Benzyl 4-oxopiperidine-1-carboxylate → HCID 67339986, compound

HRID 1675020Notes

Reaction equation

HRID 1675020 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.[O:15]=[C:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:18][CH2:17]1>CCOCC>[OH:15][C:16]1([C:7]2[CH:12]=[N:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)[CH2:17][CH2:18][N:19]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 27348955-Bromo-2-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 67339986HCID 67339986, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.6M in hexanes, 6.65 mL, 10.64 mmol) was added dropwise to 5-bromo-2-methoxypyridine (2.0 g, 10.64 mmol) in ether (30 mL) cooled to −78° C. over a period of 15 minutes. The resulting solution was stirred at −78° C. for 40 minutes then a solution of benzyl 4-oxo-1-piperidinecarboxylate (2.48 g, 10.64 mmol) in ether (10 mL) was added dropwise. The reaction was allowed to warm slowly to room temperature then quenched with ammonium chloride solution (50 mL) and extracted with EtOAc. The extract was washed sequentially with water and saturated brine, dried over MgSO4 and concentrated by evaporation then purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford benzyl 4-hydroxy-4-(6-methoxypyridin-3-yl)piperidine-1-carboxylate (1.90 g, 52%) as a pale orange oil.

Workup

  1. temperatureto warm slowly to room temperature
  2. customthen quenched with ammonium chloride solution (50 mL)
  3. extractionextracted with EtOAc
  4. washThe extract was washed sequentially with water and saturated brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated by evaporation
  7. customthen purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-e752080b59ae4b71a80c90e4e58b2237
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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