Hydrochloric Acid → (3As,4s,6s)-2-(dichloromethyl)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole

To a solution of CH2Cl2 (80 mL, 1.2 mol) in THF (800 mL) at −80° C. to −90° C. was added n-BuLi (2.5 M in hexane, 480 mL, 1.2 mol) under N2 and the reaction mixture was stirred for 1.5 h below −80° C. B(OEt)3 (200 mL, 1.2 mol) was added in one portion and the mixture was stirred for 1 h at −45° C. to −30° C. Aqueous HCl (5 M, 240 mL, 1.2 mol) was then added dropwise at temperature below −20° C. and the resulting mixture was stirred at −20° C. for 4 h. The organic layer was separated, and the water layer was extracted with Et2O (100 mL×2). The combined organic layer was dried over anhydrous Na2SO4 and concentrated to give an intermediate. The intermediate was re-dissolved in Et2O (800 mL), and pinanediol (188 g, 1.1 mol) was added to the solution. The reaction mixture was stirred overnight at room temperature and then concentrated in vacuo. The residue was purified by column chromatography (petroleum ether: ethyl acetate=10:1˜1:1) to afford intermediate 1 (190 g, 60% yield).

1. stirringthe mixture was stirred for 1 h at −45° C. to −30° C
2. stirringthe resulting mixture was stirred at −20° C. for 4 h
3. customThe organic layer was separated
4. extractionthe water layer was extracted with Et2O (100 mL×2)
5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
6. concentrationconcentrated
7. customto give an intermediate
8. stirringThe reaction mixture was stirred overnight at room temperature
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography (petroleum ether: ethyl acetate=10:1˜1:1)

ORD record

ord-a08d6cfbce2046ed97f8eb531b6f967c

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664200B2