Hydrochloric Acid → HCID 59403544, compound

Participants

Reaction Steps

To a solution of diisopropylamine (15.15 ml, 106 mmol) in dry THF (650 m) at −78° C. under Ar was added nBuLi (44.3 ml, 70.9 mmol) down the side of the flask and the resulting solution stirred for 1 h. A solution of 3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2-methylbenzonitrile Preparation 21) (12.54 g, 35.4 mmol) in dry THF (100 ml) under Ar was added dropwise at ˜10 mlmin−1, and the resulting dark blue solution stirred at −78° C. for 45 min. Allyl bromide (6.13 ml, 70.9 mmol) was added dropwise at ˜3 mlmin−1, and the resulting dark red solution stirred for 30 min at −78° C. 1 M HCl (aq) (375 ml) was added, the mixture allowed to warm to RT then the layers separated. The aqueous was extracted with EtOAc (2×125 ml), then the combined organics washed with brine (250 ml), dried (MgSO4), filtered and concentrated in vacuo to give a crude red oil (12.8 g). This was redissolved in DCM (20 ml) and added to a pre-wet (isohexane) column of silica (5 cm×5 cm). Elution with EtOAc-isohexane (1:3) and concentration of the desired fractions gave a pale orange solid 2-(3-buten-1-yl)-3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)benzonitrile (9.50 g, 20.98 mmol, 59.2% yield). 1H NMR (400 MHz, CDCl3) δ 8.26 (1H, d), 8.24 (1H, d), 8.05 (1H, dd), 7.79 (1H, d), 7.46 (1H, t), 7.07 (1H, d), 5.94 (1H, ddt), 5.07 (1H, dq), 5.01 (1H, dd), 4.73 (1H, sept), 3.40 (2H, t), 2.47 (2H, qd), 1.45 (6H, d); MS (ES) C22H2035ClN3O2 requires 393; found 394 [M+H]+.

Provenance & Evidence