Hydrochloric Acid → (5aS,8aR)-Ethyl 2-iodo-4-oxo-4,5,5a,6,8,8a-hexahydrofuro[3,4-e]pyrazolo[1,5-a]pyrazine-3-carboxylate

To an ice cold solution of Intermediate 352A (6.0 g, 11.5 mmol) in dioxane (20 mL) was added a 4 M solution of HCl in dioxane (100 mL, 11.47 mmol) and the reaction mixture was stirred at RT for 4 h. The reaction mixture was concentrated; the pH of the residue was adjusted to 8 with a 10% aqueous solution of NaHCO3 and the mixture was stirred at RT for 30 min. then was extracted with EtOAc (3×100 mL). The combined organic layers were washed with water, dried over Na2SO4, concentrated and kept under vacuum at 60° C. for 6 h to obtain Intermediate 352B as an off-white solid (2.1 g, 48%). MS(ES): −m/z=378 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.67 (d, J=3.5 Hz, 1H), 5.11-5.04 (m, 1H), 4.45 (dq, J=4.0, 6.5 Hz, 1H), 4.31-4.12 (m, 4H), 4.04-3.94 (m, 1H), 3.57 (dd, J=6.0, 9.0 Hz, 1H), 1.32-1.22 (m, 3H).

1. concentrationThe reaction mixture was concentrated
2. stirringthe mixture was stirred at RT for 30 min.
3. extractionthen was extracted with EtOAc (3×100 mL)
4. washThe combined organic layers were washed with water
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. waitkept under vacuum at 60° C. for 6 h

ORD record

ord-4933ac5f5f1246429786689958fdbbd6

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2