Tert-butyl 3-oxopiperidine-1-carboxylate → HCID 66784471, compound

HRID 1096667Notes

Reaction equation

HRID 1096667 reaction equation
[C:1]([C:5]1[N:9]([CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:8]=[N:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[C:20]([N:27]1[CH2:32][CH2:31][CH2:30][C:29](=[O:33])[CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>C1COCC1>[C:1]([C:5]1[N:9]([CH2:10][CH2:11][CH2:12][O:13][CH3:14])[C:8]([C:29]2([OH:33])[CH2:30][CH2:31][CH2:32][N:27]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:28]2)=[N:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 66786128HCID 66786128, compoundHCID 178418339Butyllithium

Product 1

HCID 66784471HCID 66784471, compoundYield 21.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Into a 50 mL round bottomed flask was added 5-tert-butyl-1-(3-methoxypropyl)-1H-imidazole (133A) (376 mg, 1.9 mmol) and THF (9.6 mL). The solution was cooled to −78° C. and n-BuLi (843 μL, 2.5 M/hexanes, 2.1 mmol) was added slowly via syringe. The mixture was stirred for 20 minutes and slowly warmed to −30° C. The solution was cooled to −78° C. and N-Boc-3-piperidone (418 mg, 2.1 mmol) in THF (5 mL) was added slowly via syringe; the mixture was allowed to warm to room temperature overnight. Solvent was removed under vacuum and the residue was partitioned between water (25 mL) and ethyl acetate (25 mL). The organic layer was separated and discarded. The aqueous layer extracted with ethyl acetate (2×25 mL). The organic portions were combined and washed with brine (50 mL) and dried over sodium sulfate and filtered. The solvent was removed in vacuo and the residue was purified by preparatory LC/MS (10-45% CH3CN in H2O) to give tert-butyl 3-(5-tert-butyl-1-(3-methoxypropyl)-1H-imidazol-2-yl)-3-hydroxypiperidine-1-carboxylate (133B) as a yellow oil (160 mg, 21% yield). ESI-MS:m/z 396.5 (M+H)+.

Workup

  1. temperatureslowly warmed to −30° C
  2. temperatureThe solution was cooled to −78° C.
  3. temperatureto warm to room temperature overnight
  4. customSolvent was removed under vacuum
  5. customthe residue was partitioned between water (25 mL) and ethyl acetate (25 mL)
  6. customThe organic layer was separated
  7. extractionThe aqueous layer extracted with ethyl acetate (2×25 mL)
  8. washwashed with brine (50 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customThe solvent was removed in vacuo
  12. customthe residue was purified by preparatory LC/MS (10-45% CH3CN in H2O)

Sources & evidence

ORD record
ord-578917433e474437b9af9579f1f3c0b6
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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