Hexane → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

Temperatur

-76 °C

A 3-liter four neck round-bottomed flask (flame dried) was charged 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (72.88 g, 0.25 mol), 4-fluoro-3-isopropoxy-N-methoxy-N-methylbenzamide (60.39 g, 0.25 mol) and dry THF (700 mL) under N2. The solution was cooled to −76° C., and a solution of n-BuLi in hexane (2.5M, 100 mL, 0.25 mol) was drop-wise maintaining the reaction mixture temperature below −70° C. over a period of 40 min. The reaction mixture was stirred at −76° C. for 1.5 h then quenched with 1N HCl (500 mL). The mixture was concentrated in vacuo to half the volume and was partitioned between EtOAc and H2O (v/v 1:0.3, 1 L). The organic phase was separated and the aqueous layer was extracted with EtOAc (500 mL). The combined organic extracts were washed with brine and then concentrated in vacuo to give a yellow oil which was purified by column chromatography using CH2Cl2 in hexanes (0% to 20%) to give (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a colorless oil contaminated with a by-product (49.0 g, 50%). LC-MS (10-90% MeOH in H2O with 0.1% TFA in a 2-min gradient) 393.2 (M+H), retention time=2.15 min.

1. customthen quenched with 1N HCl (500 mL)
2. concentrationThe mixture was concentrated in vacuo to half the volume
3. customwas partitioned between EtOAc and H2O (v/v 1:0.3, 1 L)
4. customThe organic phase was separated
5. extractionthe aqueous layer was extracted with EtOAc (500 mL)
6. washThe combined organic extracts were washed with brine
7. concentrationconcentrated in vacuo
8. customto give a yellow oil which
9. customwas purified by column chromatography

ORD-Eintrag

ord-acfc168000ca423dbbfa3e23edd5780c

Quelldatensatz

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07790770B2