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 (150 g, 0.22 mol, from Example 2) and 2.25 L of isopropyl acetate. The suspension was stirred while 0.525 L 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 (300 mL) and water (300 mL). Five normal HCl (180 mL) was added and the reaction was stirred until all (R)-tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate was consumed. The two layers were separated. The pH of the aqueous layer was adjusted to >12 with 225 mL of 5N sodium hydroxide. The cloudy mixture was extracted with two portions of dichloromethane (2.25 L and 1.13 L). The solution was aged for 3 days for crystallization. (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine was isolated by filtration as a off-white crystalline solid (700 mg).