Реакция #217679

Уравнение реакции

N-phenyl-bis(trifluoromethanesulfonimide)

diethyl ether

n-butyllithiumhexane

hexamethyldisilazane

(1R,5R,6R)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester

→

(1R,5R,6R)-6-fluoro-bicyclo[3.1.0]hex-2-ene-2,6-dicarboxylic acid diethyl ester

Растворители

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Условия реакции

Обработка

1. 1
   Температураmaintained at −63° C. to −54° C
2. 2
   Температураat a temperature maintained at −63° C. to −52° C
3. 3
   Другое1 hour
4. 4
   Другоеlater at 63° C. to −45° C
5. 5
   workup.STIRRINGfurther stirred for 2.5 hours
6. 6
   Промывкаwashed three times with a saturated aqueous solution of sodium hydrogen carbonate
7. 7
   Сушкаwith a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate
8. 8
   ФильтрацияAfter the desiccant was filtered off
9. 9
   Концентрированиеthe filtrate was concentrated under reduced pressure
10. 10
    Другоеthe residue was purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=30:1 to 20:1 to 5:1)
11. 11
    workup.DISSOLUTIONThe obtained 175 g of (1R,5R,6R)-6-fluoro-2-trifluoromethanesulfonyloxybicyclo[3.1.0]hex-2-ene-6-carboxylic acid ethyl ester was dissolved in 875 mL of N,N-dimethylformamide
12. 12
    workup.ADDITION875 mL of ethanol, and after 95.1 mL of diisopropylethylamine, 8.65 g of triphenylphosphine and 3.70 g of palladium acetate were added
13. 13
    workup.STIRRINGthe mixture was stirred for 5.5 hours at room temperature, under a carbon monoxide atmosphere
14. 14
    workup.ADDITION1N hydrochloric acid was added
15. 15
    Экстракцияthe reaction solution was extracted six times with diethyl ether
16. 16
    Промывкаwashed four times with a saturated aqueous solution of sodium hydrogen carbonate
17. 17
    Сушкаwith a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate
18. 18
    ФильтрацияAfter the desiccant was filtered off
19. 19
    Концентрированиеthe filtrate was concentrated under reduced pressure
20. 20
    Другоеthe residue was purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=30:1 to 20:1 to 10:1)

Методика

245 mL of a solution of 2.66 M n-butyllithiumhexane was added dropwise to 700 mL of a solution of tetrahydrofuran containing 137 mL of hexamethyldisilazane and stirred for 1 hour at a temperature maintained at −63° C. to −54° C. 340 mL of a solution of tetrahydrofuran containing 101 g of (1R,5R,6R)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester was added dropwise thereto at a temperature maintained at −63° C. to −52° C. 700 mL of a solution of tetrahydrofuran containing 213 g of N-phenyl-bis(trifluoromethanesulfonimide) was added thereto 1 hour later at 63° C. to −45° C. The reaction solution was warmed naturally to room temperature and further stirred for 2.5 hours. The reaction solution was diluted with diethyl ether, washed three times with a saturated aqueous solution of sodium hydrogen carbonate and with a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=30:1 to 20:1 to 5:1). The obtained 175 g of (1R,5R,6R)-6-fluoro-2-trifluoromethanesulfonyloxybicyclo[3.1.0]hex-2-ene-6-carboxylic acid ethyl ester was dissolved in 875 mL of N,N-dimethylformamide and 875 mL of ethanol, and after 95.1 mL of diisopropylethylamine, 8.65 g of triphenylphosphine and 3.70 g of palladium acetate were added thereto, the mixture was stirred for 5.5 hours at room temperature, under a carbon monoxide atmosphere. 1N hydrochloric acid was added thereto, and the reaction solution was extracted six times with diethyl ether. The organic layers were combined, washed four times with a saturated aqueous solution of sodium hydrogen carbonate and with a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=30:1 to 20:1 to 10:1), thereby yielding 92.6 g of (1R,5R,6R)-6-fluoro-bicyclo[3.1.0]hex-2-ene-2,6-dicarboxylic acid diethyl ester.

Источник