Potassium Carbonate → (1R,2S,3R,4R,5R)-2-Amino-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)cyclohexanol

A suspension of (1R,2S,3R,4R,5R)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)-2-((tert-butoxycarbonyl)amino)cyclohexyl 4-nitrobenzoate (2.80 g, 4.02 mmol) and anhydrous K2CO3 (0.70 g, 0.51 mmol) in MeOH (100 mL) was stirred at room temperature for 2 h. The resulted clear solution was concentrated, and DCM (80 mL) was added. The mixture was washed with saturated aqueous NaHCO3 (60 mL), and the aqueous layer was further extracted with DCM (2×40 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:3 to 1:1), affording a white solid. The solid was dissolved in mixed MeOH and EtOAc (30 mL, 2:1). HCl (g) was bubbled into the solution for 30 sec, and the mixture was stirred at room temperature for 2 h. The solvent was then removed, water (30 mL) was added and the mixture was basified with diluted aqueous NaOH solution. Extraction with DCM (2×40 mL) was performed, and the combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, affording the title compound as an off-white solid (1.54 g, 94%). 1H NMR (400 MHz, CDCl3) δ 7.37-7.25 (m, 15H), 4.98 (d, J=11.3 Hz, 1H), 4.84 (d, J=10.8 Hz, 1H), 4.69 (d, J=11.3 Hz, 1H), 4.56 (d, J=10.8 Hz, 1H), 4.47 (s, 2H), 3.64 (dd, J=4.9, 8.9 Hz, 1H), 3.54-3.48 (m, 2H), 3.34-3.30 (m, 1H), 3.19 (t, J=9.4 Hz, 1H), 2.53-2.50 (m, 1H), 2.08-2.02 (m, 1H), 1.75-1.72 (m, 1H), 1.59-1.52 (m, 1H).

1. concentrationThe resulted clear solution was concentrated
2. additionDCM (80 mL) was added
3. washThe mixture was washed with saturated aqueous NaHCO3 (60 mL)
4. extractionthe aqueous layer was further extracted with DCM (2×40 mL)
5. extractionThe combined extract
6. dry with materialwas dried over anhydrous Na2SO4
7. filtrationAfter filtration the solvent
8. customwas evaporated under reduced pressure
9. customthe residue was purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:3 to 1:1)
10. customaffording a white solid
11. customHCl (g) was bubbled into the solution for 30 sec
12. stirringthe mixture was stirred at room temperature for 2 h
13. customThe solvent was then removed
14. additionwater (30 mL) was added
15. extractionExtraction with DCM (2×40 mL)
16. extractionthe combined extract
17. dry with materialwas dried over anhydrous Na2SO4
18. filtrationAfter filtration the solvent
19. customwas evaporated under reduced pressure

ORD record

ord-d31634bf2af64b3d94396a24e17be3d9

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09126957B2