Hydrochloric Acid → HCID 56950691, compound

A 20 L 3-neck flask, equipped with mechanical stirrer, addition funnel and thermometer was charged with a solution of compound 61 (740 g, 4.02 mol) in anhydrous CH2Cl2 (8.0 L) followed by several drops of DMF. The solution was degassed with N2 for 3 min (COCl)2 (880 g, 6.93 mol) was added to the stirring reaction mixture slowly and carefully at 25˜27° C. over 45 min. A lot of gas was generated. After stirring at 25˜27° C. for 60 min, the reaction mixture was concentrated to dryness under reduced pressure. The residual oil was re-dissolved in anhydrous CH2Cl2 (2.0 L), concentrated to dryness again and further dried with under reduced pressure for 40 min to give black oil that was dissolved in anhydrous CH2Cl2 (8.0 L). PhOH (460 g, 4.9 mol) was added to the stirred solution at 25˜30° C., followed by Et3N (824 g, 8.16 mol). After DMAP (4.9 g, 0.04 mol) was added to the reaction, the reaction mixture was stirred at 20-30° C. for 16 h. Aqueous HCl (2.0 L, 3N) was added to the reaction mixture below 30° C. The organic layer was separated and washed with 3N aqueous HCl (2×1 L). The organic layer was concentrated to dryness under reduce pressure to give brown oil that was dissolved in EtOAc (4.0 L) and washed with 0.5N aqueous (3×1.0 L) and brine (2×1.0 L). The above acid aqueous layer was extracted with EtOAc (2×1.0 L) and the extracts were combined with the above EtOAc solution. The organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated under reduce pressure to afford crude compound 62 (1100 g) as brown partially crystalline slurry (>100% yield): 1H NMR (400 MHz, CDCl3) δ 7.47-7.41 (m, 2H), 7.31-7.24 (m, 3H), 7.08 (dd, J=9.2, 9.2 Hz, 1H), 6.77 (dd, J=9.2, 3.7 Hz, 1H), 3.88 (s, 3H), 2.36 (d, J=2.3 Hz, 3H); MS (ESI) m/z 261.12 (M+H).

1. customA 20 L 3-neck flask, equipped with mechanical stirrer, addition funnel
2. additionwas added to the stirring reaction mixture slowly
3. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
4. dissolutionThe residual oil was re-dissolved in anhydrous CH2Cl2 (2.0 L)
5. concentrationconcentrated to dryness again
6. customfurther dried with under reduced pressure for 40 min
7. customto give black oil that
8. stirringthe reaction mixture was stirred at 20-30° C. for 16 h
9. customThe organic layer was separated
10. washwashed with 3N aqueous HCl (2×1 L)
11. concentrationThe organic layer was concentrated to dryness
12. customto give brown oil that
13. washwashed with 0.5N aqueous (3×1.0 L) and brine (2×1.0 L)
14. extractionThe above acid aqueous layer was extracted with EtOAc (2×1.0 L)
15. dry with materialThe organic layer was dried over Na2SO4
16. filtrationfiltered
17. concentrationThe filtrate was concentrated

ORD record

ord-3966ce6b81b448f19627555deeed6329

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073829B2