1,1,1-trifluorobut-3-en-2-ol

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

Procedure: (2S, 4S)-1-N-Dodecyl-4-(4-iodophenoxy)pyrrolidine-2-carboxylic acid, methyl ester (800 mg, 1.55 mmol) and 4,4,4-trifluorobut-1-en-3-ol (complex with 1 tetrahydrofuran, 620 mg, 3.1 mmol) were reacted by the general procedure as described in the preparation of 4-[N-dodecyl-N-2-[4-(E)-[3-hydroxy-4,4,4-trifluorobut-1-en-1-yl]phenoxy]ethylamino]butanoic acid, ethyl ester and afforded the title compound (575 mg, 72%) as a colorless oil [[a]D=−28.7° (c 0.8, CHCl3)] and (2S, 4S)-1-N-dodecyl-4-[4-(3-oxo-4,4,4-trifluorobut-1-yl)phenoxy]pyrrolidine-2-carboxylic acid, methyl ester (68 mg, 9%) as a pale yellow oil.

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

Procedure: [N-Dodecyl-N-[2-[4-iodophenoxy]ethyl]amino]propanoic acid, ethyl ester (0.95 g, 1.79 mmol) and 4,4,4-trifluorobut-1-en-3-ol (complex with 0.7 THF, 0.95 g, 5.4 mmol) were reacted by the general procedure as described in the preparation of 4-[N-dodecyl-N-2-[4-(E)-[3-hydroxy-4,4,4-trifluorobut-1-en-1-yl]phenoxy]ethylamino]butanoic acid, ethyl ester (Example 48) and afforded the title compound (0.633 g, 76%) as a colorless oil.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[N-dodecyl-N-2-[4-iodophenoxy]ethylamino]butanoic acid, ethyl ester (4.5 g, 8.3 mmol) and 4,4,4-trifluorobut-1-en-3-ol (Pegolotti, J. A. and Young, W. G. J. Amer. Chem. Soc., 1961, 83, 3251) (complex with 1 tetrahydrofuran, 3.3 g, 16.6 mmol) in N, N-dimethylformamide (17 ml) were added sodium bicarbonate (1.75 g, 20.8 mmol), tetrabutyl ammonium chloride hydrate (2.5 g, 8.32 mmol) and palladium (II) acetate (56 mg, 0.25 mmol). The resulting mixture was stirred at 50° C. for 24 h, and then diluted with ethyl acetate (300 ml), washed with brine (100 ml), sat. aq. sodium thiosulfate (2×100 ml), brine (2×100 ml), dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (Hexane/ethyl acetate 4:1 to 2:1) to afford the title compound (3.5 g, 78%) as a colorless oil and 0.3 g (6.6%) of 4-[N-Dodecyl-N-[2-[4-(4,4,4-trifluoro-3-oxo-but-1-yl)phenoxy]ethyl]amino]butanoic acid, ethyl ester. washed with brine (100 ml), sat. aq. sodium thiosulfate (2×100 ml), brine (2×100 ml) dried over sodium sulfate concentrated in vacuo The residue was chromatographed on silica gel (Hexane/ethyl acetate 4:1 to 2:1)

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

Procedure: (2S, 4S)-1-N-Dodecyl-4-(4-iodophenoxy)pyrrolidine-2-carboxylic acid, methyl ester (800 mg, 1.55 mmol) and 4,4,4-trifluorobut-1-en-3-ol (complex with 1 tetrahydrofuran, 620 mg, 3.1 mmol) were reacted by the general procedure as described in the preparation of 4-[N-dodecyl-N-2-[4-(E)-[3-hydroxy-4,4,4-trifluorobut-1-en-1-yl]phenoxy]ethylamino]butanoic acid, ethyl ester and afforded the title compound (575 mg, 72%) as a colorless oil [[a]D=−28.7° (c 0.8, CHCl3)] and (2S, 4S)-1-N-dodecyl-4-[4-(3-oxo-4,4,4-trifluorobut-1-yl)phenoxy]pyrrolidine-2-carboxylic acid, methyl ester (68 mg, 9%) as a pale yellow oil.

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

Procedure: [N-Dodecyl-N-[2-[4-iodophenoxy]ethyl]amino]propanoic acid, ethyl ester (0.95 g, 1.79 mmol) and 4,4,4-trifluorobut-1-en-3-ol (complex with 0.7 THF, 0.95 g, 5.4 mmol) were reacted by the general procedure as described in the preparation of 4-[N-dodecyl-N-2-[4-(E)-[3-hydroxy-4,4,4-trifluorobut-1-en-1-yl]phenoxy]ethylamino]butanoic acid, ethyl ester (Example 48) and afforded the title compound (0.633 g, 76%) as a colorless oil.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-[N-dodecyl-N-2-[4-iodophenoxy]ethylamino]butanoic acid, ethyl ester (4.5 g, 8.3 mmol) and 4,4,4-trifluorobut-1-en-3-ol (Pegolotti, J. A. and Young, W. G. J. Amer. Chem. Soc., 1961, 83, 3251) (complex with 1 tetrahydrofuran, 3.3 g, 16.6 mmol) in N, N-dimethylformamide (17 ml) were added sodium bicarbonate (1.75 g, 20.8 mmol), tetrabutyl ammonium chloride hydrate (2.5 g, 8.32 mmol) and palladium (II) acetate (56 mg, 0.25 mmol). The resulting mixture was stirred at 50° C. for 24 h, and then diluted with ethyl acetate (300 ml), washed with brine (100 ml), sat. aq. sodium thiosulfate (2×100 ml), brine (2×100 ml), dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (Hexane/ethyl acetate 4:1 to 2:1) to afford the title compound (3.5 g, 78%) as a colorless oil and 0.3 g (6.6%) of 4-[N-Dodecyl-N-[2-[4-(4,4,4-trifluoro-3-oxo-but-1-yl)phenoxy]ethyl]amino]butanoic acid, ethyl ester. washed with brine (100 ml), sat. aq. sodium thiosulfate (2×100 ml), brine (2×100 ml) dried over sodium sulfate concentrated in vacuo The residue was chromatographed on silica gel (Hexane/ethyl acetate 4:1 to 2:1)