Potassium Phosphate, Tribasic → HCID 71140780, Verbindung

Temperatur

60 °C

tert-Butyl 5-{[(Trifluoromethyl)sulfonyl]oxy}-3,3a,4,6a-tetrahydrocyclo-penta[c]pyrrole-2(1H)-carboxylate (8-2, 1.3 g, 3.64 mmol, 1.0 equiv), bis(pinocolato)diboron (1.0 g, 4.0 mmol, 1.1 equiv), potassium acetate (1.1 g, 10.91 mmol, 3.0 equiv) and PdCl2(dppf) (0.19 g, 0.26 mmol, 0.07 equiv) were added to anhydrous 1,4-dioxane (4.6 mL) and heated to 60° C. After 18 h, the reaction contents were cooled to RT, followed by the subsequent addition of water (0.93 mL), 5-chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro[1,2,5]-thiadiazole[3,4-b]pyridine 2,2-dioxide (23-2, 1.1 g, 3.64 mmol, 1.0 equiv), K3PO4 (1.9 g, 9.09 mmol, 2.5 equiv), (S)-Phos (0.15 g, 0.36 mmol, 0.10 equiv) and palladium(II) acetate (4.1 mg, 0.18 mmol, 0.05 equiv). The resulting mixture was heated to 70° C. for 9 h. Following this duration, LCMS showed consumption of starting material. The contents were then cooled to room temperature, diluted with ethyl acetate (20 mL), filtered through Celite and rinsed with ethyl acetate (3×5 mL) and water (1×5 mL). The filtrate layers were separated and the combined organics were washed with saturated NaHCO3 (10 mL). The combined aqueous layers were then back-extracted with ethyl acetate (3×5 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a dark orange oil. Purification by normal-phase chromatography (0-50% EtOAc:Hex) afforded 24-1 as a tan solid. MS m/z (M+H): calculated=482.5; observed=482.1.

1. customthe reaction contents
2. temperaturewere cooled to RT
3. temperatureThe resulting mixture was heated to 70° C. for 9 h
4. customconsumption of starting material
5. temperatureThe contents were then cooled to room temperature
6. additiondiluted with ethyl acetate (20 mL)
7. filtrationfiltered through Celite
8. washrinsed with ethyl acetate (3×5 mL) and water (1×5 mL)
9. customThe filtrate layers were separated
10. washthe combined organics were washed with saturated NaHCO3 (10 mL)
11. extractionThe combined aqueous layers were then back-extracted with ethyl acetate (3×5 mL)
12. dry with materialThe combined organics were dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto give a dark orange oil
16. customPurification by normal-phase chromatography (0-50% EtOAc:Hex)

ORD-Eintrag

ord-311d72be03cc477a9da6284cd6f566db

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09315518B2