Ethyl formate → HCID 117970124, compound

HRID 2271313Notes

Reaction equation

HRID 2271313 reaction equation
[C:1]1([N:7]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][C:8]2=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].CC([N-]C(C)C)C.[CH2:23]([O:25]C=O)C.Cl[CH:29]1[CH:33]=[C:32]([CH3:34])[C:31](=[O:35])[O:30]1>O1CCCC1.C(OCC)(=O)C.O>[CH3:34][C:32]1[C:31](=[O:35])[O:30][CH:29]([O:25]/[CH:23]=[C:9]2/[C:8](=[O:14])[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:13][CH2:12][CH2:11][CH2:10]/2)[CH:33]=1

Participants

8

Reactant 4

HCID 8025Ethyl formateHCID 2724682Lithium diisopropylamideHCID 27540661-phenylazepan-2-oneHCID 125148665-Chloro-3-methylfuran-2(5H)-one

Product 1

HCID 117970124HCID 117970124, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

1-Phenylazepan-2-one (0.500 g, as prepared in Organic Letters 2000, pages 1101-1104) was dissolved in tetrahydrofuran (30 mL) and cooled to −78° C. To the solution was added LDA (2.0 mol/L in THF/heptane/ethylbenzene, 2.6 mL) dropwise. After stirring for 10 min between −55 and −50° C., the reaction mixture was warmed up to −40° C., stirred for 5 min and ethylformate (0.657 mL, 0.605 g) was added slowly. The mixture was warmed up to 0° C. and stirred for another 30 min. 2-Chloro-4-methyl-2H-furan-5-one (0.420 g in 2 mL of THF) was added dropwise. The reaction mixture was warmed up to room temperature and stirred for 3 h. Water and ethyl acetate were added and the layers were separated. The aqueous layer was extracted with ethyl acetate, the organic layers were combined, washed with water and brine, dried over Na2SO4 and the solvent was evaporated to give a brown residue which was purified by flash chromatography (0-100% ethyl acetate in cyclohexane). (3E)-3-[(4-methyl-5-oxo-2H-furan-2-yl)oxymethylene]-1-phenyl-azepan-2-one Ic-13 (0.103 g, 11%) was obtained as a white solid; mp: 150-160° C.; LCMS (Method D): 0.91 min; ES+314 (M+H+).

Workup

  1. temperaturethe reaction mixture was warmed up to −40° C.
  2. stirringstirred for 5 min
  3. temperatureThe mixture was warmed up to 0° C.
  4. stirringstirred for another 30 min
  5. temperatureThe reaction mixture was warmed up to room temperature
  6. stirringstirred for 3 h
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. washwashed with water and brine
  10. dry with materialdried over Na2SO4
  11. customthe solvent was evaporated
  12. customto give a brown residue which
  13. customwas purified by flash chromatography (0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-10add070db8b47538972f12ce1d018fc
Source dataset
uspto-grants-2015_09
Patent number
US09119398B2

Reaction notes

Loading…