Trimethylsilyl cyanide → 1-(Aminomethyl)-4-(benzyloxymethyl)cyclohexanol

A suspension of EXAMPLE 341D (5 g), zinc iodide (0.183 g) and anhydrous ether (50 mL) was cooled in an ice bath and trimethylsilanecarbonitrile (3.45 mL) was added dropwise. The reaction was allowed to warm to ambient temperature with stirring continued 45 minutes. The reaction mixture was added via a syringe to a suspension of lithium aluminum hydride (2.78 g) in ether (75 mL) dropwise and the reaction mixture was then heated at reflux for 2 hours. The reaction was cooled in an ice bath and quenched very slowly by careful addition of water (2.8 mL), keeping the temperature below 5° C. Ether (100 mL) was added, followed by 4N aqueous sodium hydroxide (2.8 mL) and water (8.4 mL). The mixture was further diluted with ether (150 mL) and anhydrous sodium sulfate (70 g) was added. The resulting suspension was stirred for 18 hours and filtered. The solids were washed with ether (4×150 mL). The combined organics were dried with Na2SO4, filtered, and concentrated to provide the title compound.

1. temperaturethe reaction mixture was then heated
2. temperatureat reflux for 2 hours
3. temperatureThe reaction was cooled in an ice bath
4. customquenched very slowly by careful addition of water (2.8 mL)
5. customthe temperature below 5° C
6. additionEther (100 mL) was added
7. additionThe mixture was further diluted with ether (150 mL) and anhydrous sodium sulfate (70 g)
8. additionwas added
9. stirringThe resulting suspension was stirred for 18 hours
10. filtrationfiltered
11. washThe solids were washed with ether (4×150 mL)
12. dry with materialThe combined organics were dried with Na2SO4
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-7a008f33352b4831b0f1f18e00ddd0ab

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034875B2