Hydrochloric Acid → 2-Chloro-6-(hydroxymethyl)-3-pyridinol

温度

90 °C

2-Chloro-3-pyridinol (20.0 g, 0.154 mole), NaHCO3 (19.5 g, 0.232 mole, 1.5 equ), and 150 mL of water are placed in a flask. The flask is placed in an oil bath at 90° C., and after 5 min, 37% aqueous formaldehyde (40.5 mL, 0.541 mole, 3.5 equ) is added in six unequal doses in the following order: 12 mL, 3×8 mL, then 2.2 mL all at 90-minute intervals and then the final 2.3 mL after the reaction had stirred for 15 h at 90° C. The reaction is stirred at 90° C. for another 4 h and then is cooled by placing the flask in an ice bath. The pH of the reaction is then adjusted to 1 using 6N HCl. The reaction is stirred for 1.5 h in an ice bath allowing an undesired solid to form. The undesired solid is removed by filtration, and the filtrate is extracted seven times with EtOAc. The combined organic extracts are concentrated in vacuo, toluene is added to the flask and removed in vacuo to azeotrope water, and then CH2Cl2 is added and removed in vacuo to obtain 2-chloro-6-(hydroxymethyl)-3-pyridinol (C1) as a pale yellow solid (81% yield) sufficiently pure for subsequent reaction. MS (EI) for C6H6ClNO2, m/z: 159(M)+.

1. customThe flask is placed in an oil bath at 90° C.
2. wait12 mL, 3×8 mL, then 2.2 mL all at 90-minute intervals
3. stirringThe reaction is stirred at 90° C. for another 4 h
4. temperatureis cooled
5. stirringThe reaction is stirred for 1.5 h in an ice bath
6. customto form
7. customThe undesired solid is removed by filtration
8. extractionthe filtrate is extracted seven times with EtOAc
9. concentrationThe combined organic extracts are concentrated in vacuo, toluene
10. additionis added to the flask
11. customremoved in vacuo
12. additionCH2Cl2 is added
13. customremoved in vacuo

ORDレコード

ord-58ac9de7634848a396a727da3ba27142

出典データセット

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07067515B2