Diethyl Ether → {1-[(5-Cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester

Temperature

-78 °C

A solution of 2-cyclopropyl-[1,3,4]oxadiazole (2.16 g, 19.6 mmol) in dry THF (100 mL) is cooled to −78° C. nBuLi (1.6M in hexanes, 12.3 mL, 19.6 mmol) is added dropwise. The reaction mixture is stirred at −78° C. for 40 min. MgBr2.OEt2 (5.0692 g, 19.6 mmol) is added. The reaction mixture is allowed to warm up to −45° C. and stirred at that temperature for 1.5 hr. A solution of (1-formyl-propyl)-carbamic acid tert-butyl ester (3.7 g, 19.6 mmol) in THF (40 mL) is added. The reaction mixture is allowed to warm up to −20° C. and stirred at that temperature for 3.5 hrs. The reaction mixture is quenched with a solution of saturated NH4Cl solution and extracted with ethyl acetate. Combined organic extracts is washed with saturated NaCl solution and dried over MgSO4. The solvent is evaporated under reduced pressure and the crude is purified by column chromatography eluting with ethyl acetate and heptane mixture to give {1-[(5-cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester (2.83 g, 49%).

1. additionis added dropwise
2. temperatureto warm up to −45° C.
3. stirringstirred at that temperature for 1.5 hr
4. temperatureto warm up to −20° C.
5. stirringstirred at that temperature for 3.5 hrs
6. customThe reaction mixture is quenched with a solution of saturated NH4Cl solution
7. extractionextracted with ethyl acetate
8. washCombined organic extracts is washed with saturated NaCl solution
9. dry with materialdried over MgSO4
10. customThe solvent is evaporated under reduced pressure
11. customthe crude is purified by column chromatography
12. washeluting with ethyl acetate and heptane mixture

ORD record

ord-93a97c3767c244b9addf2079da96a648

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482448B2