3-iodo-4-methylphenol

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

Procedure: Following the General Procedure of Description 15 (Part A), zinc dust (Zn) (392 mg, 6.0 mmol) is activated with elemental iodine (I2) (38 mg, 0.15 mmol, 15 mol-%) and trimethyl silylchloride (MeSiCl, TMSCl) (19 μL, 16 mg, 0.15 mmol, 15 mol-%) in degassed anhydrous N,N-dimethylformamide (DMF) (3 mL). The zinc insertion product is prepared from tert-butyl(3S)-3-(tert-butoxycarbonylamino)-4-iodo-butanoate (6c) (385 mg, 1.0 mmol) in the presence of additional I2 (38 mg, 0.15 mmol, 15 mol-%) and TMSCl (19 μL, 16 mg, 0.15 mmol, 15 mol-%). Following the General Procedure of Description 15 (Part B), the zinc insertion product of (6c) is used in situ to cross couple with commercial 3-iodo-4-methyl-phenol (234 mg, 1.0 mmol) in the presence of tris(benzylideneacetone)dipalladium (Pd2(dba)3) (23 mg, 0.025 mmol, 2.5 mol-%) and tris(o-tolyl)phosphine (P(o-tol)3) (30 mg, 0.10 mmol, 10 mol-%) in anhydrous degassed DMF (3 mL). Filtration, aqueous work-up, and purification by silica gel column chromatography furnish the title compound (19a). in anhydrous degassed DMF (3 mL) Filtration, aqueous work-up, and purification by silica gel column chromatography

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

Procedure: A mixture of 3-iodo-4-methylphenol 1-1 (500 mg, 2.14 mmol), tert-butyldimethylchlorosilane (387 mg, 2.57 mmol) and imidazole (175 mg, 2.57 mmol) in 11 mL of DMF was stirred at rt for 16 h, and then diluted with diethylether, washed with water, brine, dried (MgSO4) and evaporated. The residue was subjected to MPLC on a 40 g column of SiO2 eluting with hexanes to provide 5-tert-butyldimethylsilyloxy-2-methylphenyliodide 1-2 as an oil. 1H NMR (300 MHz, DMSO-d6): δ 0.17 (s, 6H), 0.93 (s, 9H), 2.29 (s, 3H), 6.81 (dd, 1H, J=8, 2 Hz), 7.20 (d, 1H, J=8 Hz), 7.28 (d, 1H, J=2 Hz). washed with water, brine dried (MgSO4) evaporated

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

Procedure: A mixture of 8 mL of concentrated H2SO4, 12 mL of water, 3-iodo-4-methylaniline (5.00 g, 21.5 mmol) and 20 g of ice was stirred under ice-bath cooling until a paste resulted. To this paste was added slowly an ice-cold solution of NaNO2 (1.55 g, 22.4 mmol) in 3.5 mL of water and the resulting mixture stirred for 20 minutes while maintaining the temperature at <5° C. The resulting suspension was slowly added to a mixture of 26 mL of concentrated H2SO4 and 24 mL of water preheated to 80° C. This mixture was stirred at 80° C. for 15 min, then chilled in an ice-bath and poured onto 200 g of ice. The resulting mixture was extracted with 100 mL of EtOAc, and the organic extract washed with water, brine, dried (MgSO4) and evaporated to give a residue. The residue was adsorbed onto 15 g of SiO2 from CH2Cl2, loaded into a precolumn and subjected to MPLC through a 120 g column of SiO2 eluting with 5% EtOAc in hexanes (10 min) and then 10% EtOAc (20 min) to provide 3-iodo-4-methylphenol 1-1 as an oil. 1H NMR (300 MHz, DMSO-d6): δ 2.25 (s, 3H), 6.71 (dd, 1H, J=8, 2 Hz), 7.11 (d, 1H, J=8 Hz), 7.23 (d, 1H, J=2 Hz), 9.51 (s, 1H); LC-MS: calculated for C7H7IO 234.0, observed m/e 234.6 (M+H)+. cooling until a paste resulted the resulting mixture stirred for 20 minutes while maintaining the temperature at <5° C preheated to 80° C This mixture was stirred at 80° C. for 15 min chilled in an ice-bath The resulting mixture was extracted with 100 mL of EtOAc the organic extract washed with water, brine dried (MgSO4) evaporated to give a residue

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

Procedure: Following the General Procedure of Description 15 (Part A), zinc dust (Zn) (392 mg, 6.0 mmol) is activated with elemental iodine (I2) (38 mg, 0.15 mmol, 15 mol-%) and trimethyl silylchloride (MeSiCl, TMSCl) (19 μL, 16 mg, 0.15 mmol, 15 mol-%) in degassed anhydrous N,N-dimethylformamide (DMF) (3 mL). The zinc insertion product is prepared from tert-butyl(3S)-3-(tert-butoxycarbonylamino)-4-iodo-butanoate (6c) (385 mg, 1.0 mmol) in the presence of additional I2 (38 mg, 0.15 mmol, 15 mol-%) and TMSCl (19 μL, 16 mg, 0.15 mmol, 15 mol-%). Following the General Procedure of Description 15 (Part B), the zinc insertion product of (6c) is used in situ to cross couple with commercial 3-iodo-4-methyl-phenol (234 mg, 1.0 mmol) in the presence of tris(benzylideneacetone)dipalladium (Pd2(dba)3) (23 mg, 0.025 mmol, 2.5 mol-%) and tris(o-tolyl)phosphine (P(o-tol)3) (30 mg, 0.10 mmol, 10 mol-%) in anhydrous degassed DMF (3 mL). Filtration, aqueous work-up, and purification by silica gel column chromatography furnish the title compound (19a). in anhydrous degassed DMF (3 mL) Filtration, aqueous work-up, and purification by silica gel column chromatography