Azetidine → tert-Butyl 4-(azetidin-1-yl)piperidine-1-carboxylate

To a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.75 g, 8.88 mmol) in dichloroethane (80 mL) was added azetidine (0.6 g, 10.53 mmol) and the mixture was stirred at RT for 30 min. Sodium triacetoxyborohydride (3.9 g, 18.44 mmol) was added and the resulting solution was stirred at RT for 18 h. The reaction mixture was partitioned between water and DCM and the layers separated. The organic layer was extracted further with DCM and the combined aqueous layers were concentrated in vacuo. The resultant white semi-solid was suspended in DCM and a saturated aqueous solution of NaHCO3 was added. The layers were thoroughly mixed, the organic layer isolated and the aqueous layer further extracted with DCM. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 4-azetidin-1-yl-piperidine-1-carboxylic acid tert-butyl ester as a white solid (2.0 g, 95%). BOC-deprotection of 4-azetidin-1-yl-piperidine-1-carboxylic acid tert-butyl ester (400 mg, 1.67 mmol) using TFA:DCM (1:4) gave the title compound as a yellow oil (185 mg, 79%)

1. stirringthe resulting solution was stirred at RT for 18 h
2. customThe reaction mixture was partitioned between water and DCM
3. customthe layers separated
4. extractionThe organic layer was extracted further with DCM
5. concentrationthe combined aqueous layers were concentrated in vacuo
6. additiona saturated aqueous solution of NaHCO3 was added
7. additionThe layers were thoroughly mixed
8. customthe organic layer isolated
9. extractionthe aqueous layer further extracted with DCM
10. washThe combined organic layers were washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated in vacuo

ORD record

ord-0c5ef37c7d094fc195ca6e03fb106ac7

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293735B2