Ammonium Hydroxide → 7-Chlorothieno[3,2-b]pyridine

Temperature

100 °C

To neat POCl3 (200 mL, 2146 mmol) at 60° C. in a 500 mL round-bottom flask was added thieno[3,2-b]pyridin-7-ol (1 eq., 200 g, 1323 mmol) in small portions over 1.5 h. The reaction mixture was heated at 60° C. for 1 h and at 100° C. for an additional hour. After cooling down to 0° C., the reaction mixture was poured onto crushed ice (1 L) over a period of 30 min. After 15 min, NH4OH (1.5 L) was added to the mixture to form a grey precipitate that was collected by filtration, washed with water (50 mL) and air dried. The dry solid was suspended in EtOAc (1 L). The slurry was stirred at r.t. for 15 min, filtered and the filter was washed with EA (2×100 mL). The organic phase was collected, dried over MgSO4 and concentrated. The residue was passed through a short silica gel pad (300 g, eluent—a gradient hexane/EtOAc, 8/2 to 5/5) and dried in the vacuum oven (35° C.) for 2 h to afford 6 as a off-white solid (214.8 g, 1266 mmol, 96% yield). MS (m/z): 170.0 (M+H). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.64 (d, J=5.1 Hz, 1H) 8.25 (d, J=5.5 Hz, 1H), 7.66 (d, J=5.5 Hz, 1H), 7.54 (d, J=5.1 Hz, 1H).

1. temperatureAfter cooling down to 0° C.
2. additionthe reaction mixture was poured
3. customto form a grey precipitate that
4. filtrationwas collected by filtration
5. washwashed with water (50 mL) and air
6. customdried
7. filtrationfiltered
8. washthe filter was washed with EA (2×100 mL)
9. customThe organic phase was collected
10. dry with materialdried over MgSO4
11. concentrationconcentrated
12. dry with materialeluent—a gradient hexane/EtOAc, 8/2 to 5/5) and dried in the vacuum oven (35° C.) for 2 h

ORD record

ord-f6715120c9e944cdb55e735994f794db

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569503B2