Potassium Carbonate → tert-butyl 5,7-dichloro-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylate

4-[(3,5-Dichloro-2-iodo-benzoyl)-(4-methoxy-benzyl)-amino]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (9.0 g, 15 mmol) was dissolved in 100 mL of acetonitrile in a three flask fitted with a condenser and the mixture was sparged with N2 for 1 h. The flask was quickly opened and Pd(OAc)2 (336 mg, 1.5 mmol), PPh3 (786 mg, 3.0 mmol), K2CO3 (4.14 g, 30 mmol) and nBu4NBr (4.82 g, 15 mmol) was added. The mixture was heated to reflux overnight. After this time, the iodide was consumed and the mixture was cooled to rt and evaporated. The residue was taken up with EtOAc/H2O and the layers were separated. The organic layer was washed with brine, dried and concentrated to give the crude product. It was purified by column chromatography (PE:EtOAc=10:1) to give tert-butyl 5,7-dichloro-2-(4-methoxybenzyl)-3-oxo-2′,3′-dihydro-1′H-spiro[isoindoline-1,4′-pyridine]-1′-carboxylate (3.5 g, 48%). 1H NMR (CDCl3): 1.52 (s, 9H), 1.63 (s, 1H), 1.78 (m, 1H), 2.71 (m, 1H), 3.04 (m, 1H), 3.78 (s, 3H), 3.97 (m, 1H), 4.25 (m, 1H), 4.46 (m, 1H), 5.02 (m, 1H), 6.82 (m, 2H), 7.18 (m, 2H), 7.52 (s, 1H), 7.81 (s, 1H).

1. customfitted with a condenser
2. customthe mixture was sparged with N2 for 1 h
3. temperatureThe mixture was heated
4. temperatureto reflux overnight
5. customAfter this time, the iodide was consumed
6. customevaporated
7. customthe layers were separated
8. washThe organic layer was washed with brine
9. customdried
10. concentrationconcentrated
11. customto give the crude product
12. customIt was purified by column chromatography (PE:EtOAc=10:1)

ORD record

ord-960480494c0c44d4a03db1227b21edc6

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383629B2