The general procedure for the synthesis of 5-hydrazino-2-methoxypyridine hydrochloride from 5-amino-2-methoxypyridine is as follows:
1. Dissolve sodium nitrite (3.795 g) in water (20 ml) to prepare a solution.
2. the above solution was added slowly dropwise to a concentrated hydrochloric acid solution of 5-amino-2-methoxypyridine (6.21 g) while cooling in an ice bath.
3. Hydrochloric acid (50 ml) was added slowly over a period of 60 minutes and the reaction mixture was continued to be stirred at the same temperature for 30 minutes.
4. A concentrated hydrochloric acid solution of tin(II) chloride dihydrate (39.5 g) was prepared.
5. Hydrochloric acid (30 ml) was added dropwise over a period of 30 minutes at an internal temperature of about 10°C in the reaction solution, followed by stirring of the reaction mixture for 2 hours at room temperature.
6. Phase separation was carried out by adding aqueous (300 ml) solution of sodium hydroxide (75 g) and diethyl ether to the reaction solution under cooling in an ice bath.
7. The aqueous phase was extracted twice with diethyl ether, after which the aqueous phase was saturated with sodium chloride and again extracted with diethyl ether.
8. All organic phases were combined and dried with anhydrous sodium sulfate.
9. After filtration, an ethanolic solution of 1 M hydrochloric acid (50 ml) was added to the filtrate and the mixture was stirred.
10. The solid precipitate formed was collected by filtration, washed with diethyl ether and dried to give the target product 5-hydrazino-2-methoxypyridine hydrochloride (5.02 g, 57% yield).
Product characterization data:
1H-NMR (400 MHz, DMSO-d6) δ: 3.81 (3H, s), 6.82 (1H, d, J = 8.8 Hz), 7.57 (1H, dd, J = 8.8, 2.9 Hz), 7.97 (1H, d, J = 2.9 Hz), 8.55-9.20 (1H, br), 10.13-10.50 (3H, br).
MS (ESI) m/z: 140 (M + H)+.
