(3RS,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide → 1-[(3SR,4RS)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanone

HRID 2191107Notes

Reaction equation

HRID 2191107 reaction equation
CON(C)[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH:7]1[C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)=[O:5].[CH3:27][Mg]Br>C1COCC1>[CH2:12]([N:9]1[CH2:10][CH2:11][CH:6]([C:4](=[O:5])[CH3:27])[CH:7]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH2:8]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 72299147(3RS,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amideHCID 178418573HCID 178418573, compound

Product 1

HCID 684757041-[(3SR,4RS)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

Under an inert atmosphere a 50 mL four necked flask (flame dried) with a magnetic stirrer was charged with 990 mg (2.65 mmol) (3SR,4RS)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide in 15 ml THF. The light yellow solution was cooled to −40° C. and 2.2 mL methylmagnesium bromide (3M in diethyl ether) was added drop wise over 5 min. The reaction was slowly warmed up to 0° C. over 2 h. The reaction mixture was quenched slowly with 20 mL aqueous NH4Cl-solution, diluted with 10 mL water and 10 mL ethyl acetate. The aqueous layer was separated and extracted once with 30 mL ethyl acetate. The combined organic layers were washed with 50 mL brine, dried over Na2SO4, filtered off and concentrated under vacuum and used without further purification in the consecutive step. MS (m/e): 327.2 [(M+H)+].

Workup

  1. temperatureThe reaction was slowly warmed up to 0° C. over 2 h
  2. customThe reaction mixture was quenched slowly with 20 mL aqueous NH4Cl-solution
  3. additiondiluted with 10 mL water and 10 mL ethyl acetate
  4. customThe aqueous layer was separated
  5. extractionextracted once with 30 mL ethyl acetate
  6. washThe combined organic layers were washed with 50 mL brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered off
  9. concentrationconcentrated under vacuum
  10. customused without further purification in the consecutive step

Sources & evidence

ORD record
ord-086f514ccebf4efcb9f61902c5af02bd
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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