5-Bromophthalide → 5-[1,3]dioxolan-2-ylmethyl-3H-isobenzofuran-1-one

Temperature

85 °C

A three-neck 5 L round bottomed flask equipped with a stir bar, firestone valve, thermocouple, condenser and heating mantle was charged with tri-t-butyl phosphonium tetrafluoroborate (500 mg, 1.72 mmol), palladium (II) acetate (250 mg, 1.1 mmol) and 5-bromo-2-benzofuran-1(3H)-one (100 g, 470 mmol). DMF (1.88 L) was added to the flask, and the mixture was degassed three times by alternating vacuum and nitrogen purge. Commercially available bromo(1,3-dioxolan-2-ylmethyl)zinc solution (1.03 L, 516 mmol) was added via canula and the mixture was again degassed three times. The mixture was then heated at 85° C. for 5 h. Analysis by HPLC-MS indicated the reaction was not complete. The mixture was stirred at 85° C. for 5 more h. The mixture was then allowed to return to room temperature for overnight. 2-methylTHF (2 L) and brine were added, and the mixture was stirred for 5 min. The layers were separated and the aqueous layer was extracted again with 2-methylTHF. The organic layers were combined, washed three times with brine (4 L each), dried over MgSO4, filtered, and concentrated. The crude product was purified by flash chromatography (1.5 kg silica cartridge), eluting with 0-20% ethyl acetate in dichloromethane to afford 5-(1,3-dioxolan-2-ylmethyl)-2-benzofuran-1(3H)-one. LC-MS (IE, m/z): 221 [M+1]+.

1. customA three-neck 5 L round bottomed flask equipped with a stir bar, firestone valve
2. temperaturethermocouple, condenser and heating mantle
3. customthe mixture was degassed three times
4. custompurge
5. customthe mixture was again degassed three times
6. addition2-methylTHF (2 L) and brine were added
7. stirringthe mixture was stirred for 5 min
8. customThe layers were separated
9. extractionthe aqueous layer was extracted again with 2-methylTHF
10. washwashed three times with brine (4 L each)
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude product was purified by flash chromatography (1.5 kg silica cartridge)
15. washeluting with 0-20% ethyl acetate in dichloromethane

ORD record

ord-6784f0c40b7d46e9a57c9fdbf4c4a27f

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952166B2