1,2-Dichloroethane → 4-(4-Chloro-2-fluorophenyl)nicotinamide

HRID 1398315Notes

Reaction equation

HRID 1398315 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14](O)=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1.C1C=CC2N(O)N=[N:24]C=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[Cl-].[NH4+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([NH2:24])=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 866959074-(4-Chloro-2-fluorophenyl)nicotinic acid

Product 1

HCID 867103214-(4-Chloro-2-fluorophenyl)nicotinamideYield 82.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (1.1 g, 4.37 mmol) (as prepared in Ex. 2, Part A) in anhydrous DMF (10 mL) cooled to 0° C. was added HOBT (1.339 g, 8.74 mmol), EDC (1.257 g, 6.56 mmol), DIEA (3.05 mL, 17.49 mmol) followed by ammonium chloride (1.169 g, 21.86 mmol). The reaction mixture was allowed to warm to RT and stirred for 12 h under a nitrogen atmosphere. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)nicotinamide (0.900 g, 3.59 mmol, 82% yield) LC/MS (ESI) m/e 251 [(M+H)+, calcd for C12H9ClFN2O 251]; LC/MS retention time (method A): tR=1.34 min.

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-01f8b8d6c8ca4e3b90df99383fd24f75
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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