Реакция #61230

Уравнение реакции

1,4-dibromo-2-butene

mycophenolic acid methyl ester

sodium bis(trimethysilyl)amide

→

2-(4-bromo-but-2-enyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester

Выход 78.3%

Растворители

THF

THF

THF

Условия реакции

Обработка

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 10 minutes
3. 3
   workup.WAITstored at this temperature for 16 hours
4. 4
   ДругоеThe reaction was quenched with saturated aqueous ammonium chloride
5. 5
   ЭкстракцияThe mixture was extracted with ethyl acetate
6. 6
   Другоеto give
7. 7
   Другоеafter evaporation of the solvent
8. 8
   Другоеa residue that was purified by chromatography on silica gel eluting with ethyl acetate (0% to 40%)/hexanes

Методика

To a cooled (−78° C.) solution of mycophenolic acid methyl ester 4A (138 mg, 0.41 mmol) in THF (2.5 mL) was added a THF solution of sodium bis(trimethysilyl)amide (1.0 M, 0.98 mL). After stirring for 30 minutes, a solution of 1,4-dibromo-2-butene (950 mg, 4.1 mmol) in THF (2.5 mL) was added and stirring was continued for 10 minutes. The resulting mixture was warmed to −30° C. and stored at this temperature for 16 hours. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate to give, after evaporation of the solvent, a residue that was purified by chromatography on silica gel eluting with ethyl acetate (0% to 40%)/hexanes, affording 2-(4-bromo-but-2-enyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester 4B (150 mg, 78%) as an oil; 1H NMR (300 MHz, CDCl3) δ 1.75 (s, 3H), 2.0-2.4 (m, 8H), 2.62 (m, 1H), 3.37 (d, J=6.6 Hz, 2H), 3.58 (s, 3H), 3.76 (s, 3H), 3.88 (d, J=4.8 Hz, 2H), 5.1-5.3 (m, 3H), 5.67 (brs, 2H), 7.67 (s, 1H) ppm.

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