Water → 4-Azetidin-1-yl-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 2066505Notes

Reaction equation

C[O:2][C:3]([CH:5]1[CH:10]([N:11]2[CH2:14][CH2:13][CH2:12]2)[CH2:9][CH2:8][N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6]1)=O.[H-].C([Al+]CC(C)C)C(C)C.O>C(Cl)Cl>[C:18]([O:17][C:15]([N:7]1[CH2:8][CH2:9][CH:10]([N:11]2[CH2:12][CH2:13][CH2:14]2)[CH:5]([CH2:3][OH:2])[CH2:6]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of 4-azetidin-1-yl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (373 mg, 1.25 mmol) in anhydrous DCM (10 mL) was slowly added a solution of diisobutylaluminum hydride in hexanes (1M, 3.8 mL, 3.8 mmol) at −70° C. The reaction mixture was allowed to warm to −10° C. over 90 min, then stirred at RT for 15 min. Water was added to the reaction mixture before being loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give 4-azetidin-1-yl-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester. To a solution of 4-azetidin-1-yl-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester in DCM (10 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give a 1:1 cis:trans mixture of the title compound as a colourless oil (188 mg, 88%).

Workup

washThe cartridge was washed with MeOH
washthen eluted with 2 M NH3 in MeOH

Sources & evidence

ORD record: ord-e26b5466db324cdab10b807aa34e954e
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293735B2

Reaction notes

Loading…