Dimethylformamide → Ethyl benzoate

Temperature

70 °C

(4-{[(2-Chloro-pyridine-3-carbonyl)-amino]-methyl}-benzyl)-carbamic acid tert-butyl ester (12.0 g, 32.2 mmol) (see Preparation 7), 3-hydroxy-benzoic acid ethyl ester (6.42 g, 38.6 mmol) and caesium carbonate (15.7 g, 48.3 mmol) were stirred in dioxan (180 ml) at 70° C. under an atmosphere of nitrogen for 18 hours. Starting material remained, so a further aliquot of 3-hydroxy-benzoic acid ethyl ester (6.42 g, 38.6 mmol) and caesium carbonate (15.7 g, 48.3 mmol) were added along with dioxan (420 ml) and N,N-dimethylformamide (40 ml) and the reaction stirred at 70° C. for a further 22 hours. The solvent was then removed under reduced pressure, the residue partitioned between ethyl acetate (200 ml) and water (200 ml), and the organic layer separated. The organic layer was then washed with a saturated aqueous solution of sodium chloride (3-fold 100 ml), the solvent removed in vacuo and the residue purified by flash column chromatography on silica gel eluting with a solvent gradient of 0:100 changing to 50:50, by volume, ethyl acetate:hexane to give 3-{3-[4-tert-butoxycarbonylamino-methyl)-benzylcarbamoyl]-pyridin-2-yloxy}-benzoic acid ethyl ester (7.42 mg) as an off-white foam.

1. customThe solvent was then removed under reduced pressure
2. customthe residue partitioned between ethyl acetate (200 ml) and water (200 ml)
3. customthe organic layer separated
4. washThe organic layer was then washed with a saturated aqueous solution of sodium chloride (3-fold 100 ml)
5. customthe solvent removed in vacuo
6. customthe residue purified by flash column chromatography on silica gel eluting with a solvent gradient of 0:100 changing to 50:50, by volume, ethyl acetate

ORD record

ord-7f7df79f628c4485a001f2dc3be63b75

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06756392B2