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

HRID 1660646Notes

Reaction equation

HRID 1660646 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-5d1306cb172c4a41842a3ee126dcedf8
Source dataset
uspto-grants-2011_10
Patent number
USRE042802E1

Reaction notes

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