Ammonia → (R)-2-amino-1-((S)-2,5-dihydrofuran-2-yl)ethanol

Temperature

75 °C

Alternative preparation of Benzyl (R)-2-((S)-2,5-dihydrofuran-2-yl)-2-hydroxyethylcarbamate (18); Zinc and ‘One-Pot’ Procedure 2. A solution of ammonium chloride (4 g, 74.8 mmol) in water (50 mL) then zinc dust (4 g, 61.6 mmol) were added to a solution of bromotosylate (47) (20 g, 55 mmol) in tetrahydrofuran (200 mL) and propan-2-ol (100 mL). The mixture was stirred for 6 hours then zinc dust (4 g, 61.6 mmol) was added. The mixture was stirred for an additional 16 hours before filtering the suspension through celite in vacuo. The filter cake was washed with diethyl ether (400 mL). Hydrochloric acid (1M, 400 mL) was added to the filtrate then the organic phase separated. The aqueous layer was extracted with diethyl ether (400 mL) then the combined organic phase was washed with brine (400 mL), then dried (MgSO4), filtered and reduced in vacuo to leave a residue. The residue was partially dissolved in ammonium hydroxide (92 mL) and a solution of ammonia in 2-propanol (60 mL, 2.0M, 120 mmol) then divided into 6 equal portions and heated in sealed tubes at 75° C. for 16 hours. The mixtures were combined using methanol, then the solvents were removed in vacuo. The residue was azeotroped with diethyl ether (3×50 mL) to obtain (R)-2-amino-1-((S)-2,5-dihydrofuran-2-yl)ethanol which was used without further purification.

1. stirringThe mixture was stirred for an additional 16 hours
2. filtrationbefore filtering the suspension through celite in vacuo
3. washThe filter cake was washed with diethyl ether (400 mL)
4. additionHydrochloric acid (1M, 400 mL) was added to the filtrate
5. customthe organic phase separated
6. extractionThe aqueous layer was extracted with diethyl ether (400 mL)
7. washthe combined organic phase was washed with brine (400 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customto leave a residue
11. customthe solvents were removed in vacuo
12. customThe residue was azeotroped with diethyl ether (3×50 mL)

ORD record

ord-eb04dfe0c63142b98ca0e2ae1e6ceb77

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08039641B2