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

HRID 426083Notes

Reaction equation

HRID 426083 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:19]([CH:23]([CH3:25])C)[CH:20](C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.N1CCC1>CN(C=O)C.C(Cl)Cl>[N:19]1([C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[O:16])[CH2:20][CH2:25][CH2:23]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 23658779tert-Butyl 4-[(azetidin-1-yl)carbonyl]piperidine-1-carboxylateYield 106.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid (0.40 g, 1.75 mmol) was dissolved in dry DMF (5 mL) and to the solution were added DIPEA (1.22 mL, 7.0 mmol), TBTU (0.67 g, 2.1 mmol) and azetidine (0.12 g, 2.1 mmol). The reaction mixture was stirred at RT for 12 h. The mixture was diluted with methylene chloride and then washed with an aqueous solution of HCl (2 M) and then with an aqueous solution of NaHCO3 (sat.). The phases were separated by means of a phase separator column and the solvent was removed by evaporation. There was obtained 0.50 g (100%) of tert-butyl 4-(azetidin-1-ylcarbonyl)piperidine-1-carboxylate as a crude solid. 1H NMR (500 MHz, CDCl3): 1.4-1.5 (s, 9H), 1.6-1.9 (m, 5H), 2.2-2.4 (m, 3H), 2.6-2.8 (m, 2H), 3.9-4.2 (m, 5H).

Workup

  1. washwashed with an aqueous solution of HCl (2 M)
  2. customThe phases were separated by means of a phase separator column
  3. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-184d37613b5044d58a5e7709fb514b39
Source dataset
uspto-grants-2012_01
Patent number
US08106208B2

Reaction notes

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