4-(3-Methoxypropoxy)-3-methyl-2-pyridinemethanol

Take 100g HYDROXY rabeprazole (473.35mmol) was added to a 2L three-necked flask, followed by addition of 1L of tetrahydrofuran, 71.10g mercaptobenzimidazole (473.35mmol), 136.58g triphenylphosphine (520.69mmol).Open stirred and the temperature controlled at 0-10 .After added dropwise 90.678g (520.69mmol) azodicarboxylic acid diethyl ester.After completion of the dropwise addition, the reaction was kept 5h-10h, the reaction gusset fully monitored.After completion of the reaction, tetrahydrofuran was evaporated to dryness, then recrystallized from methanol to give 130.0 g of rabeprazole sulfide composition, yield 80%.50g 4-(3-methoxy-propoxy)-2, 3-dimethyl-pyridine N-oxide, 150ml acetic anhydride and 8 drops of concentrated sulfuric acid were put into a reaction flask and reacted at 90 Cfor 3 hours in oil bath. The acetic anhydride was vaporized under vacuum. 100ml water and 20g sodium hydroxide at ambient temperature were added to the flask and reacted at 50 C for 1 hour in water bath. And then the reaction solution was cooled, extracted by chloroform, dried, filtered and concentrated till dry. 200ml fresh chloroform and 30ml thionyl chloride were added to the residue and the reaction took place at ambient temperature for 5 hours and the reaction solution was concentrated under vacuum. After that, 400ml water was added to the residue and the pH value was adjusted to 8 with sodium carbonate solution. Finally, the expected product (brown semi-solid) was produced after the procedures of extracting the reaction solution by chloroform, drying and concentration.145 g (1.42 mol) of the acetic anhydride was added over 30 minutes to 150 g (0.71 mol) of 4-(3-methoxy propoxy)-2, 3-dimethyl pyridine-N-oxide at O0C. The solution was heated to 900C and stirred for 6 hrs. After the completion of reaction, it was distilled under reduced pressure to remove acetic anhydride. The obtained residue containing 2- (Reference Example 4) (Reference Example 3) 70 g of the 2-hydroxymethyl-4-(3-methoxy propoxy)-3 -methyl pyridine obtained in example 3 was dissolved in 135 ml of methylene dichloride to obtain a solution. 73.1 g (0.61 mol) of thionyl chloride was drop wise added to this solution at 0C. The obtained mixture was stirred at room temperature for 2 hrs. After the completion of reaction, the reaction mixture was distilled to remove the methylene dichloride & thionyl chloride under vacuum. The obtained residue was cooled to 5C and neutralized using saturated sodium bicarbonate solution to pH-7.5 and extracted with methylene dichloride. The methylene dichloride layer dried over sodium sulfate & filtered. The obtained filtrate concentrated to obtain 76 g (99 %) of 2-chloromethyl-4-(3-methoxy propoxy)-3-methyl pyridine as a brown oilSynthesis of 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine (Reference Example 1) (Reference Example 2) General procedure: To a solution of commercial 9a or 9b or 9c (3.56 mmol) in dichloromethane (20 mL) was added SOCl2 (2.8 mL). After 2 h stirring at room temperature, the reaction mixture was quenched with 2 M NaOH solution to pH 7-8. The solution was extracted several times with DCM, and the combined organic layers were washed saturated salt solution, dried over anhydrous MgSO4 and then evaporated in vacuo.50g 4-(3-methoxy-propoxy)-2, 3-dimethyl-pyridine N-oxide, 150ml acetic anhydride and 8 drops of concentrated sulfuric acid were put into a reaction flask and reacted at 90 Cfor 3 hours in oil bath. The acetic anhydride was vaporized under vacuum. 100ml water and 20g sodium hydroxide at ambient temperature were added to the flask and reacted at 50 C for 1 hour in water bath. And then the reaction solution was cooled, extracted by chloroform, dried, filtered and concentrated till dry. 200ml fresh chloroform and 30ml thionyl chloride were added to the residue and the reaction took place at ambient temperature for 5 hours and the reaction solution was concentrated under vacuum. After that, 400ml water was added to the residue and the pH value was adjusted to 8 with sodium carbonate solution. Finally, the expected product (brown semi-solid) was produced after the procedures of extracting the reaction solution by chloroform, drying and concentration.

Molecular Weight:211.26
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:6
Exact Mass:211.12084340
Monoisotopic Mass:211.12084340
Topological Polar Surface Area:51.6
Heavy Atom Count:15
Complexity:166
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes