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

To a solution of DCM (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 while maintaining the 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 diethyl ether (100 mL×2). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to give an intermediate. The intermediate was re-dissolved in diethyl ether (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:EtOAc 10:1 to 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. temperaturewhile maintaining the temperature below −20° C.
3. stirringthe resulting mixture was stirred at −20° C. for 4 h
4. customThe organic layer was separated
5. extractionthe water layer was extracted with diethyl ether (100 mL×2)
6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
7. concentrationconcentrated
8. customto give an intermediate
9. stirringThe reaction mixture was stirred overnight at room temperature
10. concentrationconcentrated in vacuo
11. customThe residue was purified by column chromatography (petroleum ether:EtOAc 10:1 to 1:1)

ORD record

ord-3055904086fe40b8a59573b2b4ff6bec

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09023832B2