Sodium hydride → Methyl 4-((2rs)-2-{[1-(4-tert-butylbenzyl)-5-chloro-1h-indol-2-yl]carbonyl}pentyl)benzoate

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Reaction Steps

To a solution of the title compound of Example 3 Step D (240 mg, 0.63 mmol) in DMF (2.5 mL) was added NaH (30 mg, 60% suspension in mineral oil, 0.75 mmol). After 15 min, 4-tert-butylbenzyl bromide (0.126 mL, 0.69 mmol) was added, and the resultant mixture was stirred for 1.5 h, whereupon it was quenched by addition of sat. aq. NH4Cl. The aqueous phase was extracted with EtOAc, and the organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 25%, then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS B, tr=3.30 min, m/z 530.3 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J=8.5 Hz, 2H), 7.63 (d, J=2.0 Hz, 1H), 7.29-7.23 (m, 4H), 7.15 (d, J=8.0 Hz, 2H), 7.13 (s, 1H), 6.82 (d, J=8.5 Hz, 2H), 5.78 (ABq, J=16.0 Hz, Δν=71.0 Hz, 2H), 3.87 (s, 3H), 3.62 (dddd, J=8.5, 8.5, 5.5, 5.5 Hz, 1H), 3.08 (dd, J=14.0, 8.5 Hz, 1H), 2.78 (dd, J=14.0, 5.5 Hz, 1H), 1.76-1.70 (m, 1H), 1.52-1.45 (m, 1H), 1.26 (s, 9H), 1.23-1.18 (m, 2H), 0.81 (t, J=7.5 Hz, 3H).

Provenance & Evidence