Methyl iodide → 1-(1,1-Dimethylethyl) 2-methyl 5-oxo-1,2-piperidinedicarboxylate

HRID 626950Notes

Reaction equation

HRID 626950 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12](=[O:14])[CH2:11][CH2:10][CH:9]1[C:15]([OH:17])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:18](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.C(OCC)(=O)C>[O:14]=[C:12]1[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:9]([C:15]([O:17][CH3:18])=[O:16])[CH2:10][CH2:11]1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 11430Potassium CarbonateHCID 66777370HCID 66777370, compound

Product 1

HCID 695571871-(1,1-Dimethylethyl) 2-methyl 5-oxo-1,2-piperidinedicarboxylateYield 114.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(tert-Butoxycarbonyl)-5-oxopiperidine-2-carboxylic acid (2.0 g, 8.22 mmol) was dissolved in DMF (20 mL) under nitrogen and potassium carbonate (1.7 g, 12.33 mmol) was added, followed by iodomethane (620 μL, 9.95 mmol). The reaction mixture was stirred at room temperature under nitrogen for 23 h. Additional methyl iodide (256 μL, 4.11 mmol) was added and the reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (2×25 mL), then dried over sodium sulfate and concentrated to dryness. The crude residue was purified by flash column chromatography (Biotage), eluting with 0 to 100% ethyl acetate in heptanes, to afford the title compound (2.42 g, 53%) as a pale yellow oil. δH (250 MHz, CDCl3) 4.70 (dt, J 59.4, 6.3 Hz, 1H), 4.35 (dd, J 27.3, 19.0 Hz, 1H), 3.90 (dd, J 19.0, 12.4 Hz, 1H), 3.77 (s, 3H), 2.56-1.95 (m, 4H), 1.45 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 24 h
  2. washwashed with saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (2×25 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe crude residue was purified by flash column chromatography (Biotage)
  6. washeluting with 0 to 100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-003f18351e3049e3961f0ee07f2504eb
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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