Water → Methyl 5-((4-formyl-6-methoxypyridin-3-yloxy)methyl)nicotinate

HRID 1471687Notes

Reaction equation

HRID 1471687 reaction equation
[OH:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5]([O:10][CH3:11])=[N:4][CH:3]=1.Cl.Cl[CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([CH:24]=1)[C:20]([O:22][CH3:23])=[O:21].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH:8]([C:7]1[CH:6]=[C:5]([O:10][CH3:11])[N:4]=[CH:3][C:2]=1[O:1][CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([CH:24]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:9]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 71627090Methyl 5-(chloromethyl)pyridine-3-carboxylate hydrochlorideHCID 722124985-Hydroxy-2-methoxyisonicotinaldehyde

Product 1

HCID 86690739Methyl 5-((4-formyl-6-methoxypyridin-3-yloxy)methyl)nicotinateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 5-hydroxy-2-methoxyisonicotinaldehyde (352 mg, 2.29 mmol, 1 eq.), methyl 5-(chloromethyl)nicotinate hydrochloride (506 mg, 2.29 mmol, 1 eq.), and K2CO3 (1.26 g, 9.16 mmol, 4 eq.) in DMF (8.0 mL) was heated at 60° C. for 3 h. The mixture was cooled and added into water (50 mL) dropwise. The precipitate was filtered, washed with water, and dried to give methyl 5-((4-formyl-6-methoxypyridin-3-yloxy)methyl)nicotinate (350 mg, 85%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.47 (s, 1H), 9.26 (d, J=2.0 Hz, 1H), 8.90 (d, J=2.2 Hz, 1H), 8.42 (t, J=2.1 Hz, 1H), 8.09 (s, 1H), 7.15 (s, 1H), 5.29 (s, 2H), 4.01 (s, 3H), 3.95 (s, 3H). LRMS (M+H+) m/z 303.1.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationThe precipitate was filtered
  3. washwashed with water
  4. customdried

Sources & evidence

ORD record
ord-7efc498172ae45c2b0cd24f767cdccba
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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