Diisopropylamine → 5-(3-Benzyloxy-4-nitrobenzyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (0.31 mL, 2.19 mmol) in THF (5 mL) at 0° C. is added n-butyllithium (1.6 M in hexane, 1.37 mL, 2.19 mmol) dropwise and the solution is stirred at 0° C. for 20 min then is cooled to −78° C. To this is added a solution of 5,7,8,9-tetrahydrobenzocyclohepten-6-one (J. Med. Chem. 40, 3516 (1997)) (350 mg, 2.19 mmol) in 2 THF is added dropwise. After one hour, a solution of 1-benzyloxy-4-bromomethyl-2-nitrobenzene (705 mg, 2.19 mmol) in THF (2 mL) is added dropwise and the mixture is allowed to warm to RT overnight. The mixture is quenched with saturated NaHCO3 and the solution is extracted with EtOAc. The organic layer is washed with water, brined and dried over MgSO4. The solvent is removed under reduced pressure and the residue is purified by flash chromatography using a gradient of 25-75% hexane/CH2Cl2 to give the title compound as a yellow liquid. 1H NMR (CDCl3): 7.72-7.70 (d, J=8.08 Hz, 1H), 7.42-7.11 (m, 8H), 6.92-6.90 (dd, J=1.27 Hz, 8.08 Hz, 1 H), 6.73-6.72 (m, 2H), 5.05-5.04 (d, J=2.78 Hz, 2H), 4.0-3.96 (t, J=7.08 Hz, 1H), 3.57-3.51 (q, J=7.58 Hz, 1H), 3.05-3.01 (q, J=6.06 Hz, 1H), 2.87-2.81 (m, 1H), 2.65-2.58 (m, 1H), 2.55-2.47 (m, 1H), 2.42-2.37 (m, 1H), 2.05-1.95 (m, 1H), 1.92-1.83 (m, 1H). (M−1)−=400.

Provenance & Evidence