1-bromo-4-iodo-2-methylbenzene

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2-bromo-5-iodotoluene (1.5 g), tert-butyl ((S)-5-oxopyrrolidin-3-yl)carbamate (2.7 g), copper iodide (95 mg), cesium fluoride (1.9 g), and N,N-dimethylethylenediamine (0.11 ml) in acetonitrile (20 ml) was stirred at 100° C. for 3 hours under a nitrogen atmosphere. After cooling, a saturated aqueous solution of ammonium chloride was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed with a 10% aqueous sodium thiosulfate solution and saturated saline in this order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain the title compound (1.8 g). After cooling followed by extraction with ethyl acetate The extract was washed with a 10% aqueous sodium thiosulfate solution and saturated saline in this order dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform-methanol)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-5-iodotoluene (500 mg, 1.68 mmol), (R)-4-hydroxy-pyrrolidinone (204 mg, 2.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (58.5 mg, 0.101 mmol), tris(dibenzylideneacetone)-dipalladium(0)-chloroform adduct (35.0 mg, 0.034 mmol) and cesium carbonate (769 mg, 2.36 mmol) in 1,4-dioxane (degassed, 5 ml) was stirred at 110° C. overnight in a nitrogen stream. The reaction mixture was treated with H2O and extracted with AcOEt (×2). The organic layers were combined and sequentially washed with H2O and saturated brine, and then dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (n-hexane/AcOEt) to give (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one as a pale brown solid (173 mg, 38%). extracted with AcOEt (×2) sequentially washed with H2O and saturated brine dried over Na2SO4 concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (n-hexane/AcOEt)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-5-iodotoluene (1.60 g, 5.40 mmol), 2-aminoethanol (0.49 mL, 8.14 mmol), CuI (53.3 mg, 0.28 mmol), L-proline (63.4 mg, 0.55 mmol) and K2CO3 (1.49 g, 10.8 mmol) in DMSO (3.24 mL) was stirred at 60° C. for 12 hours. The reaction mixture was cooled and then diluted with AcOEt, and the organic layer was sequentially washed with H2O and saturated brine. The organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/AcOEt=1/1) to give 2-(4-bromo-3-methyl-phenylamino)-ethanol as a brown solid (1.00 g, 81%). The reaction mixture was cooled the organic layer was sequentially washed with H2O and saturated brine The organic layer was dried over Na2SO4 concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (hexane/AcOEt=1/1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2-bromo-5-iodotoluene (1.5 g), tert-butyl ((S)-5-oxopyrrolidin-3-yl)carbamate (2.7 g), copper iodide (95 mg), cesium fluoride (1.9 g), and N,N-dimethylethylenediamine (0.11 ml) in acetonitrile (20 ml) was stirred at 100° C. for 3 hours under a nitrogen atmosphere. After cooling, a saturated aqueous solution of ammonium chloride was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed with a 10% aqueous sodium thiosulfate solution and saturated saline in this order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain the title compound (1.8 g). After cooling followed by extraction with ethyl acetate The extract was washed with a 10% aqueous sodium thiosulfate solution and saturated saline in this order dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform-methanol)