1-Methylpiperidine-2,3-dione → 3-Ethynyl-3-hydroxy-1-methylpiperidin-2-one

HRID 1398525Notes

Reaction equation

HRID 1398525 reaction equation
[C:1]([Mg]Br)#[CH:2].[CH3:5][N:6]1[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[C:7]1=[O:13]>O1CCCC1>[C:1]([C:8]1([OH:12])[CH2:9][CH2:10][CH2:11][N:6]([CH3:5])[C:7]1=[O:13])#[CH:2]

Participants

4

Reactant 2

HCID 126685381-Methylpiperidine-2,3-dioneHCID 178418486HCID 178418486, compound

Product 1

HCID 866695763-Ethynyl-3-hydroxy-1-methylpiperidin-2-oneYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethynylmagnesium bromide (0.5M in tetrahydrofuran, 4 mL, 2 mmol) maintained under nitrogen at −20° C. was added a solution of 1-methylpiperidine-2,3-dione (220 mg, 0.87 mmol) in tetrahydrofuran (3 mL) dropwise with stirring within 1 min. The reaction mixture was stirred for 2 hr at room temperature and then quenched by the addition of saturated ammonium chloride solution (1 mL). The mixture was diluted with DCM (50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude residue was purified on a silica gel column, elution with ethyl acetate/petroleum ether (0:1-1:0) afforded the title compound (40 mg, 30%) as a brown oil: 1H NMR (400 MHz, CDCl3) delta 4.23 (s, 1H), 3.35-3.30 (m, 2H), 2.95 (s, 3H), 2.47 (s, 1H), 2.35-2.16 (m, 2H), 1.97-1.90 (m, 2H). LC-MS m/z=+154 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred for 2 hr at room temperature
  2. customquenched by the addition of saturated ammonium chloride solution (1 mL)
  3. additionThe mixture was diluted with DCM (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude residue was purified on a silica gel column, elution with ethyl acetate/petroleum ether (0:1-1:0)

Sources & evidence

ORD record
ord-d2dd33afe9514108a8274f70d20b3479
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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