Ethanol → (S)-ethyl 1-(2-thiopheneacetyl)-3-hydroxymethylpiperidine

HRID 432826Notes

Reaction equation

HRID 432826 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([O:17]CC)=O)[CH2:10]1)=[O:8].[BH4-].[Na+].[CH2:22](O)[CH3:23]>ClCCl>[CH2:22]([C@H:10]1[CH:11]([CH2:15][OH:17])[CH2:12][CH2:13][CH2:14][N:9]1[C:7](=[O:8])[CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH3:23]

Participants

5

Reactant 3

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 9838651(S)-ethyl 1-(2-thiopheneacetyl)-3-piperidinecarboxylate

Product 1

HCID 86759306(S)-ethyl 1-(2-thiopheneacetyl)-3-hydroxymethylpiperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-ethyl 1-(2-thiopheneacetyl)-3-piperidinecarboxylate (1.053 g; 3.75 mmol) was dissolved in absolute ethanol (40 ml). Sodium borohydride (2 g; 52.9 mmol) was added and this mixture was heated to reflux. The mixture was allowed to reflux for 1 hour and was then cooled to ambient temperature, diluted with dichloromethane and carefully quenched and washed with 1 N HCl. The dichloromethane was separated, washed with saturated sodium chloride solution, dried with anhydrous potassium carbonate, and evaporated under reduced pressure at ambient temperature. The crude product was purified by chromatography on silica eluting with 100% ethyl acetate, giving (S)-ethyl 1-(2-thiopheneacetyl)-3-hydroxymethylpiperidine (715.5 mg) as a thick colorless oil. MS m/z (positive ion) 501 (dimer+Na+; 50), 488 (30), 262 (M+Na+; 75), 249 (50), 240 (MH+; 80), 102 (Et3NH+; 100).

Workup

  1. temperaturethis mixture was heated to reflux
  2. temperatureto reflux for 1 hour
  3. customcarefully quenched
  4. washwashed with 1 N HCl
  5. customThe dichloromethane was separated
  6. washwashed with saturated sodium chloride solution
  7. dry with materialdried with anhydrous potassium carbonate
  8. customevaporated under reduced pressure at ambient temperature
  9. customThe crude product was purified by chromatography on silica eluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-2bed498020bf4802b53494a2b8039064
Source dataset
uspto-grants-2003_12
Patent number
US06664271B1

Reaction notes

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