Trifluoroacetic acid → (3R,4R)-4-(Azetidin-1-yl)piperidine-3-carboxamide

HRID 2066504Notes

Reaction equation

HRID 2066504 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:17][CH2:16][CH2:15]2)[CH:10]([C:18](=[O:20])[NH2:19])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:14]1([C@@H:11]2[CH2:12][CH2:13][NH:8][CH2:9][C@H:10]2[C:18]([NH2:19])=[O:20])[CH2:17][CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 668703584-Azetidin-1-yl-3-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 72208147(3R,4R)-4-(Azetidin-1-yl)piperidine-3-carboxamideYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-azetidin-1-yl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (0.66 g. 2.21 mmol) in anhydrous DMF (13 mL) was added formamide (370 μL, 9.32 mmol). The mixture was heated to 100° C. and a solution of sodium methoxide in MeOH (25 w/w. 330 μL, 1.44 mmol) was added with heating being continued for 2 h. The reaction mixture was cooled to RT, then 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-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester. To a solution of 4-azetidin-1-yl-3-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester in DCM (40 mL) was added TFA (5 mL) and the resulting mixture was stirred at RT for 1 h. 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 (280 mg, 69%).

Workup

  1. washwashed with MeOH
  2. washthen eluted with 2 M NH3 in MeOH
  3. customto give a 1:1 cis

Sources & evidence

ORD record
ord-e76067b0d7ba450cacabfc85f83f956b
Source dataset
uspto-grants-2012_10
Patent number
US08293735B2

Reaction notes

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