3-Hydroxypyridine → 4-(3-Pyridyloxymethyl)2-phenylbenzoic acid methyl ester

To a mechanically-stirred 0° C. solution of 3-hydroxypyridine (4.4 g, 46 mmol) in DME (20 mL) was added potassium hexamethyldisilazide (0.5 M in toluene, 88.5 mL, 44 mmol) and the mixture was stirred for 15 minutes. 18-Crown-6 (1.46 g, 5.5 mmol) and a solution of 4-bromomethyl-2-phenylbenzoic acid methyl ester (6.8 g, 22 mmol) in toluene (25 mL) was added and the reaction mixture was vigorously stirred overnight. The reaction mixture was poured into 200 mL of water and the layers were separated. The aqueous phase was extracted with 2 portions of ethyl acetate and the combined organic phases were extracted with water and brine, dried (MgSO4), filtered and concentrated. The resulting oil was purified by flash chromatography (65% ethyl acetate-hexane) to give 4-(3-pyridyloxymethyl)-2-phenylbenzoic acid methyl ester (3.4 g).

1. waitthe reaction mixture was vigorously stirred overnight
2. customthe layers were separated
3. extractionThe aqueous phase was extracted with 2 portions of ethyl acetate
4. extractionthe combined organic phases were extracted with water and brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting oil was purified by flash chromatography (65% ethyl acetate-hexane)

ORD record

ord-46f1714deabd407f83f5d6ccbca48c2c

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06693123B2