Reaction #2358495

Reaction equation

2-Chloro-4-methyl-2H-furan-5-one

LDA

1-Phenylazepan-2-one

ethylformate

→

(3E)-3-[(4-methyl-5-oxo-2H-furan-2-yl)oxymethylene]-1-phenyl-azepan-2-one

Solvents

ethyl acetate

Water

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was warmed up to −40° C.
2. 2
   workup.STIRRINGstirred for 5 min
3. 3
   TemperatureThe mixture was warmed up to 0° C.
4. 4
   workup.STIRRINGstirred for another 30 min
5. 5
   TemperatureThe reaction mixture was warmed up to room temperature
6. 6
   workup.STIRRINGstirred for 3 h
7. 7
   Otherthe layers were separated
8. 8
   ExtractionThe aqueous layer was extracted with ethyl acetate
9. 9
   Washwashed with water and brine
10. 10
    Dryingdried over Na2SO4
11. 11
    Otherthe solvent was evaporated
12. 12
    Otherto give a brown residue which
13. 13
    Otherwas purified by flash chromatography (0-100% ethyl acetate in cyclohexane)

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+).

Source