p-Toluenesulfonic acid → Eosin

Beteiligte Stoffe

Reaktionsschritte

Reaction of 40.0 g of norbornadiene and 13.2 g of paraformaldehyde in formic acid (480 ml) containing concentrated sulfuric acid (20 drops) gave 55.3 g of diformate i. Oxidation of diformate i (55.3 g) in 900 ml of acetone at ##STR8## 0° C. with 553 ml of standard Jones reagent provided 27.2 g of keto acid ii. Treatment of 21.5 g ii with 225 ml of 48% hydrobromic acid in 225 ml of glacial acetic acid at reflux gave 28.1 g of bromo acid 1 (R2 =H, R3 =O). Esterification of 1 (R2 =H, R3 =O) with ethereal diazomethane gave methyl ester of formula (1) wherein R2 =Me, and R3 =O. Ketalization of 16.1 g of keto ester 1 (R2 =Me, R3 =O) with 35.8 g of 2-methyl-2-ethyl-1,3-dioxolane in 150 ml of benzene containing 2.7 g of p-toluenesulfonic acid at 25° C. for 20 hours give 17.0 g of pure ketal ester of formula (1) wherein R2 =Me and R3 =--O(CH2)2O--. Fluorination of 4.66 g of ester 1 (R2 =Me, R3 =--O(CH2)2O--) via enolate formation [lithium disopropylamide, tetrahydrofuran, -78° C.] and slow addition of perchloryl fluoride (-40° C.) resulted in an 86% isolated yield of a pure mixture of the desired α-fluoro ester shown in formula (2) (Rf 0.41) [hexane-ethyl acetate (4:1)] and the isomeric α-fluoro ester shown in formula (3) (Rf 0.33 in a ratio of 1:1.). Chromatography on silica gel easily provided the α-fluoro ester of formula (2), which was reduced with lithium aluminum hydride in ether at 25° C. and dehydrobrominated with 1,5-diaza-bicyclo(5.4.0)undec-5-ene (10 equivalents) in refluxing toluene. An 84% yield of the pure alcohol shown in formula (4) M+ 200.0850 was obtained. As fluorination with perchloryl fluoride can be hazardous, safety precautions should be observed.

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