Reaction #2507827

Reaction equation

p-toluenesulfonyl cyanide

s-butyllithium

(R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman

→

(R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman-7-carbonitrile

Solvents

ether

THF

cyclohexane

THF

Conditions

Workup

1. 1
   workup.WAITleft
2. 2
   Otherdoes not exceed −65° C
3. 3
   workup.WAITAfter 1 h
4. 4
   Washwashed with dil. hydrochloric acid
5. 5
   Dryingphase is dried over sodium sulfate
6. 6
   Otherevaporated
7. 7
   Otherthe crude product is chromatographed on silica gel with toluene

Procedure

800 mg (1.68 mmol) of (R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman are dissolved in 30 ml of THF, and 1.7 ml (2.38 mmol) of a 1.4 M solution of s-butyllithium in cyclohexane are added at −50° C. The batch is warmed at −25° C. for 5 min, left to stir at −70° C. for 2 h, and a solution of 400 mg (2.21 mmol) of p-toluenesulfonyl cyanide in 10 ml of THF is subsequently added at such a rate that the temperature does not exceed −65° C. After 1 h, the batch is allowed to thaw, diluted with ether and washed with dil. hydrochloric acid. The org. phase is dried over sodium sulfate and evaporated, and the crude product is chromatographed on silica gel with toluene, giving (R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman-7-carbonitrile as colourless crystals of m.p. 111° C.

Source