Hydrochloric Acid → (R)-(2-adamantyl) 3-(isobutoxycarbonylamino)pyrrolidine-1-carboxylate

HRID 1948703

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH:17]2[CH:24]3[CH2:25][CH:20]4[CH2:21][CH:22]([CH2:26][CH:18]2[CH2:19]4)[CH2:23]3)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27]I.[H-].[Na+].Cl>C1COCC1>[C:1]([O:5][C:6]([N:8]([CH3:27])[CH:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH:17]2[CH:18]3[CH2:19][CH:20]4[CH2:21][CH:22]([CH2:23][CH:24]2[CH2:25]4)[CH2:26]3)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3].[CH2:2]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH:17]2[CH:24]3[CH2:23][CH:22]4[CH2:21][CH:20]([CH2:19][CH:18]2[CH2:26]4)[CH2:25]3)=[O:15])[CH2:10]1)=[O:7])[CH:1]([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

2-adamantyl 3-(tert-butoxycarbonyl(methyl)amino)pyrrolidine-1-carboxylate was prepared as follows. A vial equipped with a flea stirbar was charged with (3R)-(2-adamantyl) 3-(tert-butoxycarbonylamino)pyrrolidine-1-carboxylate (105 mg, 0.29 mmol), methyl iodide (36 μL, 0.58 mmol) and dry THF (1 mL). 60% NaH in oil (14 mg, 0.58 mmol) was added and the mixture was stirred overnight under N2. The mixture was heated at 50° C. for 1 h, cooled and applied to a 10-mL ChemElut cartridge, prewetted with 5% aq HCl (6 mL), and eluted with ether (20 mL). The eluate was concentrated and the residue was purified by preparative HPLC to afford (R) 2-adamantyl 3-(tert-butoxycarbonyl(methyl)amino)pyrrolidine-1-carboxylate (32 mg, 29%).

Workup

customA vial equipped with a flea stirbar
temperaturecooled
washeluted with ether (20 mL)
concentrationThe eluate was concentrated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-afb6651fe34f4b81af52e0f2456f07ea
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399504B2

Linked notes

Loading…