Hydrochloric Acid → HCID 21927758, compound

Temperature

75 °C

The pyrazinone, 1-benzyloxycarbonylmethyl-3-dichloro-6-(3-nitrophenyl)pyrazinone (EX-100A), (15.01 g, 34.6 mmol) was taken up in 325 mL of 50% EtOH (w/w) and heated to 75° C. EtOAc was added until the solution was homogeneous (about 80 mL). Iron powder (9.4 g, 168 mmol) was added, followed by 0.57 mL of 12 M HCl (6.8 mmol) in about 0.6 mL of 50% EtOH. The reaction was monitored by TLC (80% EtOAc/hexanes) and was complete within 40 minutes. The reaction mixture was cooled to room temperature, and the iron was removed by filtration through Celite. The yellow solution was diluted with 600 mL of EtOAc and 300 mL of water. Saturated NaCl was added to help separate the layers. The organic phase was washed with saturated NaHCO3 (2×250 mL), saturated NaCl (1×250 mL), dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The residue was taken up in 20–25 mL of 3.4 M HCl in EtOAc. Additional EtOAc (about 25 mL) was added, and the mixture was heated to dissolve all of the compound. The volatile components were removed under reduced pressure. The residue (crusty solid) was taken up in EtOAc and slowly dripped into hexanes. The pale yellow solid that precipitated was filtered and dried under vacuum at room temperature to yield 12.19 g (80% yield) of 1-benzyloxycarbonylmethyl-3,5-dichloro-6-(3-aminophenyl)pyrazinone hydrochloride (EX-100B) as a pale yellow solid: 1H NMR (300 MHz, CD3OD) δ 4.61 (AB q, 2H, J=17 Hz), 5.20 (AB q, 2H, J=12 Hz), 7.31–7.51 (m, 7H), 7.63–7.67 (m, 2H); HPLC purity (retention time): 91% (3.0 min); LRMS m/z 404 (M++H).

1. temperatureThe reaction mixture was cooled to room temperature
2. customthe iron was removed by filtration through Celite
3. additionThe yellow solution was diluted with 600 mL of EtOAc and 300 mL of water
4. additionSaturated NaCl was added
5. customto help separate the layers
6. washThe organic phase was washed with saturated NaHCO3 (2×250 mL), saturated NaCl (1×250 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customthe solvents were removed under reduced pressure
10. additionAdditional EtOAc (about 25 mL) was added
11. temperaturethe mixture was heated
12. dissolutionto dissolve all of the compound
13. customThe volatile components were removed under reduced pressure
14. filtrationThe pale yellow solid that precipitated was filtered
15. customdried under vacuum at room temperature

ORD record

ord-ba5d4b99f8004f6d8130bb5c79aabf31

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07119094B1