Acetic Acid → 3-(1-Propyl-piperidin-3-yl)-cyclohex-2-enone

HRID 890597Notes

Reaction equation

HRID 890597 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]([C:10]2[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH:11]=2)=[CH:5]1)[CH2:2][CH3:3].C(O)(=O)C.[BH3-]C#N.[Na+].C([O-])(O)=O.[Na+].Cl.[K+].[Br-]>C1COCC1.O>[CH2:1]([N:4]1[CH2:9][CH2:8][CH2:7][CH:6]([C:10]2[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH:11]=2)[CH2:5]1)[CH2:2][CH3:3]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 222458393-(1-Propyl-1,4,5,6-tetrahydro-pyridin-3-yl)-cyclohex-2-enone

Product 1

HCID 99645243-(1-Propyl-piperidin-3-yl)-cyclohex-2-enone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-(1-Propyl-1,4,5,6-tetrahydro-pyridin-3-yl)-cyclohex-2-enone (5.0 g, 22.8 mmol) (from b) above) was dissolved in THF (100 mL). At 0° C., acetic acid (1.38 mL, 22.8 mmol) was added followed by introduction of NaBH3CN (1.9 g, 30.0 mmol) in small portions maintaining the temperature. After the addition was complete the mixture was stirred for 1 h at this temperature and then at rt overnight. Work-up by addition of water (50 mL) and saturated aqueous NaHCO3 (50 mL) followed by extraction with dichloromethane (5×50 mL). The combined organic layers were dried (MgSO4) and evaporated. The residue was purified by column chromatography (silica, dichloromethane/ethanol 20:1) to give a colorless oil which was converted to the hydrochloride. Recrystallisation from isoprylether gave 4.2 g, 17.5 mmol (77%), mp 184–185° C. IR (KBr) 3396, 2941, 2469, 1667, 1455 cm−1; 1H-NMR (CDCl3) δ 5.83 (s, 1H), 3.85 (d, 2H), 2.29–2.56 (m, 7H), 1.23–2.17 (m, 10H), 0.88 (t, 3H) ppm; 13C-NMR (CDCl3) δ 198.4, 165.1, 123.4, 59.0, 55.6, 51.9, 41.6, 36.0, 27.3, 26.9, 22.8, 21.2, 17.6, 10.2 ppm; MS (EI) m/z 221 (M+).

Workup

  1. temperaturemaintaining the temperature
  2. additionAfter the addition
  3. customat rt
  4. customovernight
  5. extractionfollowed by extraction with dichloromethane (5×50 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by column chromatography (silica, dichloromethane/ethanol 20:1)
  9. customto give a colorless oil which
  10. customRecrystallisation from isoprylether
  11. customgave 4.2 g, 17.5 mmol (77%), mp 184–185° C

Sources & evidence

ORD record
ord-201244e90d424a978cd6c7ab7e48aa7b
Source dataset
uspto-grants-2006_02
Patent number
US06998405B2

Reaction notes

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