methyl 5-chloro-2-hydroxy-4-iodobenzoate

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of copper (I) iodide (1.1 g, 5.8 mmol) in triethylamine (32 mL) was degassed with nitrogen, treated with (trimethylsilyl)acetylene (4.5 mL, 32 mmol), degassed with nitrogen, and stirred at 20° C. for 10 minutes. The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), degassed with nitrogen, and stirred at 20° C. for 30 minutes. The reaction mixture was treated with methyl 5-chloro-2-hydroxy-4-iodobenzoate (5.0 g, 16 mmol), degassed with nitrogen, and stirred at 75° C. for 2 hours. The reaction mixture was filtered over celite, washed with ethyl acetate, and concentrated to a crude residue. Purification via flash column chromatography using ethyl acetate in hexanes (0%-20%) gave the desired product (4.31 g, 95%). LCMS for C13H16ClO3Si (M+H)+: m/z=283.1; Found: 282.9. degassed with nitrogen degassed with nitrogen stirred at 20° C. for 30 minutes degassed with nitrogen stirred at 75° C. for 2 hours The reaction mixture was filtered over celite washed with ethyl acetate concentrated to a crude residue Purification via flash column chromatography

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of copper (I) iodide (1.1 g, 5.8 mmol) in triethylamine (32 mL) was degassed with nitrogen, treated with (trimethylsilyl)acetylene (4.5 mL, 32 mmol), degassed with nitrogen, and stirred at 20° C. for 10 minutes. The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), degassed with nitrogen, and stirred at 20° C. for 30 minutes. The reaction mixture was treated with methyl 5-chloro-2-hydroxy-4-iodobenzoate (5.0 g, 16 mmol), degassed with nitrogen, and stirred at 75° C. for 2 hours. The reaction mixture was filtered over celite, washed with ethyl acetate, and concentrated to a crude residue. Purification via flash column chromatography using ethyl acetate in hexanes (0%-20%) gave the desired product (4.31 g, 95%). LCMS for C13H16ClO3Si (M+H)+: m/z=283.1; Found: 282.9. degassed with nitrogen degassed with nitrogen stirred at 20° C. for 30 minutes degassed with nitrogen stirred at 75° C. for 2 hours The reaction mixture was filtered over celite washed with ethyl acetate concentrated to a crude residue Purification via flash column chromatography

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

Procedure: A solution of methyl 2-hydroxy-4-iodobenzoate (50 g, 0.18 mol) [Aldrich, 652636] in acetic acid (360 mL) was treated with N-chlorosuccinimide (29 g, 0.22 mol) and heated at 100° C. for 1 hour. The reaction mixture was cooled until the internal temperature was 19° C. and then the solid that precipitated was filtered, washed with cold acetic acid, and air dried. The solid was diluted with toluene and concentrated (2×200 mL) to remove residual acetic acid to give 34.8 g of the desired product. The filtrate was concentrated, and the residue was purified by flash column chromatography using ethyl acetate in hexanes (0%-20%) to give an additional 8.6 g of desired product (total yield=43 g, 77%). LCMS for C8H7ClIO3 (M+H)+: m/z=312.9; Found: 313.0. The reaction mixture was cooled until the internal temperature was 19° C. the solid that precipitated was filtered washed with cold acetic acid, and air dried The solid was diluted with toluene concentrated (2×200 mL) to remove residual acetic acid

