Acetic Acid → 5-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane, (2S,3S,5S)-

Temperature

60 °C

To a stirred solution of (2S,3S,5S)-2-(N,N-dibenzylamino)-3-hydroxy-5-(t-butyloxycarbonylamino)-1,6-diphenylhexane (12 g, 21.3 mmol) in methanol (350 mL) was charged ammonium formate (8.05 g, 128 mmol, 6.0 eq) and 10% palladium on carbon (2.4 g). The solution was stirred under nitrogen at 60° C. for three hours and then at 75° C. for 12 hours. An additional amount of ammonium formate (6 g) and 10% palladium on carbon (1.5 g) was added as well as 1 mL of glacial acetic acid. The reaction was driven to completion within 2 hours at a reflux temperature. The reaction mixture was then cooled to room temperature and then filtered through a bed of celite. The filter cake was washed with methanol (75 mL) and the combined filtrates were concentrated under reduced pressure. The residue was taken up in 1N NaOH (300 mL) and extracted into methylene chloride (2×200 mL). The combined organic layers were washed with brine (250 mL) and dried over sodium sulfate. Concentration of the solution under reduced pressure provided the desired product as a light colored oil which slowly crystallized upon standing (5 g). Further purification of the product could be accomplished by flash chromatography (silica gel, 5% methanol in methylene chloride). 300 MHz 1H NMR (CDCl3) δ1.42 (s, 9H), 1.58 (m, 1H), 1.70 (m, 1H), 2.20 (s, broad, 2H), 2.52 (m, 1H), 2.76-2.95 (m, 4H), 3.50 (m, 1H), 3.95 (m, 1H), 4.80 (d, broad, 1H), 7.15-7.30 (m, 10H).

1. waitat 75° C. for 12 hours
2. waitThe reaction was driven to completion within 2 hours at a reflux temperature
3. temperatureThe reaction mixture was then cooled to room temperature
4. filtrationfiltered through a bed of celite
5. washThe filter cake was washed with methanol (75 mL)
6. concentrationthe combined filtrates were concentrated under reduced pressure
7. extractionextracted into methylene chloride (2×200 mL)
8. washThe combined organic layers were washed with brine (250 mL)
9. dry with materialdried over sodium sulfate

ORD record

ord-14b257da83df4d3faf4a2fb7e4287c8f

Source dataset

uspto-grants-1997_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05659045