Hydrochloric Acid → tert-Butyl ((5S,6R)-6-methyl-2-oxo-5-(2,3,5-trifluorophenyl)piperidin-3-yl)carbamate

Temperature

55 °C

To a solution of NaBO3.4H2O (1.5 g, 3.9 mmol) in H2O (18.2 g) was charged isopropylamine (1.16 g, 19.6 mmol) dropwise at 20° C. After the mixture was stirred for 30 min, the pH was adjusted to 10.2-10.3 by 6N HCl. PLP (0.042 g, 0.27 mmol) and ATA-412 (1.0 g) was charged to the solution at 20° C. After the above mixture was stirred for 1 h, a solution of 45 (2 g, 4.7 mmoL) in DMSO (10 mL) was added slowly at 20° C. The solution was heated to 55° C. and stirred for 24 h. After the reaction was complete, the reaction was quenched by isopropyl alcohol (10 mL), and then partitioned with water and IPAc. The organic solution was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-20% EtOAc/PE) to give 46 (1.45 g, 85% yield). 1H NMR (DMSO-d6, 400 MHz): δ 7.95-7.78 (m, 1H), 6.95 (m, 1H), 3.01 (t, 1H), 1.36 (s, 9H), 1.17-1.10 (br, 4H), 1.12 (m, 3H); MS (ESI) m/e [M+H]+: 359.15.

1. additionPLP (0.042 g, 0.27 mmol) and ATA-412 (1.0 g) was charged to the solution at 20° C
2. stirringAfter the above mixture was stirred for 1 h
3. stirringstirred for 24 h
4. customthe reaction was quenched by isopropyl alcohol (10 mL)
5. custompartitioned with water and IPAc
6. dry with materialThe organic solution was dried over Na2SO4
7. concentrationconcentrated
8. customThe crude residual was further purified by flash chromatography on silica gel (5-20% EtOAc/PE)

ORD record

ord-a93129f480c34c61bc6fb38d5c32ebfa

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174989B2