Reaction #5803

Reaction equation

diethyl ether

t-butyl alcohol

(±)-cis-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid

dicyclohexylcarbodiimide

→

(±)-cis-1,1-dimethylethyl 6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetate

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Temperatureto slowly warm to room temperature over a 76.5-hour period
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITcontinues five hours
4. 4
   Filtrationthe mixture filtered
5. 5
   WashThe precipitate is washed with diethyl ether
6. 6
   ConcentrationThe filtrate is concentrated to an oil
7. 7
   OtherThe crude product is chromatographed on silica gel eluting with 4:1 hexane
8. 8
   ConcentrationThe eluate is concentrated

Procedure

(±)-cis-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid (3.72 g, 17.44 mmol) is dissolved in 20 mL of dichloromethane, cooled to 0° C. and 0.2 g of 4-dimethylaminopyridine (DMAP) is added, followed by t-butyl alcohol and followed by 4.32 g of dicyclohexylcarbodiimide (DCC). This solution is allowed to slowly warm to room temperature over a 76.5-hour period. Thin layer chromotography (TLC) shows mainly product, and some slightly lower Rf by-products. The mixture is stirred one hour and 50 mL of dichloromethane is added and stirring continues five hours. An additional 100 mL of diethyl ether is added and the mixture filtered. The precipitate is washed with diethyl ether. The filtrate is concentrated to an oil. The crude product is chromatographed on silica gel eluting with 4:1 hexane:ethyl acetate. The eluate is concentrated to yield (±)-cis-1,1-dimethylethyl 6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetate.

Source