2-Chloro-5-nitropyridine → 2-(3,3-Difluoroazetidin-1-yl)-5-nitropyridine

HRID 2236166Notes

Reaction equation

HRID 2236166 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.Cl.[F:12][C:13]1([F:17])[CH2:16][NH:15][CH2:14]1.C(N(C(C)C)CC)(C)C>C1COCC1>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:15]2[CH2:16][C:13]([F:17])([F:12])[CH2:14]2)=[N:3][CH:4]=1)([O-:10])=[O:9]

Participants

5

Reactant 3

HCID 783082-Chloro-5-nitropyridineHCID 81531DiisopropylethylamineHCID 27582473,3-Difluoroazetidine hydrochloride

Product 1

HCID 529372622-(3,3-Difluoroazetidin-1-yl)-5-nitropyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

The 2-chloro-5-nitro-pyridine (317 mg, 2 mmol) and 3,3-difluoroazetidine hydrochloride (259 mg, 2 mmol) was mixed in 8 mL of THF. Diisopropylethylamine (1.4 mL) was added and the mixture was heated in a microwave at 120° C. for 20 minutes. After cooling to room temperature, the solid was filtered and the filtrate was distributed between ethyl acetate and water. The organic layers were evaporated and the solid material was triturated with methanol. The resulting solid was filtered to give 5-nitro-2-(3,3-difluoroazetidin-1-yl)pyridine. LCMS calcd for C8H7F2N3O2 m/e 215.16, obsd 216.1 (ES, M+H). Hydrogenation of the nitro compound, as above, provided 3-amino-6-(3,3-difluoroazetidin-1-yl)pyridine.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe solid was filtered
  3. customThe organic layers were evaporated
  4. customthe solid material was triturated with methanol
  5. filtrationThe resulting solid was filtered

Sources & evidence

ORD record
ord-c8aec9feb60e4993a7288baa9f8a0b52
Source dataset
uspto-grants-2010_05
Patent number
US07714126B2

Reaction notes

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