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

Temperatur

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-min intervals and then the final 2.3 mL after the reaction stirs for 15 h at 90° C. The reaction is stirred at 90° C. for another 4 h and then 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 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-min intervals
3. waitthe final 2.3 mL after the reaction stirs for 15 h at 90° C
4. temperaturecooled
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-Eintrag

ord-3f049d38af1f423db05847d643bf360e

Quelldatensatz

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06849620B2