addition of 70 ml of concentrated hydrochloric acid, 1.36 g (45.3 mmol) of paraformaldehyde were added and the mixture was stirred at 100° C. for 5 hours. After cooling to room temperature the mixture was adjusted to pH 5-6 with sodium hydroxide solution and the product was extracted twice with 100 ml of ethyl acetate. The organic phases were washed once with 100 ml of water, dried over magnesium sulphate, filtered and concentrated in a water-jet vacuum. The thus-obtained crude product was chromatographed on silica gel with hexane and ethyl acetate as the eluent (sic). There were obtained 3.91 g (78% of theory) of (RS)-[1-benzyl-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridin-3-yl]-methanol; MS: 297 (M)+.

Workup

  1. additionwere added
  2. temperatureAfter cooling to room temperature the mixture
  3. extractionthe product was extracted twice with 100 ml of ethyl acetate
  4. washThe organic phases were washed once with 100 ml of water
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in a water-jet vacuum
  8. customThe thus-obtained crude product
  9. customwas chromatographed on silica gel with hexane and ethyl acetate as the eluent (sic)

Sources & evidence

ORD record
ord-07ab4198d4664c73918535376e1146b3
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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