Aluminium lithium hydride → HCID 68711441, compound

At −78° C., (2S)-methyl 2-amino-3-(tetrahydro-2H-pyran-2-yl)propanoate (1.84 g, 7.74 mmol) in THF (16 mL) was treated with lithium aluminum hydride (8 mL, 1 M in THF) at a rate such that the temperature remained below −65° C. The reaction was allowed to warm to rt. Upon completion, the reaction was cooled to 0° C. and quenched by dropwise addition of water, avoiding a rise in temperature above 2° C., the slurry was then stirred for an additional 1 h. The emulsion was dispersed by stirring with 1 M aq NaOH for 30 min, allowing warming to rt. Celite was added and stirred. The slurry was filtered through celite and washed several times with diethyl ether. The filtrate was concentrated to provide (2S)-2-amino-3-(tetrahydro-2H-pyran-2-yl)propan-1-ol as an oil and used without any further purification. A solution of (2S)-2-amino-3-(tetrahydro-2H-pyran-2-yl)propan-1-ol in THF (20 mL) and water (20 mL) was cooled to 0° C. Potassium carbonate (3.2 g, 23.2 mmol) was added, followed by di-tert-butyl dicarbonate (2.2 g, 10.06 mmol). The reaction was subsequently warmed to rt and stirred for 2 h. The aqueous layer was extracted 3 times with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, and filtered. After solvent removal the crude material was purified by chromatography on silica gel (EtOAc/Hex) to afford tert-butyl (2S)-1-hydroxy-3-(tetrahydro-2H-pyran-2-yl)propan-2-ylcarbamate (1.41 g) as an oil. MS m/z 282 (M+Na).

1. customremained below −65° C
2. temperatureUpon completion, the reaction was cooled to 0° C.
3. customquenched by dropwise addition of water
4. customin temperature above 2° C.
5. additionThe emulsion was dispersed
6. stirringby stirring with 1 M aq NaOH for 30 min
7. temperatureallowing warming to rt
8. additionCelite was added
9. stirringstirred
10. filtrationThe slurry was filtered through celite
11. washwashed several times with diethyl ether
12. concentrationThe filtrate was concentrated

ORD record

ord-8330c6e6f24a4a65a6433696c8cf4449

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487108B2