Tetrahydrofuran → trans 1-Benzyl-4-(4-fluorophenyl)-3-piperidinemethanol

HRID 2296764Notes

Reaction equation

HRID 2296764 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10](CC(O)=O)[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:26]1CCC[CH2:27]1>>[CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]([CH2:27][OH:26])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 18335032HCID 18335032, compound

Product 1

HCID 10881101trans 1-Benzyl-4-(4-fluorophenyl)-3-piperidinemethanolYield 92%

Procedure

A solution of trans (4R)-1-benzyl-3-carboxymethyl-4-(4′-fluorophenyl)-piperidine-2-one (1.97 g) in tetrahydrofuran (20 ml) was treated with borane-tetrahydrofuran complex (19.6 ml, 1 molar) and heated at reflux for 6 hours. After cooling, the reaction was quenched with 1 molar hydrochloric acid, then stirred and heated at reflux for a further 1 hour. The mixture was cooled to ambient temperature, the pH adjusted to 9 with 1 molar sodium hydroxide, and extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with saturated sodium chloride and evaporated to give trans-(4R)-1-benzyl-4-(4′-fluorophenyl)-3-hydroxymethylpiperidine (1.59 g, 92%).

Workup

  1. temperatureheated
  2. temperatureat reflux for 6 hours
  3. temperatureAfter cooling
  4. customthe reaction was quenched with 1 molar hydrochloric acid
  5. temperatureheated
  6. temperatureat reflux for a further 1 hour
  7. extractionextracted with ethyl acetate (3×20 ml)
  8. washThe combined organic extracts were washed with saturated sodium chloride
  9. customevaporated

Sources & evidence

ORD record
ord-0053598c9c4e41d29977491258691af3
Source dataset
uspto-grants-2002_12
Patent number
US06489347B1

Reaction notes

Loading…