Benzophenone imine → HCID 68689435, compound

A solution of tris(dibenzylideneacetone)dipalladium(0) (14 mg, 15 μmol) and 2-(di-tert-butylphosphino)biphenyl (14.0 mg, 46 μmol) in anhydrous toluene (5.5 mL) was degassed with argon for 15 min at room temperature, then N-(t-butoxycarbonyl)-(R)-1,3,4,10b-tetrahydro-9-bromo-7-trifluoromethyl-pyrazino[2,1-a]isoindol-6(2H)-one (110 mg, 0.25 mmol) was added. Upon further degassing, benzophenone imine (0.14 mg, 0.75 mmol) and sodium tert-butoxide (73 mg, 0.75 mmol) were added. The mixture was degassed a final time and then subjected to microwave conditions (150 W, 150° C.) for 1 h. Upon cooling to room temperature, the mixture was filtered through a pad of diatomaceous earth and the pad was washed with EtOAc (100 mL). The filtrate was concentrated in vacuo and the residue was dissolved in MeOH (10 mL) and cooled to 0° C. To this solution was added sodium acetate (95 mg, 1.4 mmol) and hydroxylamine hydrochloride (150 mg, 1.8 mmol). The reaction was warmed to room temperature and stirred for 1.5 h. Additional amounts of sodium acetate (95 mg, 1.4 mmol) and hydroxylamine hydrochloride (150 mg, 1.8 mmol) were added at 0° C. and the reaction was stirred at room temperature for an additional 2.5 h. The solution was concentrated in vacuo and the residue was partitioned between CH2Cl2 (50 mL) and 1 N NaOH (50 mL). The aqueous phase was extracted with CH2Cl2 (4×75 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 5–33% EtOAc/hexanes) to provide the product (47 mg) in 50% yield. MS (APCI) 372 (M+H).

1. customThe mixture was degassed a final time
2. filtrationthe mixture was filtered through a pad of diatomaceous earth
3. washthe pad was washed with EtOAc (100 mL)
4. concentrationThe filtrate was concentrated in vacuo
5. dissolutionthe residue was dissolved in MeOH (10 mL)
6. temperaturecooled to 0° C
7. temperatureThe reaction was warmed to room temperature
8. stirringthe reaction was stirred at room temperature for an additional 2.5 h
9. concentrationThe solution was concentrated in vacuo
10. customthe residue was partitioned between CH2Cl2 (50 mL) and 1 N NaOH (50 mL)
11. extractionThe aqueous phase was extracted with CH2Cl2 (4×75 mL)
12. dry with materialThe combined organic phases were dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe residue was purified by flash column chromatography (silica gel, 5–33% EtOAc/hexanes)

ORD record

ord-0cdc5092c53c4df3b76146a003caadd5

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07244843B2