Benzyl 4-oxopiperidine-1-carboxylate → HCID 67340546, compound

HRID 1675017Notes

Reaction equation

HRID 1675017 reaction equation
C([Mg]Cl)(C)C.[Cl-].[Li+].Br[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.[O:19]=[C:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22][CH2:21]1>C1COCC1>[OH:19][C:20]1([C:9]2[CH:10]=[N:11][CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=2)[CH2:21][CH2:22][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 111279913-Bromo-5-(trifluoromethyl)pyridineHCID 178461733HCID 178461733, compound

Product 1

HCID 67340546HCID 67340546, compoundYield 65.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Isopropylmagnesium chloride-lithium chloride complex (1.0M in THF) (5.31 mL, 5.31 mmol) was added dropwise to 3-bromo-5-(trifluoromethyl)pyridine (1.20 g, 5.31 mmol) in THF (10 mL) cooled to 0° C. over a period of 10 minutes. The resulting solution was stirred at 0° C. for 1 hour then benzyl 4-oxo-1-piperidinecarboxylate (1.24 g, 5.31 mmol) in THF (5 mL) was added dropwise. The mixture was allowed to warm slowly to room temperature and stirred for a further 1 hour before quenching with aqueous ammonium chloride (25 mL). The mixture was then extracted with tert butyl methyl ether. The extract was washed with water followed by saturated brine, dried over MgSO4, concentrated by evaporation then purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford benzyl 4-hydroxy-4-[5-(trifluoromethyl)pyridin-3-yl]piperidine-1-carboxylate (1.32 g, 65%) as a pale yellow oil.

Workup

  1. temperatureto warm slowly to room temperature
  2. stirringstirred for a further 1 hour
  3. custombefore quenching with aqueous ammonium chloride (25 mL)
  4. extractionThe mixture was then extracted with tert butyl methyl ether
  5. washThe extract was washed with water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated by evaporation
  8. customthen purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-fa06a263614c4d47b1ac544da346dcb0
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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