Sodium Hydroxide → 4-(4-Methoxyphenyl)-1,2,3,6-tetrahydropyridine

HRID 1940539Notes

Reaction equation

HRID 1940539 reaction equation
O[C:2]1([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][N:5](C(=O)C)[CH2:4][CH2:3]1.[OH-].[Na+]>Cl>[CH3:18][O:17][C:14]1[CH:13]=[CH:12][C:11]([C:2]2[CH2:7][CH2:6][NH:5][CH2:4][CH:3]=2)=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 214629681-(4-Hydroxy-4-[4-methoxyphenyl]piperidin-1-yl)ethanone

Product 1

HCID 135448404-(4-Methoxyphenyl)-1,2,3,6-tetrahydropyridineYield 24%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

1-(4-Hydroxy-4-[4-methoxyphenyl]piperidin-1-yl )ethanone (14.75 g, 59 mmol) was dissolved in hydrochloric acid (250 mg, 6M) and refluxed for 12 hours. The reaction mixture was cooled in ice and basified with sodium hydroxide solution (155 ml, 10M), then extracted with dichloromethane (2×500 ml). The extractions were combined, dried (MgSO4), and concentrated in vacuo. The crude product was purified by flash chromatography eluting with 10% methanol in dichloromethane, containing 1% aqueous ammonia. Concentration of the appropriate fractions gave 4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine (2.65 g, 24%) as a tan solid; δH (DMSO-d6) 2.3 (2H, m, tetrahydropyridinyl CH2), 2.9 (2H, t, J 5.6 Hz, tetrahydropyridinyl CH2), 3.4 (2H, d, J 3.4 Hz, tetrahydropyridinyl CH2), 3.7 (3H, s, ArOCH3), 6.1 (1H, m, CH=CR), 6.9 (2H, d, J 9.6 Hz, ArH), 7.3 (2H, d, J 9.6 Hz, ArH), and 9.6 (1H, br s, NH).

Workup

  1. temperaturerefluxed for 12 hours
  2. temperatureThe reaction mixture was cooled in ice
  3. extractionextracted with dichloromethane (2×500 ml)
  4. extractionThe extractions
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography
  8. washeluting with 10% methanol in dichloromethane
  9. additioncontaining 1% aqueous ammonia

Sources & evidence

ORD record
ord-d13a2da74f824fc7889fb36f2b9d109f
Source dataset
uspto-grants-1997_12
Patent number
US05700809

Reaction notes

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