Ammonia → 2-Chloro-3-methylpyridine-4-carbonitrile

Temperature

0 °C

2-Chloro-3-methyl-4-pyridinecarboxylic acid (30 g; 174 mmol) was dissolved in pyridine (250 ml) and cooled to 0° C. Methanesulfonyl chloride (13.6 ml) was then added dropwise and the reaction mixture was stirred at 0° C. for 1 hour. NH3 (gas) was added under pressure and the reaction mixture was stirred at room temperature for 1 h. After the reaction had reached completion, the excess NH3 was removed in vacuo. The reaction mixture was then cooled to 0° C., methanesulfonyl chloride (140 ml) was added and the reaction mixture stirred at room temperature overnight. The mixture was then poured into 0.1 M HCl (200 ml) at 0° C. (with care), and adjusted to pH=7 with 1 M NaOH. The reaction mixture was extracted with EtOAc (2×100 ml), washed with brine, dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was purified by flash column chromatography over silica gel (Biotage flash purification system; gradient: EtOAc/heptane from 15/85 to 30/70). The product fractions were collected and the solvent was evaporated in vacuo. Yield: 12.6 g of D1.

1. stirringthe reaction mixture was stirred at room temperature for 1 h
2. customthe excess NH3 was removed in vacuo
3. temperatureThe reaction mixture was then cooled to 0° C.
4. additionmethanesulfonyl chloride (140 ml) was added
5. stirringthe reaction mixture stirred at room temperature overnight
6. additionThe mixture was then poured into 0.1 M HCl (200 ml) at 0° C. (with care)
7. extractionThe reaction mixture was extracted with EtOAc (2×100 ml)
8. washwashed with brine
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. customthe solvent evaporated in vacuo
12. customThe residue was purified by flash column chromatography over silica gel (Biotage flash purification system; gradient: EtOAc/heptane from 15/85 to 30/70)
13. customThe product fractions were collected
14. customthe solvent was evaporated in vacuo

ORD record

ord-8093eb9a64c14692b792f3bf2999db84

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08779158B2