Reaction #1528422

Reaction equation

(Bromomethyl)cyclopropane

diisopropylamine

n-butyllithium

3-cyanoazetidine-1-carboxylic acid tert-butyl ester

→

product

Tert-butyl 3-cyano-3-(cyclopropylmethyl)azetidine-1-carboxylate

Solvents

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGthe solution stirred for 1 hour
2. 2
   workup.STIRRINGwith stirring
3. 3
   workup.STIRRINGthe solution stirred for 30 minutes at −78° C.
4. 4
   Temperatureto warm to ambient temperature
5. 5
   workup.STIRRINGstirred for 3 hours
6. 6
   TemperatureThe reaction was cooled in an ice bath
7. 7
   Otherquenched with saturated aqueous ammonium chloride
8. 8
   OtherThe solvent was evaporated
9. 9
   Otherthe residue was partitioned between EtOAc (300 ml) and water (100 ml)
10. 10
    OtherThe organic phase was separated
11. 11
    Dryingdried over MgSO4
12. 12
    Filtrationfiltered
13. 13
    Otherevaporated
14. 14
    Otherto give an orange oil
15. 15
    Washeluted with 15% EtOAc DCM

Procedure

To a solution of diisopropylamine (3.33 g 4.64 ml; 32.92 mmol) in THF (60 ml) at 0° C. was added n-butyllithium (2.5M in hexanes; 13.17 ml; 32.92 mmol). The solution was stirred for 30 minutes then cooled to −78° C. A solution of 3-cyanoazetidine-1-carboxylic acid tert-butyl ester (5 g; 27.43 mmol) in THF (40 ml) was added and the solution stirred for 1 hour. (Bromomethyl)cyclopropane (4.81 g 3.42 ml; 35.67 mmol) was then added dropwise with stirring and the solution stirred for 30 minutes at −78° C., then allowed to warm to ambient temperature, and stirred for 3 hours. The reaction was cooled in an ice bath and quenched with saturated aqueous ammonium chloride. The solvent was evaporated and the residue was partitioned between EtOAc (300 ml) and water (100 ml). The organic phase was separated, dried over MgSO4, filtered and evaporated to give an orange oil. The crude product was passed through a silica gel plug eluted with 15% EtOAc DCM to give the product as a pale yellow oil. (5.25 g)

Source