p-Toluenesulfonic acid → HCID 26370225, compound

Temperature

90 °C

To a solution of ethyl 6-amino-5-bromonicotinate (5.0 g, 20.4 mmol) in N,N-dimethylformamide (204 mL) were added bromoacetaldehyde dimethylacetal (3.45 g, 20.4 mmol) and p-toluenesulfonic acid (0.53 g, 3.1 mmol). The mixture was heated to 90° C. After 18 h, additional bromoacetaldehyde dimethylacetal (3.45 g, 20.4 mmol) and 4A° molecular sieves were added. The mixture was stirred at 90° C. for another 24 h. The mixture was warmed to ambient temperature and aqueous LiCl (3.0 M) was added. The mixture was extracted with ethyl acetate (3×). The combined organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. There was still some DMF in the crude product. Water was added and the mixture was extracted with t-butyl methyl ether, washed with brine, dried over sodium sulfate, filtered and concentrated. The mixture was carried on to the next step: LC-MS [M]=269.0.

1. temperatureThe mixture was warmed to ambient temperature
2. extractionThe mixture was extracted with ethyl acetate (3×)
3. washThe combined organic layer was washed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. additionWater was added
8. extractionthe mixture was extracted with t-butyl methyl ether
9. washwashed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-6e8cc01a0e554696bbc44e98e6fa6677

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238647B2