Hydrochloric Acid → HCID 59369867, compound

Temperature

0 °C

To a vigorously stirred solution diethyl ether (215 mL) in 40% KOH (160 mL) in a plastic bottle at 0° C. was added 1-methyl-3-nitrosoguanidine (15.5 g, 105 mmol) over a period of 5 minutes and stirred for 0.5 h at 0° C. The mixture was then transferred to a plastic separatory funnel from which the aqueous phase was separated from the organic phase. The organic phase was then added very slowly over a period of 0.5 h to a plastic bottle containing a solution of 7-7 (6.4 g, 32.5 mmol) in diethyl ether (130 mL) at 0° C. and stirred overnight. The system was then bubbled through with nitrogen for 0.5 h and the reaction contents were poured in to a round bottom flask and the contents were concentrated in vacuo to yield a yellow solid. To a solution of this yellow solid (1.0 g, 4.19 mmol) in DMF (8 mL) at 25° C. was added cesium carbonate (2.04 g, 6.28 mmol) and iodomethane (0.314 mL, 5.0 mmol) and the system was stirred overnight. The mixture was diluted with EtOAc and washed with water. The combined organic layers were dried over MgSO4 and concentrated to a gold oil. To this gold oil (1.0 g, 3.96 mmol) in DCM (8 mL) at 25° C. was added lead tetraacetate (2.63 g, 5.94 mmol) and the system was stirred for 2 h. The system was cooled to 0° C. and any excess lead tetraacetate was destroyed with a drop of acetic acid and 3 drops of hydrazine hydrate. The mixture was then dried over potassium carbonate, concentrated and purified by normal phase silica gel chromatography (0 to 100% EtOAc in hexanes) to afford a white solid. To a solution of this white solid (0.466 g, 1.85 mmol) in THF (2.0 mL) and MeOH (2.0 mL) at 25° C. was added a 1M solution of KOH (2.79 mL, 2.79 mmol) and the system was stirred overnight. The mixture was then neutralized with 1N HCl to a pH of 5. Solvent was then removed in vacuo and the residue was azeotroped 2× with toluene to afford the title compound as a yellow powder. ESI+ MS: [M+H]÷ 237.2.

1. customThe mixture was then transferred to a plastic separatory funnel from which
2. customthe aqueous phase was separated from the organic phase
3. additionThe organic phase was then added very slowly over a period of 0.5 h to a plastic bottle
4. stirringstirred overnight
5. customThe system was then bubbled through with nitrogen for 0.5 h
6. customthe reaction contents
7. additionwere poured in to a round bottom flask
8. concentrationthe contents were concentrated in vacuo
9. customto yield a yellow solid
10. stirringthe system was stirred overnight
11. washwashed with water
12. dry with materialThe combined organic layers were dried over MgSO4
13. concentrationconcentrated to a gold oil
14. stirringthe system was stirred for 2 h
15. temperatureThe system was cooled to 0° C.
16. customany excess lead tetraacetate was destroyed with a drop of acetic acid and 3 drops of hydrazine hydrate
17. dry with materialThe mixture was then dried over potassium carbonate
18. concentrationconcentrated
19. custompurified by normal phase silica gel chromatography (0 to 100% EtOAc in hexanes)
20. customto afford a white solid
21. stirringthe system was stirred overnight
22. customSolvent was then removed in vacuo
23. customthe residue was azeotroped 2× with toluene

ORD record

ord-04d4d2fe0a8749328209e48ac6d8a70c

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030495B2