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 RB flask equipped with overhead stirrer, thermocouple, and heating mantle. 2-Propanol (1.22 L) was added, followed by 610 mL of pH 7 0.1M potassium phosphate buffer. Buffer solution (610 mL) was charged to a 1.0 L erlenmeyer, and 2.44 g of NADP was added to the erlenmeyer 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 RT and triethylamine (50.2 mL, 360 mmol) was added. The resulting solution was aged at 40° C. for 1 h. The light slurry solution was cooled to RT, after which 122 g NaCl was added. The solution was aged at RT 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 RT then filtered and washed w/5:1 Hexanes:IPAc solution (150 mL). The solids were dried under vacuum at RT to provide 4-methyl-5-[(2R)-oxiran-2-yl]-2-benzofuran-1(3H)-one. 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J=8.1 Hz, 1H), 7.42 (d, J=8.1 Hz, 1H), 5.28 (s, 2H), 4.10 (dd, J=4.0, 2.8, 1H), 3.26 (dd, J=5.6, 4.0, 1H), 2.72 (dd, J=5.6, 2.8, 1H), 2.42 (s, 3H)

1. customequipped with overhead stirrer
2. temperaturethermocouple, and heating mantle
3. additionwas added to the erlenmeyer
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 RT
9. temperatureThe light slurry solution was cooled to RT
10. customwas aged at RT
11. extractionthen extracted 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 RT
19. filtrationthen filtered
20. washwashed w/5
21. customThe solids were dried under vacuum at RT

ORD record

ord-9f08d30237f24f659c11acf12f362836

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206199B2