Sodium hydride → 5-Chloro-6-cyclopropylmethoxy-pyridine-2-carboxylic acid
Reaction equation
[H-].[Na+].[CH:3]1([CH2:6][OH:7])[CH2:5][CH2:4]1.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[N:13][C:14]=1Cl>>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[N:13][C:14]=1[O:7][CH2:6][CH:3]1[CH2:5][CH2:4]1Participants
4
Conditions
- Temperature
- 95 °C
Procedure
Sodium hydride (CAN 7646-69-7, 60% w/w, 1.05 g, 26 mmol) was added to cyclopropylmethanol (CAN 2516-33-8, 7.5 g) at 0° C. and the mixture was stirred for 1 h. 5,6-Dichloro-pyridine-2-carboxylic acid (1 g, 5 mmol) was added and the mixture was heated to 95° C. for 3 h. The solvent was removed under reduced pressure. The residue was diluted with water (10 mL) and adjusted to pH=3.0 by hydrochloric acid (3 N). The solution was extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with water (3×30 mL) and brine (2×40 mL) and evaporated to dryness to give the crude product (0.35 g, 25%), which was used in the next step without further purification, MS (EI): m/e=228.1 [M+H]+.