Réaction #657297

Équation de réaction

HCl

DCM

n-BuLi

pinanediol

B(OEt)3

→

Intermediate 1

Rendement 65.7%

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

Rendement 65.7%

Solvants

THF

diethyl ether

Conditions de réaction

Traitement

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

Mode opératoire

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