Methanol → 3,5-Bis(benzyloxy)picolinic acid

Reaction equation

[CH2:1]([O:8][C:9]1[C:10]([C:23]#N)=[N:11][CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:25].[Na+].C[OH:28]>>[CH2:1]([O:8][C:9]1[C:10]([C:23]([OH:28])=[O:25])=[N:11][CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Reactant 3

HCID 887Methanol

HCID 14798Sodium Hydroxide

HCID 534879943,5-Bis(benzyloxy)picolinonitrile

Product 1

HCID 534879953,5-Bis(benzyloxy)picolinic acid

Procedure

To a solution of 3,5-bis-benzyloxy-pyridine-2-carbonitrile, 1, (26.0 g, 82.3 mmol) in MeOH (217 mL) is added 30% w/v sodium hydroxide (320 mL) and the reaction mixture is refluxed for 16 hours. The solvent is removed under reduced pressure and the resulting suspension is acidified with conc. HCl until the pH is between 1 and 2. The precipitate that results is collected by filtration, washed with H2O (10 mL) and dried overnight in a vacuum oven to afford 30 g (quantitative) of the desired product as the hydrochloride salt. 1H NMR (250 MHz, DMSO-d6) δ ppm 8.02 (1 H, d, J=2.4 Hz), 7.29-7.53 (11 H, m), 5.96 (1 H, br s), 5.28 (4 H, s). HPLC-MS: m/z 336 [M+H]+.