Sodium Hydroxide → 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]benzoic acid
Reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:23])[C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]#[C:15][C:16]2[CH:17]=[N:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[CH:8][CH:7]=1>CO>[Cl:22][C:19]1[N:18]=[CH:17][C:16]([C:15]#[C:14][C:13]#[C:12][C:9]2[CH:8]=[CH:7][C:6]([C:5]([OH:23])=[O:4])=[CH:11][CH:10]=2)=[CH:21][CH:20]=1Participants
4
Procedure
A 6M aq. solution of NaOH (15 ml) was added to a stirred solution of 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester. (9.06 g, 30 mmol) in MeOH (350 ml) at rt. The reaction solution was heated to reflux for 3 hours. The reaction stayed a mixture and did not turn clear. HPLC and LCMS indicated that the reaction was forming side products. The reaction was cooled to rt and some MeOH (˜200 ml) was removed by evaporation under reduced pressure. Water (400 ml) was added to the mixture. Conc. HCl was added dropwise to the stirred solution until acidic by pH paper (pH2). The yellow precipitate that formed was collected by suction filtration. The solid was washed with water (3×20 ml) and hexane (2×20 ml) to give the crude product. HPLC indicated that there was approximately 40% product in the mixture. The crude reaction product was purified by flash chromatography using EtOAc (8-10%)/hexane as eluant. The pure fractions were evaporated and dried in vacuo to give 4.2 g of product 3 in 50% yield.