Potassium Carbonate → HCID 53959266, compound

HRID 257561Notes

Reaction equation

HRID 257561 reaction equation
[CH3:1][O:2][N:3]=[C:4]([CH2:10][C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(=O)([O-])[O-].[K+].[K+].[Br:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[C:26]([F:32])[CH:25]=1>CN(C=O)C>[Br:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][CH:10]([C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])[C:4](=[N:3][O:2][CH3:1])[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[C:26]([F:32])[CH:25]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27336604-Bromo-2-fluorobenzyl bromideHCID 53883597HCID 53883597, compound

Product 1

HCID 53959266HCID 53959266, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 5.0 g (21.8 mmol) of ethyl 2-methoxyimino-4-oxooctanoate (from Example 1, Step A), 3.6 g (26 mmol) of anhydrous potassium carbonate, and 70 mL of dry DMF was stirred under N2 at room temperature for 1 hour. The mixture was then cooled to 0° C. and treated dropwise with a solution of 5.9 g (21.8 mmol) of 4-bromo-2-fluorobenzyl bromide in 20 mL of dry DMF. The mixture was allowed to warm slowly to room temperature and was stirred under N2 for 48 hours. The mixture was partitioned between 400 mL of ethyl acetate and 400 mL of 0.2N HCl. The organic layer was washed twice with H2O and then dried over Na2SO4. The filtered solution was concentrated, and the residual oil was flash chromatographed on silica gel. Gradient elution with 5-20% ethyl acetate in hexane afforded 3.51 g (39%) of the title compound as an oil; homogeneous by TLC in 3:1 hexane-EtOAc; mass spectrum (FAB) m/e 416, 418 (M+1)+. 200 MHz 1H NMR (CDCl3) δ0.87 (t, J=7.1 Hz, 3H), 1.2-1.4 (m, 5H) including 1.25 (t, J=7.1 Hz, 3H), 1.55 (m, 2H), 2.31 (t, J=7.1 Hz, 2H), 2.97 (dd, J=14, 10 Hz, 1H), 3.36 (dd, J=14, 5 Hz, 1H), 3.95 (s, 3H), 4.15-4.35 (m, 3H), 6.98 (dd, J≈8, 8 Hz, 1H), 7.15 (apparent d, J=8.2 Hz, 2H).

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. temperatureto warm slowly to room temperature
  3. stirringwas stirred under N2 for 48 hours
  4. customThe mixture was partitioned between 400 mL of ethyl acetate and 400 mL of 0.2N HCl
  5. washThe organic layer was washed twice with H2O
  6. dry with materialdried over Na2SO4
  7. concentrationThe filtered solution was concentrated
  8. customchromatographed on silica gel
  9. washGradient elution with 5-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-02c05a7061244479af4a0830c7395c16
Source dataset
uspto-grants-1993_11
Patent number
US05262412

Reaction notes

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