Diisopropylamine → 1,1-Dimethylethyl 3-cyano-3-(hydroxymethyl)-1-azetidinecarboxylate

Temperatur

0 °C

To a solution of N-isopropylpropan-2-amine (11.54 mL) in THF (50 mL) was added dropwise a solution of n-butyllithium in hexane (1.6 M, 51.45 mL) at −78° C. The reaction mixture was warmed to 0° C. and then stirred for 30 minutes. The reaction mixture was cooled to −78° C. again, and then a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (5.0 g) in THF (30 mL) was added dropwise, followed by stirring at −78° C. for 1 hour. To the reaction mixture was added dropwise a solution of 1H-benzotriazol-1-yl-methanol (8.19 g) in THF (20 mL) at −78° C., followed by stirring at −78° C. for 3 hours. To the reaction mixture was added a saturated aqueous NH4Cl solution (100 mL), followed by extraction with EtOAc (50 mL) three times. The organic layer was washed with brine, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=100:0 to 50:50) to obtain tert-butyl 3-cyano-3-(hydroxymethyl)azetidine-1-carboxylate (5.68 g) as a white solid.

1. temperatureThe reaction mixture was cooled to −78° C. again
2. stirringby stirring at −78° C. for 1 hour
3. stirringby stirring at −78° C. for 3 hours
4. extractionfollowed by extraction with EtOAc (50 mL) three times
5. washThe organic layer was washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=100:0 to 50:50)

ORD-Eintrag

ord-84f85408e77d422ca94eca32bfe49fb5

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08193378B2