Trifluoroacetic acid → 1,4-Dimethyl-6-hexadecyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-ol trifluoroacetic acid salt

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Reaction Conditions

Reaction Steps

To a solution of 15.0 mg (34.8 μmol) of 2c in 1 mL of CH2Cl2 was added 105 μL (105 μmol, 1.0 M in hexanes) of DIBAL-H at 78° C. The reaction mixture was stirred at 78° C. for 1 h and then 2 mL of sat aq sodium potassium tartrate was added slowly. The reaction mixture was slowly warmed to room temperature over a period of 30 min. The solution was extracted with three 5-mL portions of ethyl acetate. The combined organic layer was washed with brine, dried (MgSO4) and concentrated under diminished pressure to give the crude product as a yellow oil: silica gel TLC Rf 0.22 (1:9 MeOH/CH2Cl2). The residue was then dissolved in 1 mL of CH3CN and 1% aq TFA, frozen and lyophilized. The crude product was purified on a Prepex C8 reversed phase semi-preparative (250 mm×10 mm) HPLC column using a gradient of methanol and water. Linear gradients were employed using 1:4 methanol/water→4:1 methanol/water over a period of 20 min, and then 4:1 methanol/water→methanol over a period of 40 min, at a flow rate of 3.5 mL/min (monitoring at 260 nm). Fractions containing the desired product eluted at 37.5 min, and were collected, frozen, and lyophilized to give 1c as a light yellow solid: yield 11.0 mg (82%); 1H NMR (CD3CN) δ 0.89 (t, 3H, J=6.4 Hz), 1.27-1.36 (m, 28H), 1.55 (quint, 2H, J=7.2 Hz), 2.13 (s, 3H), 2.70 (t, 2H, J=8.0 Hz), 3.00 (t, 2H, J=8.4 Hz), 3.06 (s, 3H) and 3.73 (t, 2H, J=8.4 Hz); 13C NMR (CDCl3) δ 13.0, 13.4, 22.4, 24.4, 27.2, 28.6, 28.7, 28.99, 29.06, 29.07, 29.2, 29.30, 29.33, 29.36, 29.39, 29.39, 29.39, 31.6, 32.4, 53.1, 117.3, 126.2, 131.9, 140.2, 141.4 and 152.1; mass spectrum, m/z 388.3 (M)+ (theoretical 388.3); mass spectrum (APCI), m/z 389.3526 (M+H)+ (C25H45N2O requires 389.3532).

Provenance & Evidence