1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86684784, compound

Participants

Reaction Conditions

Reaction Steps

1,8-Diazabicyclo[5.4.0]undec-7-ene (0.12 mL, 0.80 mmol, Aldrich) was added dropwise to a suspension of Lithium chloride (35.9 mg, 0.847 mmol, Aldrich) and Methyl [bis(methyloxy)phosphoryl]{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}acetate (Tetrahedron Lett. 1981, 22, 663-666) (265 mg, 0.847 mmol) in dry Acetonitrile (16 mL) and the mixture was maintained at 0° C. for 1 h. A solution of (2R,4S)-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-4-{[(1,1-dimethylethyl)sulfinyl]amino}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-(2-oxoethyl)-1-piperidinecarboxamide (Intermediate 9, 378 mg, 0.58 mmol) in Acetonitrile (5 mL) was added dropwise at 0° C. The mixture was stirred for 7 hours while the temperature was allowed to increase to 25° C. Saturated aqueous NaHCO3 and EtOAc were added to the reaction mixture and the two phases were separated. The combined organic phases were dried (Na2SO4) and evaporated to dryness. The crude was purified by flash chromatography on silica with SP1 (Biotage) system (from 1:0 to 0:1 Cyclohexane/EtOAc) to give the title compound (186 mg, 0.22 mmol, 38% yield) as a white foam. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.98 (m, 1H) 7.68 (s, 2H) 7.12-7.20 (m, 1H) 6.92 (d, 1H) 6.79 (t, 1H) 5.66 (t, 1H) 5.26-5.35 (m, 1H) 5.00 (s, 1H) 4.33 (d, 1H) 3.71 (s, 3H) 2.70 (s, 3H) 2.60-3.4 (m, 4H) 2.27 (s, 3H) 1.48 (d, 3H) 1.35-2.10 (m, 4H) 1.05-1.13 (m, 9H) 0.84-0.98 (m, 9H) 0.06 (s, 6H). The sample consists of two species ratio ˜3:1 most probably E and Z isomers (see the signals of OMe at 3.71 ppm). UPLC: 2 close peaks Rt 0.86 and 0.89 mins, m/z=838 [M+H]+.

Provenance & Evidence