تفاعل #61888

معادلة التفاعل

7-hydroxy-6-(4-hydroxy-3-methyl-but-2-enyl)-5-methoxy-4-methyl-3H-isobenzofuran-1-one

diisopropyl bromomethylphosphonate

lithium t-butoxide

→

[4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyloxymethyl]-phosphonic acid diisopropyl ester

المردود 32.0%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction was quenched with 1N HCl
2. 2
   workup.ADDITIONThe mixture was poured into 5% aqueous lithium chloride
3. 3
   استخلاصextracted with ethyl acetate
4. 4
   تركيزconcentrated
5. 5
   أخرىThe residue was purified by chromatography on silica gel

الإجراء التجريبي

A mixture of 7-hydroxy-6-(4-hydroxy-3-methyl-but-2-enyl)-5-methoxy-4-methyl-3H-isobenzofuran-1-one 156A (50 mg, 0.18 mmol, Pankiewicz et al., J. Med. Chem., 45, 703), diisopropyl bromomethylphosphonate (93 mg, 0.36 mmol) and lithium t-butoxide (1M in THF, 0.54 mL) in DMF (3 mL) was heated at 70° C. for 5 hours. The reaction was quenched with 1N HCl. The mixture was poured into 5% aqueous lithium chloride, extracted with ethyl acetate, and concentrated. The residue was purified by chromatography on silica gel, affording [4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyloxymethyl]-phosphonic acid diisopropyl ester 156B (25 mg, 32%); 1H NMR (300 MHz, CDCl3) δ1.25 (m, 12H), 1.79 (s, 3H), 2.05 (s, 3H), 3.37 (d, J=6.6 Hz, 2H), 3.58 (d, 2H), 3.77 (s, 3H), 3.97 (m, 2H), 4.68 (m, 2H), 5.19 (s, 2H), 5.45 (t, J=6.6 Hz, 1H), 7.83 (s, 1H) ppm.

المصدر