tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-(3,3-difluoroazetidin-1-yl)piperidine-1-carboxylate

HRID 1922699Notes

Reaction equation

HRID 1922699 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:16][C:17]1([F:21])[CH2:20][NH:19][CH2:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:19]2[CH2:20][C:17]([F:21])([F:16])[CH2:18]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 59606191tert-Butyl 4-(3,3-difluoroazetidin-1-yl)piperidine-1-carboxylateYield 959%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A 10 mL round-bottomed flask was charged with a solution of 4-oxopiperidine-1-carboxylic acid tert-butyl ester (0.4 g, 0.20 mmol), 3,3-difluoroazetidine hydrochloride (0.31 g, 0.24 mmol) and 4 Å molecular sieves (2.4 g) in DCE (10 mL). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.85 g, 4.01 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo to give 4-(3,3-Difluoroazetidin-1-yl)piperidine-1-carboxylic acid tert-butyl ester as a colourless oil (0.53 g, 96%). 1H NMR (300 MHz, CDCl3): δ 3.94-3.90 (m, 2H), 3.57 (t, J=11.9 Hz, 4H), 2.96-2.81 (m, 2H), 2.34-2.23 (m, 1H), 1.71-1.58 (m, 2H), 1.45 (s, 9H), 1.35-1.21 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-0693e8d90d3141d6aa700ff59666ce0f
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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