Chloroacetyl chloride → 6-methoxy-4a,5,10,10a-tetrahydro-4H-naphto[2,3-b][1,41oxazin-3-one

Temperature

25 °C

To a solution of 3-amino-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-ol (1.7 g, 8.8 mmol) and triethylamine (1.5 ml, 11 mmol) in 100 ml of CH2Cl2 was added chloroacetyl chloride (1.0 g, 8.9 mmol) in 10 ml of CH2Cl2 dropwise at 0° C. The resulting solution was stirred for 1.5 h at 25° C. The reaction mixture was then diluted with EtOAc and washed with 1N aqueous HCl. Organic layer was dried over Na2SO4 and concentrated in vacuo, yielding an oil which corresponds to the amide. The oily residue was redissolved in 20 ml of THF, and NaH (0.35 g, 8.8 mmol) and tetrabutylammonium iodide (0.25 g, 0.67 mmol) were added into the solution at 0° C. The reaction mixture was stirred for 12 h at 25 ° C. It was diluted with EtOAc and washed with brine. The organic layer was dried over Na2SO4 and concentrated in vacuo, yielding an oily residue which was purified by column chromatography (50% CH2Cl2 -EtOAc) to provide 1.4 g (68%) of the desired product. 1H NMR (300 MHz, CDCl3): δ 2.45 (dd, 1H, J=10.5, 16.7 Hz), 2.85 (m, 1H), 3.11-3.34 (m, 2H), 3.65(m, 2H), 3.79 (s, 3H), 4.28 (AB q, 2H, 16.7 Hz), 6.68 (m, 2H), 7.07 (t, 1H, J=7.9 Hz).

1. washwashed with 1N aqueous HCl
2. dry with materialOrganic layer was dried over Na2SO4
3. concentrationconcentrated in vacuo
4. customyielding an oil which
5. stirringThe reaction mixture was stirred for 12 h at 25 ° C
6. washwashed with brine
7. dry with materialThe organic layer was dried over Na2SO4
8. concentrationconcentrated in vacuo
9. customyielding an oily residue which
10. customwas purified by column chromatography (50% CH2Cl2 -EtOAc)

ORD record

ord-74d5a1a691e2485fba3139270b87a8e5

Source dataset

uspto-grants-1997_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05610174