Dabco → HCID 54595836, compound

6-Bromo-1,4-dimethylindoline-2,3-dione and 4-bromo-1,6-dimethylindoline-2,3-dione. A solution of 1,4-diazabicyclo[2.2.2]octane (DABCO) (1.912 g, 17.05 mmol) in chloroform (5 mL) was cooled down to 0° C. under nitrogen gas and oxalyl chloride (1.492 mL, 17.05 mmol) was added dropwise, to form a pale yellow solid. To this solid was added slowly 3-bromo-N,N,5-trimethylaniline (0.73 g, 3.41 mmol) in chloroform (3 mL) at 0° C. The reaction mixture changed from a yellow suspension to a brown suspension. The reaction mixture was then warmed to room temperature, transferred into a sealed tube and heated to 90° C. for 3 h. The reaction mixture was neutralized with 10% sodium hydroxide solution to pH 8-9. The water layer was extracted with ethyl acetate (3×100 mL), washed with saturated ammonium chloride and brine, dried over magnesium sulfate, filtered and concentrated down to give the mixture of regioisomers as a red-brown solid. The regioisomers were separated by column chromatography (eluting with 0-100% ethyl acetate in hexane). The least polar compound was identified as 6-bromo-1,4-dimethylindoline-2,3-dione (0.34 g, 39.2%). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 7.27 (s, 1H), 7.21 (s, 1H), 3.12 (s, 3H), 2.44 (s, 3H). MS (ESI) m/z 256.1 [M+2]+. The regiochemistry was confirmed by NOE (NOE-NMR (400 MHz, DMSO-d6) δ (ppm) 2.44 (irradiated peak suppressed one major peak at 7.21 ppm). The most polar compound spot was identified as 4-bromo-1,6-dimethylindoline-2,3-dione and was further purified by trituration with methanol (0.146 g, 17%). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 7.16 (s, 1H), 7.02 (s, 1H), 3.11 (s, 3H), 2.38 (s, 3H). MS (ESI) m/z 256.1 [M+2]+. The regiochemistry was confirmed by nOE (NOE-NMR (400 MHz, DMSO-d6) δ (ppm) 2.38 (irradiated peak suppressed two major peaks at 7.02 and 7.16 ppm).

1. customto form a pale yellow solid
2. customtransferred into a sealed tube
3. temperatureheated to 90° C. for 3 h
4. extractionThe water layer was extracted with ethyl acetate (3×100 mL)
5. washwashed with saturated ammonium chloride and brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated down
9. customto give
10. additionthe mixture of regioisomers as a red-brown solid
11. customThe regioisomers were separated by column chromatography (eluting with 0-100% ethyl acetate in hexane)
12. customwas further purified by trituration with methanol (0.146 g, 17%)

ORD record

ord-b2f8a6a5b67345308681c0a12d034ddc

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299056B2