HCID 66758561, compound → HCID 66757870, compound

HRID 556968Notes

Reaction equation

HRID 556968 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)([O:14][CH3:15])[C:10](=[O:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][Mg]Br>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=2)([O:14][CH3:15])[C:10]([OH:23])([CH3:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 66758561HCID 66758561, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 66757870HCID 66757870, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-chloro-phenyl)-4-methoxy-3-oxo-piperidine-1-carboxylic acid tert-butyl ester (470 mg, 1.38 mmol) in anhydrous tetrahydrofuran (10 mL) at 0° C. was added methylmagnesium bromide (1.4 M in diethyl ether, 2.96 mL, 4.15 mmol) and the resulting mixture was stirred at that temperature for 3 h. Excess organomagnesium was quenched by the addition of saturated aqueous ammonium chloride and the reaction was allowed to warm to rt. To the biphasic mixture was added water and ethyl acetate. The phases were separated and the organic phase washed with brine, dried over magnesium sulfate, filtered, dried and concentrated to afford a crude residue which was purified by silica gel chromatography (100% methylene chloride −97.5% methylene chloride/2.5% methanol gradient) to afford pure 4-(4-chloro-phenyl)-3-hydroxy-4-methoxy-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (269 mg, 58%).

Workup

  1. customExcess organomagnesium was quenched by the addition of saturated aqueous ammonium chloride
  2. additionTo the biphasic mixture was added water and ethyl acetate
  3. customThe phases were separated
  4. washthe organic phase washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customdried
  8. concentrationconcentrated
  9. customto afford a crude residue which
  10. customwas purified by silica gel chromatography (100% methylene chloride −97.5% methylene chloride/2.5% methanol gradient)

Sources & evidence

ORD record
ord-cf30610ce0014ad6abbf5f2df1857425
Source dataset
uspto-grants-2011_11
Patent number
US08058287B2

Reaction notes

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