Diisopropylamine → HCID 9883205, compound

Temperature

0 °C

To a solution of diisopropylamine (0.2 mL, 1.43 mmol) in THF (3 mL) at 0° C. was added n-butyllithium (0.9 mL of a 1.6 M solution in hexane, 1.44 mmol). After stirring at 0° C. for 10 minutes, the resulting lithium diisopropylamide solution was treated with a solution of N-benzyl-2-methylbenzamide (145 mg, 0.64 mmol) in THF (2 mL). The resulting deep purple solution was stirred at 0° C. for 75 minutes at which time it was treated with a solution of N-methoxy-N-methyl-benzamide (117 mg, 0.71 mmol) in THF (2 mL). After slowly warming to ambient temperature over 100 minutes the reaction was quenched by the addition of 3N HCl (12 mL). The biphasic mixture was then heated to reflux with vigorous stirring. After 1 hour at reflux the reaction mixture was allowed to cool to ambient temperature. After cooling, the reaction was diluted with ether (50 mL), and basified by careful addition of solid Na2CO3. The basic aqueous was extracted with ether (3×20 mL), combined organics were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under educed pressure to afford a pale orange oil. The crude product was purified by silica gel column chromatography eluting with a gradient from 0% to 20% ethyl acetate/hexane on a 20 g silica column. The product peak was collected to afford 2-benzyl-3-phenyl-2H-isoquinolin-1-one (22 mg, 11% yield) as a clear oil that slowly solidified to a white waxy solid. 1H-NMR (400 MHz, CDCl3): δ 8.49 (1H, d J=8.3 Hz), 7.68-7.63 (1H, m), 7.53-7.48 (2H, m), 7.42-7.37 (1H, m), 7.35-7.30 (2H, m), 7.22-7.14 (5H, m), 6.92-6.88 (2H, m), 6.45 (1H, s), 5.25 (2H, s) ppm.

1. stirringThe resulting deep purple solution was stirred at 0° C. for 75 minutes at which time it
2. temperatureAfter slowly warming to ambient temperature over 100 minutes the reaction
3. customwas quenched by the addition of 3N HCl (12 mL)
4. temperatureThe biphasic mixture was then heated
5. temperatureto reflux with vigorous stirring
6. temperatureAfter 1 hour at reflux the reaction mixture
7. temperatureto cool to ambient temperature
8. temperatureAfter cooling
9. additionthe reaction was diluted with ether (50 mL)
10. additionbasified by careful addition of solid Na2CO3
11. extractionThe basic aqueous was extracted with ether (3×20 mL)
12. washcombined organics were washed with brine (20 mL)
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under educed pressure
16. customto afford a pale orange oil
17. customThe crude product was purified by silica gel column chromatography
18. washeluting with a gradient from 0% to 20% ethyl acetate/hexane on a 20 g silica column
19. customThe product peak was collected

ORD record

ord-f8d44add1adc4fd5850e55037afe9910

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07265131B2