反应详情

In a 50 L mechanically stirred vessel with Dean-Stark trap, toluene (22 L) was added to N-(3-methyl-6-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)acetamide (77) (1.04 kg, 4.50 mol). TosOH (84.0 g, 442 mmol) and ethylene glycol (750 mL, 13.4 mol) were added. The resulting mixture was heated to reflux overnight, cooled to rt, diluted with EtOAc (12 L) and washed with sat. aq. NaHCO3 (12 L) and sat. aq.s NaCl (12 L). The combined aq. washes were extracted with DCM (2×8 L). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel. The product containing fractions were combined and concentrated under reduced pressure to afford N-(3-methyl-5,7,8,9-tetrahydrospiro[benzo[7]annulene-6,2′-[1,3]dioxolan]-2-yl)acetamide (78) (900 g, 73% yield). 1H NMR (300 MHz, CDCl3): δ 7.45 (s, 1H), 7.03 (s, 1H), 6.92 (s, 1H), 3.96 (m, 4H), 3.02 (s, 2H), 2.76 (m, 2H), 2.20 (s, 3H), 2.18 (s, 3H), 1.98 (m, 2H), 1.74 (m, 2H).

1. temperatureThe resulting mixture was heated
2. temperatureto reflux overnight
3. washwashed with sat. aq. NaHCO3 (12 L) and sat. aq.s NaCl (12 L)
4. extractionThe combined aq. washes were extracted with DCM (2×8 L)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified on silica gel
9. additionThe product containing fractions
10. concentrationconcentrated under reduced pressure