Hydrochloric Acid → (1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-ol

To a stirred solution of Intermediate 1c (117 g, 451 mmol) in methanol (0.7 L), 6N aqueous sodium hydroxide solution (190 mL, 1.14 mol) was added and stirred at RT for 20 h. The mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (1 L) and water (0.5 L). Concentrated HCl solution (95 mL, 1.14 mol) was added slowly with stirring. Additional HCl was used to adjust the pH of the aqueous layer to pH=2. The mixture was then separated and the organic layer was extracted with HCl solution (2M aqueous, 3×500 mL). The combined aqueous layers were basified to pH˜12, by addition of concentrated aqueous NH4OH solution, and then extracted in to ethyl acetate (5×750 mL). The combined organic extracts were washed with brine (200 mL), dried (Na2SO4), filtered and concentrated in vacuo to give a solid (50.8 g). This material was recrystallized (cyclohexane/ethyl acetate[2:1], 350 mL) to provide Intermediate 1. (44.4 g, 60%). 1H NMR (400 MHz, d6-DMSO): 1.66-1.90 (4H, m), 3.71-3.77 (1H, t, J=5.4 Hz), 4.46-4.54 (1H, t, J=5.4 Hz), 7.14-7.22 (2H, m), 7.32-7.38 (1H, m), 7.40-7.46 (1H, m).

1. concentrationThe mixture was concentrated in vacuo
2. additionthe residue was diluted with ethyl acetate (1 L) and water (0.5 L)
3. stirringwith stirring
4. customThe mixture was then separated
5. extractionthe organic layer was extracted with HCl solution (2M aqueous, 3×500 mL)
6. additionThe combined aqueous layers were basified to pH˜12, by addition of concentrated aqueous NH4OH solution
7. extractionextracted in to ethyl acetate (5×750 mL)
8. washThe combined organic extracts were washed with brine (200 mL)
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-0072e27c80c6482e9dee545bcde5f233

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359354B2