Azobisisobutyronitrile → HCID 21180691, compound

Participants

Reaction Steps

A solution of 2.25 g (6.7 mmol) of ethyl 3-(1-(t-butoxycarbonyl)-piperidin-4-yl)-3-hydroxy-2,2-difluoropropionate (from EXAMPLE 176, Step A) and 2.50 g (20.5 mmol) of 4-(N,N-dimethylamino)pyridine in 40 mL of CH2Cl2 at 0° C. was treated with 1.10 mL (12.0 mmol) of methyl chlorooxoacetate. The resulting mixture was warmed to rt, stirred for 1 h, then quenched with 100 mL of 0.5 N KHSO4. The quenched mixture was extracted with 250 mL of EtOAc; the extract was dried and concentrated. The crude oxalate ester, 3.70 mL (12.0 mmol) of tris(trimethylsilyl)silane and 500 mg (3.0 mmol) of 2,2′-azobisisobutyronitrile in 20 mL of toluene was heated at reflux under an Ar atmosphere for 1.5 h. The reaction mixture was cooled and concentrated. Flash chromatography on 75 g of silica gel using 10:1 v/v, then 4:1 v/v hexanes/ether as the eluants afforded 922 mg (43%) of the title compound as an oil: 1H NMR (500 MHz, CDCl3) δ 1.16-1.25 (m, 2H), 1.36 (t, J=7.0, 31), 1.46 (s, 9H), 1.74 (app d, J=15.0, 2H), 1.75-1.81 (m, 1H), 2.02 (dt, J=6.0, 18.0,22H), 2.68-2.73 (m, 2H), 4.05-4.09 (m, 2H), 4.33 (q, J=7.0, 2H).

Provenance & Evidence