Isopropyl Acetate → (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine
Reaction equation
C([C@](C(O)=O)(O)[C@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[CH:27]1[C:36]2[C:31](=[C:32]([NH:37][C@@H:38]3[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39]3)[CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][N:28]=1.C(OC(C)C)(=O)C>[OH-].[Na+]>[NH:40]1[CH2:41][CH2:42][C@@H:38]([NH:37][C:32]2[C:31]3[CH:30]=[CH:29][N:28]=[CH:27][C:36]=3[CH:35]=[CH:34][CH:33]=2)[CH2:39]1Participants
4
Procedure
To a 5 L flask equipped with a mechanical stirrer and an internal temperature probe were added (R)-tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate dibenzoyl-D-tartaric acid salt (180 g, 0.27 mol, from Example 2) and 2.7 L of isopropyl acetate. The suspension was stirred while 630 mL of 1N sodium hydroxide was added maintaining an internal reaction temperature below 30° C. Stirring was continued until a biphasic solution was obtained. The aqueous layer was removed and the remaining organic layer was washed with 1N sodium hydroxide (360 mL) and water (360 mL). Five normal HCl (215 mL) was added and the reaction was stirred until all (R)-tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate was consumed. The pH of the reaction was adjusted to >12 with 270 mL of 5N sodium hydroxide. The layers were separated. The pH of the aqueous layer was adjusted to >12 with 50 mL 5 N NaOH. The aqueous layer was re-extracted with 1.5 L of isopropyl acetate. The combined organic layers were concentrated to a volume of 770 mL.