HCID 59161318, compound → HCID 59161248, compound

Participants

Reaction Conditions

Reaction Steps

Dissolve (R)-N-(6-bromo-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (Preparation 21) (1.00 g, 2.98 mmol) in 1-methyl-2-pyrolidinone (30 mL). Sparge the resulting solution with nitrogen for 15 min. Add copper(I) cyanide (801 mg, 8.95 mmol) and copper(I) iodide (1.70 g, 8.95 mmol). Heat to 130° C. for three days, then cool to room temperature. Dilute the reaction mixture with water (100 mL), EtOAc (250 mL), and enough ethylene diamine to dissolve the copper solids (about 70 mL). Separate the layers, then wash the organic layer with water (2×50 mL). Dry the organic portion over MgSO4. Filter, concentrate, and purify on silica gel (80 g) using 50-80% EtOAc/hexanes to afford 530 mg (63%) of the title compound as a white solid. MS (ES): 282 (M+1), 280 (M−1); 1H NMR (CDCl3): δ 8.44 (s, 1H), 7.76 (s, 1H), 7.40 (dd, 1H, J=8.4, 1.3 Hz), 7.37 (d, 1H, J=8.5 Hz), 5.64 (d, 1H, J=7.5 Hz), 4.42 (m, 1H), 3.11 (dd, 1H, J=15.2, 5.1 Hz), 2.98-2.80 (m, 2H), 2.59 (dd, 1H, J=15.4, 7.5 Hz), 2.38 (m, 1H), 2.17 (m, 1H), 2.02 (m, 1H), 1.21 (d, 6H, J=7.0 Hz); Chiral HPLC: Chiralcel OD-H 0.46×15 cm column, 15:85 EtOH/Heptane, 1.0 mL/min, 225 nm detection; Rt=7.37 min; >99% ee.

Provenance & Evidence