Methanol → rac-(1R,3R,4S)-2-[(tert-butoxy)carbonyl]-2-azabicyclo[2.2.1]heptane-3-carboxylic acid
Reaction equation
[C@@H:1]12[CH2:7][C@@H:4]([CH2:5][CH2:6]1)[C@@H:3]([C:8]([O:10]C)=[O:9])[N:2]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].CO.[OH-].[Li+]>C1COCC1>[C:15]([O:14][C:12]([N:2]1[C@H:3]([C:8]([OH:10])=[O:9])[C@H:4]2[CH2:7][C@@H:1]1[CH2:6][CH2:5]2)=[O:13])([CH3:18])([CH3:16])[CH3:17]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (1S,3S,4R)-2-tert-butyl 3-methyl 2-azabicyclo[2.2.1]heptane-2,3-dicarboxylate (1.67 g, 6.54 mmol) in THF:MeOH (41 mL:13 mL) was added aqueous Lithium hydroxide (1M, 8.2 mL, 8.2 mmol) and the reaction was allowed to stir at room temperature overnight. Upon completion, the reaction was concentrated in vacuo, diluted with ethyl acetate and washed with 1N HCl. The aqueous layer was back extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated to give (1S,3S,4R)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (1.36 g, 86%). 1H NMR (400 MHz, Methanol-d4) δ 6.43 (s, 1H), 5.84 (s, 1H), 5.74 (d, 1H), 4.34 (s, 1H), 3.36-3.18 (m, 3H), 3.17-3.06 (m, 3H), 3.02 (s, 3H), 2.97 (s, 6H).
Workup
- concentrationUpon completion, the reaction was concentrated in vacuo
- additiondiluted with ethyl acetate
- washwashed with 1N HCl
- extractionThe aqueous layer was back extracted with ethyl acetate
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-1a7858c626414b8783b9db1058dcc5db
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09156823B2
Reaction notes
Loading…