Hydrochloric Acid → HCID 68690971, compound

Temperature

90 °C

To a mixture of (R)-2-N-(t-butoxycarbonyl)-10-bromo-8-trifluoromethyl-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one (61 mg, 0.135 mmol) and 2,4,6-trivinylcyclotriboroxane pyridine complex (33 mg, 0.135 mmol) in DME (2 mL) was added K2CO3 (20 mg, 0.135 mmol) and water (1 mL). The mixture was degassed under reduced pressure and purged with argon; tetrakis(triphenylphospine)palladium (0) (20 mg, 0.135 mmol) was added. The reaction mixture was heated to 90° C. for 18 h. The reaction was cooled to room temperature, and diluted with EtOAc (50 mL). The EtOAc layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford crude alkene 6a as a yellow oil. MS (ESI) 340 (M+H). Crude (R)-2-N-(t-butoxycarbonyl)-10-ethyl-8-trifluoromethyl-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one was dissolved in EtOH (2 mL) and hydrogenated [10% Pd/C (50 mg), H2 (30 psi)]. The reaction mixture was filtered through diatomaceous earth, and then purified by flash column chromatography (silica gel, 4:1 hexanes/EtOAc). The resulting material was deprotected using 4 N HCl in 1,4-dioxane (200 μL, 0.8 mmol), followed by trituration with diethyl ether, to provide the desired product (18 mg, 40% over 3 steps) as a white solid. MS (ESI) 299 (M+H).

1. customThe mixture was degassed under reduced pressure
2. custompurged with argon
3. temperatureThe reaction was cooled to room temperature
4. dry with materialThe EtOAc layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto afford crude alkene 6a as a yellow oil
8. filtrationThe reaction mixture was filtered through diatomaceous earth
9. custompurified by flash column chromatography (silica gel, 4:1 hexanes/EtOAc)

ORD record

ord-a61ed70cfb6644f89691ae541d04d106

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07244843B2