1-[1-(furan-3-yl)ethyl]-1-hydroxyurea

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-1-(fur-3-yl)ethyl-N-hydroxyurea (1.00 g, 5.9 mmol), prepared as described in U.S. Pat. No. 5,112,848, in CH2Cl2 (25 mL) was added naproxen (135 g, 5.9 mmol) followed by dicyclohexylcarbodiimide (1.34 g, 6.49 mmol), and a crystal of 4-N,N-dimethylaminopyridine. The reaction was stirred for 18 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (ether), followed by crystallization in ethyl acetate/hexanes to give N-[(S)-2-(6-methoxynaphth-2-yl)propionyloxy]-N-[1-(fur-3-yl)ethyl]urea (1.54 g). m.p. 128.5°-134° C. 1H NMR (300 MHz, DMSO-d6, mixture of diastereomers) δ 0.72 and 1.12 (bm, 3H), 1.48 (bm, 3H), 3.87 (s, 3H), 4.13 (bm, 1H), 5.14 (bm, 1H), 6.79 and 6.94 (bs, 2H), 7.16 (m, 2H), 7.29-7.46 (m, 3H), 7.69-7.86 (m, 3H). MS (DCI/NH3) m/e 383 (M+H)+. Analysis calc'd for C21H22N2O5 : C, 65.95; H, 5.80; N, 7.33. Found: C, 65.39; H; 5.80; N, 7.26. The reaction mixture was filtered through Celite the filtrate was concentrated in vacuo The residue was purified by chromatography on silica gel (ether) followed by crystallization in ethyl acetate/hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-1-(fur-3-yl)ethyl-N-hydroxyurea (1.00 g, 5.9 mmol), prepared as described in U.S. Pat. No. 5,112,848, in CH2Cl2 (25 mL) was added naproxen (135 g, 5.9 mmol) followed by dicyclohexylcarbodiimide (1.34 g, 6.49 mmol), and a crystal of 4-N,N-dimethylaminopyridine. The reaction was stirred for 18 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (ether), followed by crystallization in ethyl acetate/hexanes to give N-[(S)-2-(6-methoxynaphth-2-yl)propionyloxy]-N-[1-(fur-3-yl)ethyl]urea (1.54 g). m.p. 128.5°-134° C. 1H NMR (300 MHz, DMSO-d6, mixture of diastereomers) δ 0.72 and 1.12 (bm, 3H), 1.48 (bm, 3H), 3.87 (s, 3H), 4.13 (bm, 1H), 5.14 (bm, 1H), 6.79 and 6.94 (bs, 2H), 7.16 (m, 2H), 7.29-7.46 (m, 3H), 7.69-7.86 (m, 3H). MS (DCI/NH3) m/e 383 (M+H)+. Analysis calc'd for C21H22N2O5 : C, 65.95; H, 5.80; N, 7.33. Found: C, 65.39; H; 5.80; N, 7.26. The reaction mixture was filtered through Celite the filtrate was concentrated in vacuo The residue was purified by chromatography on silica gel (ether) followed by crystallization in ethyl acetate/hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-1-(fur-3-yl)ethyl-N-hydroxyurea (1.00 g, 5.9 mmol), prepared as described in U.S. Pat. No. 5,112,848, in CH2Cl2 (25 mL) was added naproxen (135 g, 5.9 mmol) followed by dicyclohexylcarbodiimide (1.34 g, 6.49 mmol), and a crystal of 4-N,N-dimethylaminopyridine. The reaction was stirred for 18 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (ether), followed by crystallization in ethyl acetate/hexanes to give N-[(S)-2-(6-methoxynaphth-2-yl)propionyloxy]-N-[1-(fur-3-yl)ethyl]urea (1.54 g). m.p. 128.5°-134° C. 1H NMR (300 MHz, DMSO-d6, mixture of diastereomers) δ 0.72 and 1.12 (bm, 3H), 1.48 (bm, 3H), 3.87 (s, 3H), 4.13 (bm, 1H), 5.14 (bm, 1H), 6.79 and 6.94 (bs, 2H), 7.16 (m, 2H), 7.29-7.46 (m, 3H), 7.69-7.86 (m, 3H). MS (DCI/NH3) m/e 383 (M+H)+. Analysis calc'd for C21H22N2O5 : C, 65.95; H, 5.80; N, 7.33. Found: C, 65.39; H; 5.80; N, 7.26. The reaction mixture was filtered through Celite the filtrate was concentrated in vacuo The residue was purified by chromatography on silica gel (ether) followed by crystallization in ethyl acetate/hexanes