Dimethylformamide → 6-Chloro-5-nitro-1H-isochromen-1-one

Temperature

120 °C

A pressure tube was-charged with methyl 4-chloro-2-methyl-3-nitrobenzoate (13 g, 57 mmol) in N,N-dimethylformamide (10 mL, 200 mmol) was added 1,1-dimethoxy-N,N-dimethylmethanamine (26.5 mL, 200 mmol) and the reaction heated to 120° C. for 20 h. The solvents were removed and the resultant brown residue was redissolved in ethyl acetate (600 mL, 6000 mmol) and 130-270 mesh 60A silica gel (500 g, 6000 mmol) was added and the reaction stirred with a mechanical stirrer for 8 h. The silica gel was filtered off, washed with ethyl acetate (400 mL) and the organics were removed under vacuum and the residue purified by flash chromatography (330 g silica gel, 2-50% ethyl acetate/hexane) to obtain the two isomers in 14% yields each in almost 98% purity. MS m/z=226.2 (M+H). 1H NMR (400 MHz; DMSO) δ 8.35 (d, J=8.63 Hz, 1H), 7.95 (d, J=8.63 Hz, 1H), 7.76 (d, J=5.91 Hz, 1H), 6.61 (d, J=6.04 Hz, 1H).

1. customThe solvents were removed
2. filtrationThe silica gel was filtered off
3. washwashed with ethyl acetate (400 mL)
4. customthe organics were removed under vacuum
5. customthe residue purified by flash chromatography (330 g silica gel, 2-50% ethyl acetate/hexane)
6. customto obtain the two isomers in 14%
7. customyields each in almost 98% purity

ORD record

ord-4154922768b445298f273693c4f29b7e

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816371B2