Compound 10a

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InChIKey IRPXMRJUJPTCKR-UHFFFAOYSA-N

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a solution of the amino tributylstannane – SnAP reagent 1 (0.50 mmol, 1.00 equiv) in CH₂Cl₂ (2.5 mL) at rt was added the corresponding aldehyde (0.50 mmol, 1.00 equiv) and MS 4A (ca. 100 mg/mmol). The reaction mixture was stirred at rt for 2 h and filtered through a short layer of Celite (CH₂Cl₂ rinse). The filtrate was concentrated under reduced pressure to afford the pure imine.

Separately, to a solution of 2,6-lutidine (0.50 mmol, 1.00 equiv) in HFIP (2.0 mL) was added Cu(OTf)₂ (0.50 mmol, 1.00 equiv) and stirred at rt for 1 h, during which a homogeneous suspension was formed. A solution of the imine (0.50 mmol, 1.00 equiv) in CH₂Cl₂ (8.0 mL) was added in one portion and the resulting mixture was stirred at rt for 12 h. The reaction was quenched at rt with a mixture of sat aq NaHCO₃ (4 mL) and 10% aq NH₄OH (2 mL), and stirred vigorously for 15 min. The layers were separated and the aqueous layer was extracted with CH₂Cl₂ (3 x 5 mL). The combined organic layers were washed with H₂O (3 x 5 mL) and brine (10 mL), dried over Na₂SO₄, filtered, and concentrated. Purification by flash column chromatography (pentane/EtOAc 2:1 to 1:2) afforded 10a (105 mg, 86% yield) as colorless solid. IR (thin film): ν 3316, 2946, 1455, 1417, 1333, 1162, 1112, 1070, 763 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ 7.58 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 4.08-3.88 (m, 3H), 3.87-3.75 (m, 1H), 3.48 (dd, J = 12.4, 9.4 Hz, 1H), 3.22 (dt, J = 13.5, 4.9 Hz, 1H), 3.02 (dt, J = 13.5, 6.6 Hz, 1H), 1.93 (dt, J = 11.6, 6.6 Hz, 2H), 1.78 (br s, NH); ¹³C NMR (100 MHz, CDCl₃): δ 145.6, 129.8 (q, J_CF = 32.4 Hz), 127.6, 125.6 (q, J_CF = 3.7 Hz), 124.2 (q, J_CF = 273.6 Hz), 78.31, 70.2, 66.1, 46.3, 32.9; m.p. = 41–42 °C; ESI-HRMS calcd for C₁₂H₁₅F₃N₁O₁ [M + H] 246.1106, found 246.1105.