Sodium Chloride → 4-Methyl-5-((2R)-oxiran-2-yl)-2-benzofuran-1(3H)-one

Temperature

28 °C

5-(2-Bromo-acetyl)-4-methyl-3H-isobenzofuran-1-one (48.8 g, 181 mmol) was charged to a 5 L 3 neck round bottom equipped with overhead stirrer, thermocouple, and heating mantle. 2-Propanol (1.22 L) was added, followed by 610 mL of pH 7.1M potassium phosphate buffer. Buffer solution (610 mL) was charged to a 1.0 L Erlenmeyer flask, and 2.44 g of NADP was added to the Erlenmeyer flask and swirled to dissolve. A reducing enzyme, KRED MIF-20 (2.44 g) (available from Codexis, Inc., 200 Penobscot Drive, Redwood City, Calif. 94063, www.codexis.com, tel. 1-650-421-8100) was added to the Erlenmeyer flask and the mixture was swirled to dissolve the solids. The resulting solution was added to the 5 L round bottom, which was then heated to 28° C. and aged for 6 hours, at which point the reaction was cooled to room temperature, and triethylamine (50.2 mL, 360 mmol) was added. The resulting solution was aged at 40° C. for 1 hour. The light slurry solution was cooled to room temperature, after which 122 g NaCl was added. The solution was aged at room temperature and then extracted with 1.22 L isopropyl acetate (IPAc). The aqueous layer was re-extracted with 400 mL IPAc and the combined organics were washed with 400 mL 20% brine solution, dried over MgSO4, filtered and concentrated by rotary evaporation. The resulting solids were taken up in 100 mL IPAc (thick slurry). Hexanes were added (400 mL) and the suspension aged at room temperature and then filtered and washed w 5:1 Hexanes:IPAc solution (150 mL). The crystalline solids were dried under vacuum at room temperature to provide 4-methyl-5-[(2R)-oxiran-2-yl]-2-benzofuran-1(3H)-one.

1. customequipped with overhead stirrer
2. temperaturethermocouple, and heating mantle
3. additionwas added to the Erlenmeyer flask
4. dissolutionto dissolve
5. additionwas added to the Erlenmeyer flask
6. dissolutionto dissolve the solids
7. additionThe resulting solution was added to the 5 L round bottom
8. temperaturewas cooled to room temperature
9. temperatureThe light slurry solution was cooled to room temperature
10. customwas aged at room temperature
11. extractionextracted with 1.22 L isopropyl acetate (IPAc)
12. extractionThe aqueous layer was re-extracted with 400 mL IPAc
13. washthe combined organics were washed with 400 mL 20% brine solution
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. concentrationconcentrated by rotary evaporation
17. additionHexanes were added (400 mL)
18. customaged at room temperature
19. filtrationfiltered
20. washwashed w 5:1 Hexanes
21. customThe crystalline solids were dried under vacuum at room temperature

ORD record

ord-a4528883731a427fa0b1b4ef5e83f79b

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108947B2