Reacción #1244300

Ecuación de reacción

cyclooctyne

4-(1-Fluoro-cyclooct-2-ynylmethyl)benzoic acid methyl ester

LiOH

→

4-(1-Fluoro-cyclooct-2-ynylmethyl)benzoic acid

Disolventes

dioxane

H2O

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe dioxane was removed on a rotary evaporator
2. 2
   workup.ADDITIONthe reaction mixture was diluted with CH2Cl2 (100 mL)
3. 3
   LavadoThe organic layer was washed with 1 N HC, (2×100 mL), H2O (3×100 mL), and brine (1×25 mL)
4. 4
   Secadodried over MgSO4
5. 5
   Otroyielding a white solid (1.7 g, 98%, Rf=0.30 in 27:3:1 hexane/EtOAc/AcOH), mp 132.0-132.5° C. (dec)

Procedimiento

To a solution of cyclooctyne 8b (1.8 g, 6.6 mmol) in dioxane (30 mL) and H2O (7.5 mL) was added finely crushed LiOH (3.1 g, 130 mmol). The suspension was heated to 50° C. and stirred for 3 h. The dioxane was removed on a rotary evaporator and the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with 1 N HC, (2×100 mL), H2O (3×100 mL), and brine (1×25 mL), and dried over MgSO4, yielding a white solid (1.7 g, 98%, Rf=0.30 in 27:3:1 hexane/EtOAc/AcOH), mp 132.0-132.5° C. (dec). IR: 3442, 2926, 2851, 2674, 2557, 2224, 1686, 1611 cm−1. 1H NMR (DMSO-d6, 400 MHz): δ 1.39 (app quintet, 1H, J=7.6 Hz), 1.64 (m, 2H), 1.76 (m, 2H), 2.10 (m, 5H), 3.07 (s, 1H), 3.11 (d, 1H, J=8.0 Hz), 7.38 (d, 2H, J=8.0 Hz), 7.87 (d, 2H, J=8.4 Hz), 12.9 (br s, 1H). 13C NMR (DMSO-d6, 100 MHz): δ 19.8, 25.7, 29.0, 33.7, 43.7 (d, J=25.0 Hz), 47.6 (d, J=25.0 Hz), 90.7 (d, J=32.0 Hz), 95.4 (d, J=173.0 Hz), 104.5 (d, J=10.0 Hz), 129.0, 129.2, 130.4, 141.2, 167.2. 19F NMR (CD3CN, 376 MHz): δ −139.4 (m). FAB—HRMS: Calcd. for C16H18O2F+ [M+H]+: 261.1291, found: 261.1291. Anal. calcd. for C16H17O2F: C, 79.31; H, 7.49. Found: C, 79.07; H, 7.26.

Fuente