Methyl iodide → tert-Butyl 4-formyl-4-methylpiperidine-1-carboxylate

HRID 1400731Notes

Reaction equation

HRID 1400731 reaction equation
[CH:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)=[O:2].[CH3:16]C([O-])(C)C.[K+].CI>C(Cl)Cl.[Cl-].[Na+].O>[CH:1]([C:3]1([CH3:16])[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)=[O:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 22248051tert-Butyl 4-formyl-4-methylpiperidine-1-carboxylateYield 37.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of tert-butyl 4-formylpiperidine-1-carboxylate (4.5 g, 21.10 mmol) in CH2Cl2 (50 mL) at 0° C. was added t-BuOK (3.08 g, 27.4 mmol) followed by MeI (3.96 mL, 63.3 mmol) at 0° C. The resulting mixture was stirred 30 min, and then warmed to room temp and stirred for 1.5 h. The reaction mixture was then poured into brine and the mixture was extracted with dichloromethane, dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (0-20% EtOAc/hexane) to afford tert-butyl 4-formyl-4-methylpiperidine-1-carboxylate (1.8 g, 7.92 mmol, 37.5% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 9.48 (s, 1H), 3.71-3.66 (m, 2H), 3.19-3.05 (m, 2H), 1.93 (dt, J=13.7, 4.1 Hz, 2H), 1.47 (s, 9H), 1.46-1.37 (m, 2H), 1.10 (s, 3H). LCMS (M+H)=228.1.

Workup

  1. stirringstirred for 1.5 h
  2. extractionthe mixture was extracted with dichloromethane
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was then purified by Biotage (0-20% EtOAc/hexane)

Sources & evidence

ORD record
ord-495ded23ad204c3aa39c85fa4634efd6
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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