Triethylamine → Nipecotic Acid

Participants

Reaction Conditions

Reaction Steps

(S)-Nip.(S)-CSA 1.1. (1S)-(+)-10-Camphorsulfonic acid (11.62 g, 0.05 mol) was added to a stirred solution of racemic nipecotic acid (6.46 g, 0.05 mol) in acetone (100 mL). The solution was heated to reflux, and H2O (15 mL) was added until all solids dissolved. The solution was cooled to room temperature and allowed to stir overnight. The precipitate that formed was isolated by filtration and recrystallized three times with acetone/H2O (6/1, v/v) to afford 1.99 g (11% yield) of the desired product as a white solid: m.p. 221-223° C.; {a}D+25.3° (c 1.0, MeOH). Boc-(S)-Nip-OH 1.2. (S)-Nip.(S)-CSA (1.90 g, 5.3 mmol) was dissolved in methanol (12 mL). Triethylamine (2.2 mL, 15.8 mmol) and di-tert-butyl dicarbonate (1.38 g, 6.3 mmol) were added and the solution was stirred at 50° C. for 12 h. The solution was then concentrated, and the residue was dissolved in H2O. The aqueous solution was washed with diethyl ether, and the organic layer was discarded. The aqueous layer was acidified to pH 3 with 1 M HCl and extracted with CH2Cl2. The organic layer was dried over MgSO4 and concentrated to afford 1.24 g (quantitative yield) of the desired product as a white solid: m.p. 166-168° C.; FAB-MS m/z (M+Na+) calcd for C11H19NO4Na 252.3, obsd 252.5. Boc-(S)-Nip-OBn 1.3. Boc-(S)-Nip-OH (0.70 g, 3.1 mmol) was dissolved in N,N-dimethylformamide (DMF) (14 mL). Cs2CO3 (1.0 g, 3.1 mmol) and benzyl bromide (0.41 mL, 3.5 mmol) were added, and the solution was stirred at room temperature for 24 h. The solution was then concentrated, and the residue was dissolved in H2O. The aqueous solution was then extracted with CH2Cl2. The organic solution was dried over MgSO4 and concentrated to give an oil. The crude product was purified by column chromatography eluting with ethyl acetate/hexanes (1/3, v/v) to afford 0.81 g (82% yield) of the desired product as a white solid. 2. Oligomer Synthesis

Provenance & Evidence