Formic Acid → 2-Chloro-6-formylaminomethylnicotinic acid methyl ester

HRID 2076158Notes

Reaction equation

HRID 2076158 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11](C=O)[CH:12]=[O:13])=[N:6][C:5]=1[Cl:16].O.C(O)=O>CO>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][CH:12]=[O:13])=[N:6][C:5]=1[Cl:16]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 962WaterHCID 583245322-Chloro-6-diformylaminomethylnicotinic acid methyl ester

Product 1

HCID 583245442-Chloro-6-formylaminomethylnicotinic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-chloro-6-diformylaminomethylnicotinic acid methyl ester (90.2 g, 0.352 mol) in methanol (530 mL) was added water (8 mL, 0.44 mol) and formic acid (27.6 mL, 0.73 mol) before the reaction mixture was heated at gentle reflux for 16 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in ethyl acetate (400 mL). The resultant solution was washed with water (400 mL) and the aqueous layer extracted with ethyl acetate (2×200 mL). The combined organic extracts were washed with brine (300 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound as an orange oil which solidified on standing (79.78 g, 99%). 1H NMR (CDCl3, 400 MHz) 8.34 (1H, s), 8.17 (1H, d, J=8.0 Hz), 7.31 (1H, d, J=7.8 Hz), 6.63 (1H, br s), 4.63 (2H, d, J=5.6 Hz), 3.96 (3H, s).

Workup

  1. temperaturewas heated
  2. temperatureat gentle reflux for 16 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionthe residue dissolved in ethyl acetate (400 mL)
  5. washThe resultant solution was washed with water (400 mL)
  6. extractionthe aqueous layer extracted with ethyl acetate (2×200 mL)
  7. washThe combined organic extracts were washed with brine (300 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6b3246620f23455a9529d42928eca27b
Source dataset
uspto-grants-2011_04
Patent number
US07923456B2

Reaction notes

Loading…