2,2,3,3-tetrafluorocyclobutan-1-ol

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tert-butyl (5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamate (137) (0.35 g, 1.15 mmol) was dissovled in dichloromethane (5 mL) and followed by addition of DIEA (0.6 mL, 3.45 mmol) and MsCl (197 mg, 1.72 mmol). The reaction was stirred for 10 minutes. The mixture was diluted with dichloromethane (10 mL) and washed with water. The organic layers were combined, dried over Na2SO4, filtered and concentrated to give a residue which was dissolved in 2,2,3,3-tetrafluorocyclobutanol (2 mL) and followed by addition of K2CO3(476 mg, 3.45 mmol). The reaction mixture was heated at 90° C. for 2-3 hours. The mixture was diluted with water (10 mL) and extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered and concentrated. To this residue was added TFA (1 mL) and stirred for 15 minutes. Then aqueous Na2CO3(2M, 20 mL) was added and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated. Purification by column chromatography on silica gel gave 2-methyl-5-(5-((2,2,3,3-tetrafluorocyclobutoxy)methyl)-1,2,4-oxadiazol-3-yl)aniline (138). 1H NMR (400 MHz, CDCl3) δ 9.36 (bs, 2H), 8.12 (d, J=1.2 Hz, 1H), 7.91 (dd, J=1.2, 8.0 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 4.95 (dd, J=14.4, 68.4 Hz, 2H), 4.51 (m, 1H), 2.95 (m, 1H), 2.51-2.68 (m, 4H). MS m/z 332.0 (M+1)+. washed with water dried over Na2SO4 filtered concentrated to give a residue which extracted with EtOAc dried over Na2SO4 filtered concentrated To this residue was added TFA (1 mL) stirred for 15 minutes Then aqueous Na2CO3(2M, 20 mL) was added extracted with EtOAc The organic layers were dried over Na2SO4 filtered concentrated Purification by column chromatography on silica gel