Methanol → 6-Chloro-N-[(3-Fluorophenyl)-methyl]-2-methoxy-4-methyl-pyridine-3-carboxylic acid amide

HRID 1753869Notes

Reaction equation

HRID 1753869 reaction equation
[H-].[Na+].Cl[C:4]1[C:9]([C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[O:11])=[C:8]([CH3:21])[CH:7]=[C:6]([Cl:22])[N:5]=1.[OH2:23].[CH3:24]O>>[Cl:22][C:6]1[N:5]=[C:4]([O:23][CH3:24])[C:9]([C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[O:11])=[C:8]([CH3:21])[CH:7]=1

Participants

5

Reactant 4

HCID 887Methanol2×HCID 962WaterHCID 24758Sodium hydrideHCID 866643132,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide

Product 1

HCID 866643196-Chloro-N-[(3-Fluorophenyl)-methyl]-2-methoxy-4-methyl-pyridine-3-carboxylic acid amideYield 54%

Conditions

Temperature
70 °C

Procedure

330 mg (8.3 mmol, 60% w/w in mineral oil) NaH were slowly added to Methanol (30 ml) at RT and stirring was continued at RT for 45 min. Then 2.35 g (7.5 mmol) 2,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide (synthesis is described in section a) of example 2) were added and the RM was heated to 70° C. for 24 h. After cooling to RT water (10 ml) was added and most of the MeOH was removed in vacuo. The mixture was then extracted with EtOAc and the organic layer was washed twice with brine, dried over MgSO4 and concentrated in vacuo. Crystallisation (hexane/EtOAc 3:1) of the residue yielded 1.24 g (0.4 mmol, 54%) 6-Chloro-N-[(3-Fluorophenyl)-methyl]-2-methoxy-4-methyl-pyridine-3-carboxylic acid amide.

Workup

  1. additionwere added
  2. customwas removed in vacuo
  3. extractionThe mixture was then extracted with EtOAc
  4. washthe organic layer was washed twice with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customCrystallisation (hexane/EtOAc 3:1) of the residue

Sources & evidence

ORD record
ord-0f4fdb93759a4b178fae655765b3d25f
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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