Tetrahydrofuran toluene → Ethyl 3-(4-hydroxypiperidin-1-YL)-3-methylpyrrolidine-1-carboxylate
Reaction equation
[C:1]([C:3]1([N:13]2[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15][CH2:14]2)[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4]1)#N.C[Mg]Br.C1(C)C=CC=CC=1.C1COCC1>O1CCCC1>[OH:19][CH:16]1[CH2:17][CH2:18][N:13]([C:3]2([CH3:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4]2)[CH2:14][CH2:15]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of ethyl 3-cyano-3-(4-hydroxy-1-piperidyl)pyrrolidine-1-carboxylate (1.0 gm, 3.74 mmol) in tetrahydrofuran (25 mL) was added a 1.4 M solution of methyl magnesium bromide in toluene/THF (5.35 mL, 7.48 mmol) at 0° C., and the mixture was allowed to warm to room temperature. The mixture was stirred for another 12 h at room temperature, the reaction was quenched with saturated ammonium chloride solution (5 mL) at 0° C. and diluted with ethyl acetate (25 mL). The layers were separated and the organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to afford the title compound as a pale solid (830 mg), which was used for the subsequent step without further purification. MS (M+1): 257.16.
Workup
- customthe reaction was quenched with saturated ammonium chloride solution (5 mL) at 0° C.
- additiondiluted with ethyl acetate (25 mL)
- customThe layers were separated
- washthe organic layer was washed with brine
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-9bd80f7fd2b14061af3d19f04db1766f
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119661B2
Reaction notes
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