Phosphorus oxychloride → 6-CHLORO-5-NITRONICOTINIC ACID

Temperature

105 °C

A suspension of 6-hydroxy-5-nitronicotinic acid (8 g, 43.5 mmol) (prepared by literature nitration of 6-hydroxynicotinic acid) in phosphorus oxychloride (24.3 mL, 261.0 mmol) was heated to reflux (105° C.) for 3 h under a nitrogen atmosphere. At the end of this time period all of the solids had dissolved. The reaction was cooled to rt and poured over 500 mL crushed ice, and stirring was continued for 30 minutes until all of the ice had melted. The aqueous mixture was extracted with a 1:2 mixture of THF in diethyl ether (3×150 mL). The pooled organic extracts were washed with brine (1×), dried (MgSO4), and concentrated on a rotary evaporator to afford intermediate 56 as a light brown solid (8.37 g, 95%). ESI-MS m/e 405.3 (2M−1).

1. temperaturewas heated
2. dissolutionAt the end of this time period all of the solids had dissolved
3. temperatureThe reaction was cooled to rt
4. additionpoured over 500 mL
5. customcrushed ice
6. extractionThe aqueous mixture was extracted with a 1:2 mixture of THF in diethyl ether (3×150 mL)
7. washThe pooled organic extracts were washed with brine (1×)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated on a rotary evaporator

ORD record

ord-ec3793ece9c84de2a742898b2a7e34a1

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06803374B2