tert-Butanol → Ammonium Hydroxide

To a suspension of (±)-sodium 2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylate (1.64 g, 5.83 mmol, described in Intermediate 7) and triethylamine (1.62 mL, 11.7 mmol) in tert-butanol (50 mL) was added diphenylphosphoryl azide (1.89 mL, 8.75 mmol) and the mixture was heated at reflux for 72 h. Additional diphenylphosphoryl azide (1.89 mL, 8.75 mmol) was added after 24 h and 56 h. The reaction mixture was concentrated in vacuo and then partitioned between CH2Cl2 (75 mL) and saturated NaHCO3 (100 mL). The organic layer was separated and the aqueous layer was further extracted with CH2Cl2 (2×50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH: NH4OH—100:0:0 to 95:5:1, to give the title compound. MS: m/z=353 (M+1).

1. temperaturethe mixture was heated
2. temperatureat reflux for 72 h
3. concentrationThe reaction mixture was concentrated in vacuo
4. custompartitioned between CH2Cl2 (75 mL) and saturated NaHCO3 (100 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer was further extracted with CH2Cl2 (2×50 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by silica gel chromatography
11. washeluting with a gradient of CH2Cl2

ORD record

ord-3be143d9a1c34366b12b322e9d70768b

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765759B2