3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → [1,3′-Biazetidine]-1′-carboxylic acid, 3,3-difluoro-, 1,1-dimethylethyl ester

HRID 1945547Notes

Reaction equation

HRID 1945547 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:14][C:15]1([F:19])[CH2:18][NH:17][CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:17]2[CH2:18][C:15]([F:19])([F:14])[CH2:16]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 59606024[1,3′-Biazetidine]-1′-carboxylic acid, 3,3-difluoro-, 1,1-dimethylethyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A 25 mL round-bottomed flask was charged with a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (0.4 g, 2.34 mmol), 3,3-difluoroazetidine hydrochloride (0.364 g, 2.80 mmol) and 4 Å molecular sieves (2.43 g) in DCE (10 mL). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.99 g, 4.67 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. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give the title compound as a colourless oil (0.33 g, 57%). 1H NMR (300 MHz, CDCl3): δ 4.02-3.69 (m, 4 H), 3.65 (t, J=12.15 Hz, 4 H), 3.55-3.48 (m, 1 H), 1.43 (s, 9 H).

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
  4. customThe residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-3c1f075624d14042aeb8b3da90a85360
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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