Nitric Acid → 2-Methyl-4-nitro-pyridin-1-ol

Temperature

5 °C

2-Picoline-N-oxide (14)(21.9 g, 0.2 mmol) was added to a concentrated sulphuric acid (76 mL), maintaining the temperature below 40° C. The mixture was cooled to 5° C.; fuming nitric acid (60 mL) was the added dropwise over 15 minutes, maintaining reaction temperature below 10° C. After the addition was complete the reaction mixture was heated to 100° C. for 1.5 hours. The reaction was then cooled to rt and poured over ice (ca 500 g), the resultant green/yellow solution was neutralised by addition of sodium carbonate (ca 205 g over 1 hour). The mixture was then filtered and washed with water (2 L). The solid cake was then dissolved in DCM (500 mL) and dried over Na2SO4. Hexane (100 mL) was added to the DCM solution resulting in a yellow suspension which was filtered off and dried. Single peak in LC-MS analysis, (25.40 g 82.5%) no purification performed and taken through crude to next step.

1. temperaturemaintaining the temperature below 40° C
2. additionadded dropwise over 15 minutes
3. temperaturemaintaining
4. customreaction temperature below 10° C
5. additionAfter the addition
6. temperaturewas heated to 100° C. for 1.5 hours
7. temperatureThe reaction was then cooled to rt
8. filtrationThe mixture was then filtered
9. washwashed with water (2 L)
10. dissolutionThe solid cake was then dissolved in DCM (500 mL)
11. dry with materialdried over Na2SO4
12. additionHexane (100 mL) was added to the DCM solution
13. customresulting in a yellow suspension which
14. filtrationwas filtered off
15. customdried
16. customSingle peak in LC-MS analysis, (25.40 g 82.5%) no purification

ORD record

ord-5e8b5a8540274c019c027b10d113d965

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902193B2