Phosphorus oxychloride → 2-Chloro-5-(3-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine

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Reaction Conditions

Reaction Steps

A suspension of 5 (16.52 g, 72.4 mmol) in neat P(O)Cl3 (21.5 mL, 0.231 mol) was stirred at 100-105° C. for 4 h. The mixture was then cooled to r.t., diluted with p-xylene (100 mL) and concentrated to dryness in vacuum. The residue was separated between saturated aqueous NaHCO3—AcOEt. 10% aqueous solution of Na2CO3 was added to basify the aqueous layer to pH 9. Organic phase was separated and the aqueous layer was extracted with AcOEt (8×300 mL). Combined organic solutions were dried MgSO4, concentrated, and the residue was purified by silicagel chromatography (SGC) using CH2Cl2:AcOEt as eluent in gradient to afford recovered starting material 5 (0.76 g, 5%). The desired product was then crystallized from acetone to afford 6 (10.06 g, 56%), thin tan needles. 1H NMR (400 MHz, CDCl3) δ 6.47 (s, 1H), 7.08 (tdd, J=8.1, 2.3, 1.5 Hz, 1H), 7.33 (ddd, J=9.9, 2.3, 1.6 Hz, 1H), 7.38-7.48 (m, 2H), 8.03 (d, J=2.1 Hz, 1H), 8.53 (d, J=2.1 Hz, 1H), 11.46 (bs, 1H).

Provenance & Evidence