Ammonium Chloride → 2-Chloro-5-fluoropyridine-3-carboxamide

HRID 2100509Notes

Reaction equation

HRID 2100509 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4](O)=[O:5].C1C=CC2N(O)N=[N:18]C=2C=1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[Cl-].[NH4+].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([NH2:18])=[O:5]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 114352432-Chloro-5-fluoronicotinic acid

Product 1

HCID 126297962-Chloro-5-fluoropyridine-3-carboxamideYield 43%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 2-chloro-5-fluoro-nicotinic acid (2.0 g, 11.39 mmol), HOBt (2.31 g, 17.13 mmol), BOP—Cl (4.37 g, 17.15 mmol), ammonium chloride (1.22 g, 22.86 mmol), DIPEA (12 ml, 66.74 mmol) in DMF (75 ml) was stirred at ambient temperature for 18 hours. The reaction mixture was diluted with EtOAc and washed with water and brine. The organic phases were dried over MgSO4, filtrated and evaporated. The crude product was purified by column chromatography (silica gel, EtOAc) to obtain 2-chloro-5-fluoro-nicotinamide (850 mg, 4.9 mmol; 43%) as white solid. MS (m/e): 175.1 [M+H+].

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic phases were dried over MgSO4
  3. filtrationfiltrated
  4. customevaporated
  5. customThe crude product was purified by column chromatography (silica gel, EtOAc)

Sources & evidence

ORD record
ord-b012ea65ae624ddcbdaa3a8b14257519
Source dataset
uspto-grants-2009_08
Patent number
US07572801B2

Reaction notes

Loading…