Methyl iodide → HCID 54724307, compound

HRID 1436871Notes

Reaction equation

HRID 1436871 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([C:13]([NH:16][C:17](=[O:23])[C:18]([O:20]CC)=O)([CH3:15])[CH3:14])[CH2:9][C:8]2=[O:24])=[CH:4][CH:3]=1.[Li+].[CH3:28][Si]([N-][Si](C)(C)C)(C)C.CI>CN(C=O)C>[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]3[C:9](=[C:18]([OH:20])[C:17](=[O:23])[N:16]([CH3:28])[C:13]3([CH3:14])[CH3:15])[C:8]2=[O:24])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium Hexamethyldisilazide3×HCID 91285473HCID 91285473, compound

Product 1

HCID 54724307HCID 54724307, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of ethyl ({1-[1-(4-fluorobenzyl)-2-oxopiperidin-4-yl]-1-methyethyl}amino)(oxo)acetate (1.2 g, 3.3 mmol) in anhydrous DMF (10 mL) under an atmosphere of nitrogen was added LiHMDS (1M in THF, 3.5 mL, 3.5 mmol). After stirring at 0° C. for 15 min, methyl iodide (0.47 g, 3.3 mmol) was added to the reaction mixture. After stirring for an additional 15 min, more LiHMDS (1M in THF, 3.5 mmol, 3.5 mmol) was added. After another 2 h, an additional portion of LiHMDS (1M in THF, 3.5 mL, 3.5 mmol) was added. After stirring at room temperature for 24 hours, the reaction mixture was concentrated under vacuum. The residual material was purified using reverse phase HPLC on a C18 stationary phase eluting with a gradient of 5%-95% acetonitrile (0.1% TFA) in H2O (0.1% TFA) to afford the title compound as an oil 1H NMR (400 MHz, CDCl3) δ 7.27 (m, 2H), 7.04 (t, J=8.6 Hz, 2H), 4.67 (d, J=14.7 Hz, 1H), 4.52 (d, J=14.7 Hz, 1H), 3.33 (d, J=6 Hz, 2H), 3.31 (s, 3H), 2.84 (m, 1H), 1.93 (m, 1H), 1.64 (m, 1H), 1.37 (s, 3H), 1.13 (s, 3H) ppm. ES MS M+1=333.

Workup

  1. stirringAfter stirring for an additional 15 min
  2. waitAfter another 2 h
  3. stirringAfter stirring at room temperature for 24 hours
  4. concentrationthe reaction mixture was concentrated under vacuum
  5. customThe residual material was purified
  6. washeluting with a gradient of 5%-95% acetonitrile (0.1% TFA) in H2O (0.1% TFA)

Sources & evidence

ORD record
ord-d3b20dacf61247919932d7182fbc531c
Source dataset
uspto-grants-2009_11
Patent number
US07619086B2

Reaction notes

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