Lithium aluminum hydride → (1R,3S,4S)-2-azabicyclo(2.2.1)heptan-3-ylmethanol

Participants

Reaction Steps

To a slurry of (1R,3S,4S)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid hydrogen chloride (500 mg, 3 mmol) in tetrahydrofuran (4.6 mL) was added lithium tetrahydroaluminate (1N solution in tetrahydrofuran, 5.7 mL, 6 mmol) dropwise over 10 minutes. The reaction mixture was stirred overnight at ambient temperature under an atmosphere of nitrogen. The reaction was quenched with a few drops of water, diluted with diethyl ether (50 mL) and tetrahydrofuran (25 mL). The reaction mixture was basified to a pH of ˜11 by the addition of potassium hydroxide pellets and then stirred vigorously for 30 minutes. The reaction mixture was filtered over sodium sulfate, concentrated in vacuo, redissolved in methylene chloride (10 mL), dried once more over sodium sulfate, filtered, and concentrated in vacuo to afford a yellow crystalline solid, which was used in the next step without any further purification (400 mg, 100%).

Provenance & Evidence