تفاعل #657297

معادلة التفاعل

HCl

DCM

n-BuLi

pinanediol

B(OEt)3

→

Intermediate 1

المردود 65.7%

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

المردود 65.7%

المذيبات

THF

diethyl ether

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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).

المصدر