Cesium carbonate → HCID 66756714, Verbindung

Temperatur

80 °C

(3-Benzyloxy-4-nitrophenyl)-acetic acid ethyl ester (Step C) (1.90 g, 6.03 mmol) and 2-benzyloxy-6-fluorobenzonitrile (Step D) (2.74 g, 12.1 mmol) are dissolved in DMF (18 mL) and added dropwise to a suspension of Cs2CO3 (5.89 g, 18.1 mmol) in DMF (18 mL). The mixture is heated to 80° C. for 1.5 h, then stirred at 60° C. for 16 h. The mixture is diluted with EtOAc (350 mL) and extracted with 1N HCl (2×75 mL), followed by brine (75 mL). The organic phase is dried over Na2SO4 and concentrated. The residue is taken up in THF (18 mL), MeOH (18 mL) and 1N NaOH (36 mL). Decarboxylation is complete after 2 h, the reaction mixture is poured into ice water (100 mL) and acidified to pH ˜2 with 6N HCl. The mixture is extracted with EtOAc (2×200 mL) and the organic phase is washed with brine (75 mL), dried over Na2SO4 and concentrated to afford a brown oil. Purification by flash column (10-75% EtOAc/hexanes) affords 2-benzyloxy-6-(3-benzyloxy-4-nitrobenzyl)-benzonitrile as an off-white solid: MS (M+H)+=451.

1. extractionextracted with 1N HCl (2×75 mL)
2. dry with materialThe organic phase is dried over Na2SO4
3. concentrationconcentrated
4. waitDecarboxylation is complete after 2 h
5. additionthe reaction mixture is poured into ice water (100 mL)
6. extractionThe mixture is extracted with EtOAc (2×200 mL)
7. washthe organic phase is washed with brine (75 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customto afford a brown oil
11. customPurification by flash column (10-75% EtOAc/hexanes)

ORD-Eintrag

ord-00bf8f5ff598478faba2a154eb9d0b80

Quelldatensatz

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08119666B2