反应详情

2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluorophenyl)morpholine TsOH salt (609 g, 1 mol) and 4-N,N-dimethylaminomethyl-5-formyl-1,2,3-triazole (225 g, 1.5 mol) are suspended in 3L of toluene and 1 L of DMF. The resulting suspension was stirred for 30 minutes, then 1 eq. of sodium triacetoxyborohydride (212 g, 1 mol) was added. After 30 minutes, another portion of sodium triacetoxyborohydride (212g, 1 mol) was added. The resulting solution/suspension was aged at 25° C. for 5 hours and the reaction was completed when starting material secondary amine was less than 0.1 A % (at 220 nm) as judged by LC. When the reaction was completed, 2 eq. of 1N HCl (2 L, 2 mol) was added and the reaction mixture was aged for 4 hours (to break some boron complexes). The solution was then neutralized back to pH=8~9 with NaOH or Na3PO4 and extracted with toluene (3 L) and organic layer was washed twice with water and concentrated to obtain 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)-ethoxy)-4-(5-(dimethylamino)-methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine.

1. waitAfter 30 minutes
2. waitThe resulting solution/suspension was aged at 25° C. for 5 hours
3. waitthe reaction mixture was aged for 4 hours
4. extractionextracted with toluene (3 L) and organic layer
5. washwas washed twice with water
6. concentrationconcentrated