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

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%).

1. customThe reaction was quenched with a few drops of water
2. additiondiluted with diethyl ether (50 mL) and tetrahydrofuran (25 mL)
3. additionThe reaction mixture was basified to a pH of ˜11 by the addition of potassium hydroxide pellets
4. stirringstirred vigorously for 30 minutes
5. filtrationThe reaction mixture was filtered over sodium sulfate
6. concentrationconcentrated in vacuo
7. dissolutionredissolved in methylene chloride (10 mL)
8. dry with materialdried once more over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto afford a yellow crystalline solid, which
12. customwas used in the next step without any further purification (400 mg, 100%)

ORD record

ord-8c2b4dbc37494cfb83c23da8bfe60101

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440976B2