Reaction #657297

Reaction equation

HCl

DCM

n-BuLi

pinanediol

B(OEt)3

→

Intermediate 1

Yield 65.7%

(3aS,4S,6S)-2-(dichloromethyl)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole

Yield 65.7%

Solvents

THF

diethyl ether

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred for 1 h at −45° C. to −30° C
2. 2
   Temperaturewhile maintaining the temperature below −20° C.
3. 3
   workup.STIRRINGthe resulting mixture was stirred at −20° C. for 4 h
4. 4
   OtherThe organic layer was separated
5. 5
   Extractionthe water layer was extracted with diethyl ether (100 mL×2)
6. 6
   DryingThe combined organic layers were dried over anhydrous Na2SO4
7. 7
   Concentrationconcentrated
8. 8
   Otherto give an intermediate
9. 9
   workup.STIRRINGThe reaction mixture was stirred overnight at room temperature
10. 10
    Concentrationconcentrated in vacuo
11. 11
    OtherThe residue was purified by column chromatography (petroleum ether:EtOAc 10:1 to 1:1)

Procedure

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).

Source