Tert-butyl 3-cyano-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylate → Tert-butyl 3-methyl-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylate

HRID 406501Notes

Reaction equation

HRID 406501 reaction equation
[C:1]([C:3]1([N:15]2[CH2:20][CH2:19][CH:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1)#N.C[Mg]Br>C1COCC1>[CH3:1][C:3]1([N:15]2[CH2:20][CH2:19][CH:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4]1

Participants

4

Reactant 2

HCID 68900743Tert-butyl 3-cyano-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 68900797Tert-butyl 3-methyl-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylateYield 96.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of tert-butyl 3-cyano-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylate (1.2 g, 3.38 mmol) in THF (16 mL) was added a solution of methylmagnesium bromide (1.4M in THF, 12.06 mL) dropwise. The mixture was stirred at ambient temperature for about 2.5 h, cooled to about 0° C. and quenched by the dropwise addition of saturated ammonium chloride solution. The organic phase was separated, washed with water (2×75 mL) and brine (50 mL), dried over magnesium sulfate and concentrated under reduced pressure to yield tert-butyl 3-methyl-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylate (1.12 g, 3.25 mmol) as a yellow solid. HPLC (Table 1, Method f) Rt 5.01 min; m/z: (M+H)+ 345.

Workup

  1. temperaturecooled to about 0° C.
  2. customquenched by the dropwise addition of saturated ammonium chloride solution
  3. customThe organic phase was separated
  4. washwashed with water (2×75 mL) and brine (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7a1c0dfca8fb4dc7853d57b4da4951cf
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

Loading…