1-chloro-2-iodo-4-(trifluoromethyl)benzene

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

Procedure: A mixture of 4-chloro-3-iodobenzotrifluoride (10.0 g), copper(I) iodide (124 mg), triphenylphosphine (428 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (675 mg), propargyl alcohol (2.12 ml), diisopropylethylamine (22.6 ml) and tetrahydrofuran (180 ml) was stirred at room temperature for 15 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20) to give the object product (7.63 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20)

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

Procedure: Beginning with 4-chloro-3-iodobenzotrifluoride and 1-propyl-4-piperidone, the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35). the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35)

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

Procedure: Beginning with 4-chloro-3-iodobenzotrifluoride and 1-propyl-4-piperidone, the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35). the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35)

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

Procedure: Beginning with 4-chloro-3-iodobenzotrifluoride and 1-propyl-4-piperidone, the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35). the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35)

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

Procedure: This material was prepared in analogy to example 148 step F) from 8-(2-chloro-benzenesulfonyl)-2,8-diaza-spiro[4.5]decan-1-one and 1-chloro-2-iodo-4-trifluoromethyl-benzene. White solid. MS (ESI): 507.0 MH+).

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

Procedure: The title compound was prepared in analogy to Example 5 starting from 1-chloro-2-iodo-4-trifluoromethyl-benzene (commercially available) and 3-{[phenyl-(3-phenyl propynoyl)-amino]-methyl}-benzoic acid methyl ester. 1H NMR (CDCl3, 300 MHz) δppm 8.01 (s, 1H), 7.93 (d, 1H), 7.63-7.67 (m, 2H), 7.33-7.52 (m, 7H), 7.10 (t, 1H), 6.64-6.71 (m, 2H), 5.98 (d, 1H), 4.87-5.04 (m, 2H), 3.91 (s, 3H).

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-chloro-3-iodobenzotrifluoride (63.3 g), 1-fluoro-2-fluoromethyl-3-butyn-2-ol (28.8 g), triethylamine (26.2 g), cuprous iodide (0.38 g), bis(triphenylphosphine)palladium chloride (1.40 g) and N,N-dimethylformamide (100 ml) was stirred under a nitrogen atmosphere under heating at 80° C. for 1.5 hours. To the reaction mixture, 2 N HCl and a hexane/ethyl acetate mixed solvent (3/1) were added and the insoluble matter was filtered off with Celite; following extraction with a hexane/ethyl acetate mixed solvent (3/1), the resulting organic layers were combined, washed with a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate and concentrated under reduced pressure; the resulting residue was purified by distillation to give 4-(2-chloro-5-trifluoromethylphenyl)-1-fluoro-2-fluoromethyl-3-butyn-2-ol (44.5 g) having a boiling point of 105-107° C./1 mmHg. the insoluble matter was filtered off with Celite extraction with a hexane/ethyl acetate mixed solvent (3/1) washed with a saturated aqueous solution of sodium chloride dried with anhydrous sodium sulfate concentrated under reduced pressure the resulting residue was purified by distillation

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

Procedure: A mixture of 4-chloro-3-iodobenzotrifluoride (10.0 g), copper(I) iodide (124 mg), triphenylphosphine (428 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (675 mg), propargyl alcohol (2.12 ml), diisopropylethylamine (22.6 ml) and tetrahydrofuran (180 ml) was stirred at room temperature for 15 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20) to give the object product (7.63 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20)

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

Procedure: Beginning with 4-chloro-3-iodobenzotrifluoride and 1-propyl-4-piperidone, the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35). the titled compound was recovered by the procedure described in Preparation 4, MS m/z (rel. intensity, 70 eV)) 321 (M+, 8), 294 (38), 292, (bp), 274 (52), 56 (35)