Diisobutylaluminum hydride → HCID 10431207, compound

Temperature

0 °C

To 100 mg (0.28 mmol) of 1-9 in 3 mL of DMF at 0° C. was added 20 mg of NaH (0.6 mmol of a 60% suspension in oil), followed by 80 μL (0.6 mmol) of tert-butyl bromoacetate. After stirring for 2 h at 0° C., the reaction was quenched with a saturated NH4Cl solution, and extracted twice with EtOAc. The combined organic layers were then washed with brine, dried over Na2SO4, concentrated, and the residue purified by silica gel chromatography with EtOAc/hexanes to provide a colorless oil. This residue was dissolved in 10 mL of CH2Cl2, cooled to −78° C., and 900 μL of a 1M DIBAL-H solution in CH2Cl2 was added dropwise. After stirring for 45 min, the reaction was quenched with 500 μL of acetone, the cooling bath was removed, 15 mL of a 0.5 M tartaric acid solution was added, and the biphasic mixture was stirred for 1 h. The layers were separated, the organic was washed with water, dried over Na2SO4, and concentrated: The residue was then dissolved in 5 mL of THF and 1 mL of MeOH, and a small amount of NaBH4 was added. After stirring for 15 min, the reaction was quenched with 1M HCl, extracted twice with EtOAc, washed with brine, dried over Na2SO4, concentrated, and the residue purified by silica gel chromatography with EtOAc/hexanes to provide 2-2 as a sticky white taffy. Data for 2-2: 1HNMR (500 MHz, CDCl3) δ 7.4-7.2 (m, 5H), 7.1-6.9 (m, 3H), 6.4 (s, 1H), 4.8-4.6 (m, 3H), 4.2 (d, 1H), 3.8-3.7 (m, 2H), 3.7-3.5 (m, 2H), 2.85 (s, 6H) ppm. HRMS (ES) calc'd M+H for C22H24F2N2O3: 403.1828. Found: 403.1824.

1. customthe reaction was quenched with a saturated NH4Cl solution
2. extractionextracted twice with EtOAc
3. washThe combined organic layers were then washed with brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. customthe residue purified by silica gel chromatography with EtOAc/hexanes
7. customto provide a colorless oil
8. temperaturecooled to −78° C.
9. stirringAfter stirring for 45 min
10. customthe reaction was quenched with 500 μL of acetone
11. customthe cooling bath was removed
12. addition15 mL of a 0.5 M tartaric acid solution was added
13. stirringthe biphasic mixture was stirred for 1 h
14. customThe layers were separated
15. washthe organic was washed with water
16. dry with materialdried over Na2SO4
17. concentrationconcentrated
18. dissolutionThe residue was then dissolved in 5 mL of THF
19. addition1 mL of MeOH, and a small amount of NaBH4 was added
20. stirringAfter stirring for 15 min
21. customthe reaction was quenched with 1M HCl
22. extractionextracted twice with EtOAc
23. washwashed with brine
24. dry with materialdried over Na2SO4
25. concentrationconcentrated
26. customthe residue purified by silica gel chromatography with EtOAc/hexanes
27. customto provide 2-2 as a sticky white taffy

ORD record

ord-2a3101bc582f4486bf77c36d49a6779c

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07235580B2