Methanol → HCID 21955386, compound

HRID 2213028Notes

Reaction equation

HRID 2213028 reaction equation
B.O1CCCC1.Cl.C([C:11]1([CH2:24][C:25]([O:27][CH2:28]C)=[O:26])[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)(O)=O.CO>O1CCCC1>[C:18]1([CH2:17][N:14]2[CH2:13][CH2:12][C:11]3([CH2:28][O:27][C:25](=[O:26])[CH2:24]3)[CH2:16][CH2:15]2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuran2×HCID 86590576HCID 86590576, compound

Product 1

HCID 21955386HCID 21955386, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Borane-tetrahydrofuran complex (1.0M in tetrahydrofuran, 60 mL, 60 mmol) was added to a suspension of α-ethyl 4-carboxy-1-(phenylmethyl)-4-piperidineacetate hydrochloride (Helv. Chim. Acta 1972, 55, 2432–2438, 10.24 g, 30 mmol) in tetrahydrofuran (150 mL) and the mixture was stirred at room temperature for 3 days. Further borane-tetrahydrofuran complex (1.0M in tetrahydrofuran, 60 mL, 60 mmol) was added and the mixture was stirred at room temperature for 1 day. Methanol (20 mL) was added and the solvent was evaporated under reduced pressure. Methanol (200 mL) was added and the solvent was evaporated under reduced pressure. Methanol (200 mL) was added and the solvent was evaporated under reduced pressure. Hydrochloric acid (2M, 200 mL) was added and the mixture was heated under reflux for 4 hours. The mixture was cooled. Ether (200 mL) was added and the layers were separated. The organic layer was extracted with hydrochloric acid (2M, 2×100 mL) and the combined aqueous fractions were washed with ether (2×100 mL), adjusted to pH 10 with saturated aqueous potassium carbonate and extracted with dichloromethane (3×100 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2/MeOH/NH3(aq.) (96:4:0.4), to give the title compound (3.4 g, 46%). m/z (ES+) 246 (M+1).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 day
  2. customthe solvent was evaporated under reduced pressure
  3. additionMethanol (200 mL) was added
  4. customthe solvent was evaporated under reduced pressure
  5. additionMethanol (200 mL) was added
  6. customthe solvent was evaporated under reduced pressure
  7. additionHydrochloric acid (2M, 200 mL) was added
  8. temperaturethe mixture was heated
  9. temperatureunder reflux for 4 hours
  10. temperatureThe mixture was cooled
  11. additionEther (200 mL) was added
  12. customthe layers were separated
  13. extractionThe organic layer was extracted with hydrochloric acid (2M, 2×100 mL)
  14. washthe combined aqueous fractions were washed with ether (2×100 mL)
  15. extractionextracted with dichloromethane (3×100 mL)
  16. dry with materialThe combined organic fractions were dried (MgSO4)
  17. customthe solvent was evaporated under reduced pressure
  18. customThe residue was purified by flash column chromatography on silica gel
  19. washeluting with CH2Cl2/MeOH/NH3(aq.) (96:4:0.4)

Sources & evidence

ORD record
ord-5fca88cf2eb14fba9471d5180d9b0223
Source dataset
uspto-grants-2006_09
Patent number
US07105507B2

Reaction notes

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