3-(2-fluorophenyl)prop-2-yn-1-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (102 mL, 1.18 mol, 1.2 equiv) in CH2Cl2 (3L) at −78° C. was slowly added DMSO (167 mL, 2.35 mol, 2.4 equiv) while keeping the reaction temperature below −59° C. The mixture was stirred for 10 min and treated with a solution of 3-(2-fluorophenyl)prop-2-yn-1-ol (147 g, 0.98 mol) in CH2Cl2 (100 mL), keeping the reaction temperature below −65° C. The resulting thick white slurry was stirred for 15 min, then treated with Et3N (682 mL, 4.90 mol, 5 equiv). After 10 min the reaction mixture was allowed to warm to 0° C. and treated with water (2 L). The organic layer was washed with water (3×1L), dried (Na2SO4) and concentrated under reduced pressure to afford 3-(2-fluorophenyl)prop-2-ynal (148 g, 100%) as a brown oil which was stored suspended in frozen benzene (0.5 L): 1H NMR (CDCl3) δ 7.03-7.14 (m, 2H), 7.37-7.52 (m, 2H), 9.36 (s, 1H); 13C NMR (CDCl3) δ 88.1, 92.4 (d, JC−F=2.4 Hz, 1C), 108.2 (d, JC−F=14.5 Hz, 1C), 115.9 (d, JC−F=19.6 Hz, 1C), 124.4 (d, JC−F=3.6 Hz, 1C), 133.3 (d, JC−F=8.5 Hz, 1C), 134.8 162.6 (d, JC−F=246.3 Hz, 1C), 176.4; GCMS m/z (rel abundance) 149 (MH+, 75%). at −78° C. the reaction temperature below −59° C the reaction temperature below −65° C The resulting thick white slurry was stirred for 15 min After 10 min the reaction mixture was allowed The organic layer was washed with water (3×1L) dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of 2-fluoro-iodobenzene (267 g, 1.2 mol) in Et3N (6L) was added propargyl alcohol (140 g, 2.5 mol, 2 equiv), followed by PdCl2(dppf) (6.1 g, 8.8 mmol, 0.007 equiv), Ph3P (12.5 g, 47.6 mmol, 0.038 equiv) and copper(I) iodide (12.6 g, 66.3 mmol, 0.053 equiv). The resulting mixture was heated at the reflux temperature for 17 h, allowed to cool to room temperature and filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure and purified by vacuum distillation to give 3-(2-fluorophenyl)prop-2-yn-1-ol (156.6 g, 87%) as a deep brown oil: bp 84° C./0.3 mmHg; TLC (CH2Cl2) Rf 0.44; 1H NMR (CDCl3) δ 2.46 (d, J=5.0 Hz, 1H), 4.45 (d, J=5.0 Hz, 1H), 6.94-7.02 (m, 2H), 7.17-7.23 (m, 1H), 7.31-7.37 (m, 1H); GCMS m/z (rel abundance) 151 (MH+, 75%). The resulting mixture was heated at the reflux temperature for 17 h filtered through a pad of Celite® The filtrate was concentrated under reduced pressure purified by vacuum distillation