Sodium Bicarbonate → N-(4-chloro-3-hydroxymethyl-phenyl)-2-methyl-6-trifluoromethyl-nicotinamide

HRID 1919606Notes

Reaction equation

HRID 1919606 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([NH:10][C:11]([C:13]2[C:14]([CH3:23])=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=2)=[O:12])[CH:7]=[CH:6][C:5]=1[Cl:24].[BH4-].[Li+].C(=O)(O)[O-].[Na+]>O1CCCC1>[Cl:24][C:5]1[CH:6]=[CH:7][C:8]([NH:10][C:11](=[O:12])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[N:15][C:14]=2[CH3:23])=[CH:9][C:4]=1[CH2:3][OH:2]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 323079312-Chloro-5-[(2-methyl-6-trifluoromethyl-pyridine-3-carbonyl)-amino]-benzoic acid methyl ester

Product 1

HCID 59515636N-(4-chloro-3-hydroxymethyl-phenyl)-2-methyl-6-trifluoromethyl-nicotinamideYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-chloro-5-[(2-methyl-6-trifluoromethyl-pyridine-3-carbonyl)-amino]-benzoic acid methyl ester (6.68 g; 18 mmol) in tetrahydrofuran (100 ml) was cooled to 0° C. Lithium borohydride (0.98 g; 45 mmol) was added portionwise and the reaction mixture allowed to warm to room temperature, followed by heating at 45° C. for 4 hours. The reaction was allowed to cool to room temperature and saturated sodium bicarbonate solution (100 ml) was added. This was extracted with ethyl acetate (3×50 ml). The organic layers were dried (magnesium sulphate), filtered and evaporated. The residue was purified by column chromatography (50% ethyl acetate in heptane) to give N-(4-chloro-3-hydroxymethyl-phenyl)-2-methyl-6-trifluoromethyl-nicotinamide (3.29 g, 54%).

Workup

  1. temperatureby heating at 45° C. for 4 hours
  2. temperatureto cool to room temperature
  3. extractionThis was extracted with ethyl acetate (3×50 ml)
  4. dry with materialThe organic layers were dried (magnesium sulphate)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography (50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a2b882dfe27e43c4864cad9b428e40fa
Source dataset
uspto-grants-2012_05
Patent number
US08168653B2

Reaction notes

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