Diisobutylaluminumhydride → HCID 89872641, compound

Temperature

-78 °C

A solution of 5-(benzyloxy)-7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (Example 1B, 6.76 g, 21.5 mmol) in dichloromethane (120 mL) was cooled to −78° C. and treated with 43 mL (64.5 mmol) of a 1.5 M solution of diisobutylaluminum hydride in toluene added dropwise over 20 min. The resulting mixture was then stirred at −78° C. for 3 h. The reaction mixture was quenched by the careful addition of methanol (5 mL) added dropwise over 15 min, followed by 1N hydrochloric acid (50 mL) added dropwise over 15 min. The cooling bath was then removed and an additional 150 mL of 1N hydrochloric acid was added over 20 min. The mixture was then stirred at 22° C. for 2 h and diluted with dichloromethane (400 mL). The organic phase was collected and the aqueous phase (pH ˜1) was extracted with dichloromethane (3×50 mL). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residual oil was diluted with tetrahydrofuran (70 mL), treated with 10 mL of 0.1N hydrochloric acid and stirred at 20° C. for 2 h. The reaction mixture was diluted with ethyl acetate (300 mL), washed with brine, dried over anhydrous magnesium sulfate, evaporated in vacuo to give a clear oil. Chromatography on silica gel (4×13 cm, elution toluene) gave 4.08 g (73% yield) of the title aldehyde as a clear oil which solidified on standing. LC (Method C): 2.237 min. HRMS (ESI) calcd for C15H15O4 [M+H]+ m/z 259.0965. found 259.1153. 1H NMR (CDCl3, 600 MHz) δ 3.80 (s, 3H), 5.07 (s, 2H), 5.97 (d, J=2.1 Hz, 1H), 6.01 (d, J=2.1 Hz, 1H), 7.3-7.4 (m, 5H), 10.15 (s, 1H), 12.49 (s, 1H).

1. additionadded dropwise over 20 min
2. customThe reaction mixture was quenched by the careful addition of methanol (5 mL)
3. additionadded dropwise over 15 min
4. additionadded dropwise over 15 min
5. customThe cooling bath was then removed
6. additionan additional 150 mL of 1N hydrochloric acid was added over 20 min
7. stirringThe mixture was then stirred at 22° C. for 2 h
8. additiondiluted with dichloromethane (400 mL)
9. customThe organic phase was collected
10. extractionthe aqueous phase (pH ˜1) was extracted with dichloromethane (3×50 mL)
11. washThe combined organic extracts were washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated in vacuo
14. additionThe residual oil was diluted with tetrahydrofuran (70 mL)
15. additiontreated with 10 mL of 0.1N hydrochloric acid
16. stirringstirred at 20° C. for 2 h
17. additionThe reaction mixture was diluted with ethyl acetate (300 mL)
18. washwashed with brine
19. dry with materialdried over anhydrous magnesium sulfate
20. customevaporated in vacuo
21. customto give a clear oil

ORD record

ord-1d0d107095d74c3890587bf00c155032

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927688B2