Tetrahydrofuran → HCID 58080767, compound

Temperature

65 °C

A solution of TMSCHN2 (2 M in hexanes, 36.0 mL, 72.0 mmol) is added to a stirred room temperature solution of acid 10-33 (9.99 g, 36.02 mmol) in a 1:1 mixture of PhMe/MeOH (134 mL). After 1.5 h, the mixture is quenched with glacial AcOH (10 mL) and stirred for an additional 5 min. The solvents are removed in vacuo to provide the crude ester as a solid upon standing. The intermediate ester (15.2 g, 52.1 mmol) is dissolved in THF (200 mL) and treated with LAH powder (4.95 g, 130 mmol). The resulting slurry is heated to 65° C. for 3 h, then cooled to room temperature and slowly quenched with water (3.6 mL). The mixture is then treated with 2 N NaOH (3.6 mL), followed by additional water (10.8 mL). The resulting slurry is stirred for 1 h, then filtered to remove solids. The filtrate is dried over Na2SO4, filtered again, and concentrated in vacuo to provide the desired product. The solids initially collected by filtration are resuspended in acetone and vigorously stirred overnight at room temperature. The slurry is refiltered, and the remaining acetone is combined with the initially collected product. Concentration of the combined organic filtrates provides the desired intermediate 10-34 (7.50 g).

1. customthe mixture is quenched with glacial AcOH (10 mL)
2. customThe solvents are removed in vacuo
3. customto provide the crude ester as a solid
4. temperaturecooled to room temperature
5. customslowly quenched with water (3.6 mL)
6. additionThe mixture is then treated with 2 N NaOH (3.6 mL)
7. stirringThe resulting slurry is stirred for 1 h
8. filtrationfiltered
9. customto remove solids
10. dry with materialThe filtrate is dried over Na2SO4
11. filtrationfiltered again
12. concentrationconcentrated in vacuo

ORD record

ord-ca473b2b30f4440da963ed43e2f94e52

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569339B2