Hydrochloric Acid → methyl (1R,2R,3S,4S)-3-aminobicyclo[2.2.1]heptane-2-carboxylate hydrochloride

HRID 2408808Notes

Reaction equation

C(OC([NH:11][C@H:12]1[C@@H:17]2[CH2:18][C@@H:14]([CH:15]=[CH:16]2)[C@H:13]1[C:19]([O:21][CH3:22])=[O:20])=O)C1C=CC=CC=1.[ClH:23].O1CCOCC1>C(OCC)(=O)C.[Pd].C(OCC)C>[ClH:23].[NH2:11][C@H:12]1[C@@H:17]2[CH2:18][C@@H:14]([CH2:15][CH2:16]2)[C@H:13]1[C:19]([O:21][CH3:22])=[O:20]

Participants

Conditions

Temperature: 25 °C

Procedure

Methyl (1S,2R,3S,4R)-3-{[(benzyloxy)carbonyl]amino}bicyclo[2.2.1]hept-5-ene-2-carboxylate (5.5 g, 18.27 mmol) was dissolved in ethyl acetate (75 mL). 5% Palladium on carbon (650 mg) was added. The flask was degassed and backfilled with hydrogen gas via balloon. The mixture was stirred at 25° C. for 16 h. The mixture was passed through a plug of Celite and the filtrate was concentrated in vacuo to afford a thick clear oil. The oil was dissolved in ethyl acetate (15 mL) and added dropwise, with vigorous stirring, to a mixture of a 4.0 M solution of hydrochloric acid in 1,4-dioxane (10 mL, 40 mmol) in diethyl ether (90 mL). The desired product began to precipitate as a white solid. The mixture was stirred for 20 min. The precipitate was collected by vacuum filtration, and was washed with additional diethyl ether (15 mL). The solid was further dried in vacuo for 1 h to afford the desired product, methyl (1R,2R,3S,4S)-3-aminobicyclo[2.2.1]heptane-2-carboxylate hydrochloride (2.61 g, 12.69 mmol, 69%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.34-1.43 (4H, m), 1.54 (1H, d, J=9.5 Hz), 1.68 (1H, d, J=11.4 Hz), 2.47-2.48 (2H, m), 3.03 (1H, dd, J1=11.0 Hz, J2=4.0 Hz), 3.49-3.53 (1H, m), 3.62 (3H, s), 8.07 (3H, bs). LC-MS (ESI) calcd for C9H15NO2 (free amine) 169.11. found 170.1 [M+H+] (100%), 339.2 [2M+H+] (50%).

Workup

customThe flask was degassed
concentrationthe filtrate was concentrated in vacuo
customto afford a thick clear oil

Sources & evidence

ORD record: ord-1455f3603f9b4ece90dbf73158c649d4
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815847B2

Reaction notes

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