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 5-chloro-2-hydroxy-4-iodobenzoate (690 g, 2.2 mol), copper (I) iodide (4.2 g, 22 mmol) in triethylamine (5.6 L) was degassed with nitrogen for 5-10 minutes, treated with bis(triphenylphosphine)palladium(II) chloride (16 g, 22 mmol) and (trimethylsilyl)acetylene (470 mL, 3.3 mol), degassed with nitrogen for 2 minutes, and heated at 65° C. The heat was removed and the reaction temperature increased from 65 to 85° C. by itself. The temperature was dropped to 75° C. after 30 minutes with stirring. The reaction was cooled to room temperature, filtered over a pad of celite and rinsed with ethyl acetate (3 L). The filtrate was concentrated and dried on a high vacuum pump for 72 hours to give the desired product (650 g, quantitative) as a yellow solid. HPLC 91.3% pure @ 220 nm. LCMS for C13H16ClO3Si (M+H)+: m/z=283.1; Found: 282.8; 1H NMR (400 MHz, DMSO-d6): δ 10.5 (br s, 1 H), 7.76 (s, 1 H), 7.13 (s, 1 H), 3.85 (s, 3 H), 0.24 (s, 9 H). degassed with nitrogen for 2 minutes The heat was removed the reaction temperature increased from 65 to 85° C. by itself The temperature was dropped to 75° C. after 30 minutes The reaction was cooled to room temperature filtered over a pad of celite rinsed with ethyl acetate (3 L) The filtrate was concentrated dried on a high vacuum pump for 72 hours

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 2-hydroxy-4-iodobenzoate (470 g, 1.7 mol) in acetic acid (1.9 L) was treated with N-chlorosuccinimide (250 g, 1.9 mol) and heated at 100-110° C. for 1 h. The reaction mixture was cooled to room temperature and the solid that precipitated was filtered, rinsed with acetic acid (250 mL) and water (2×500 mL), and dried on the filter under vacuum overnight to give the desired product (370 g, 70%) as a yellow powder. HPLC 95.8% pure @ 220 nm. LCMS for C8H7ClIO3 (M+H)+: m/z=312.9; Found: 313.0; 1H NMR (300 MHz, DMSO-d6): δ 10.5 (s, 1 H), 7.75 (s, 1 H), 7.57 (s, 1 H), 3.83 (s, 3 H). The reaction mixture was cooled to room temperature the solid that precipitated was filtered rinsed with acetic acid (250 mL) and water (2×500 mL) dried on the filter under vacuum overnight

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

Procedure: To a mixture of methyl 5-chloro-2-hydroxy-4-iodobenzoate (5.1 g, 16 mmol) in acetic acid (50 mL) was added nitric acid (6.8 mL) at room temperature. The reaction was stirred at 60° C. for 90 min and then cooled and poured into ice water. The precipitate was collected by filtration, washed with water and air dried to give the desired product (5.15 g, 88%). cooled The precipitate was collected by filtration washed with water and air dried

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

Procedure: A mixture of methyl 2-hydroxy-4-iodobenzoate (10.0 g, 36.0 mmol, from Aldrich) and N-chlorosuccinimide (5.76 g, 43.2 mmol) in acetic acid (40 mL) was heated at 100° C. for 1 hour and then cooled to room temperature overnight. The precipitate was collected by filtration and washed with ethyl acetate and then air dried to give the desired product. In addition, the filtrate was concentrated to dryness and partitioned between water and ethyl acetate. The organic phase was separated, washed with brine, dried over sodium sulfate and concentrated to dryness. The residue was purified on silica gel, eluting with 0 to 20% ethyl acetate in hexane, to give additional desired product (total 9.03 g, 82%). LCMS calculated for C8H7ClIO3 (M+H)+: m/z=312.9; Found: 313.0. cooled to room temperature overnight The precipitate was collected by filtration washed with ethyl acetate air dried

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

Procedure: A solution of methyl 2-hydroxy-4-iodobenzoate (50 g, 0.18 mol) [Aldrich, 652636] in acetic acid (360 mL) was treated with N-chlorosuccinimide (29 g, 0.22 mol) and heated at 100° C. for 1 hour. The reaction mixture was cooled until the internal temperature was 19° C. and then the solid that precipitated was filtered, washed with cold acetic acid, and air dried. The solid was diluted with toluene and concentrated (2×200 mL) to remove residual acetic acid to give 34.8 g of the desired product. The filtrate was concentrated, and the residue was purified by flash column chromatography using ethyl acetate in hexanes (0%-20%) to give an additional 8.6 g of desired product (total yield=43 g, 77%). LCMS for C8H7ClIO3 (M+H)+: m/z=312.9; Found: 313.0. The reaction mixture was cooled until the internal temperature was 19° C. the solid that precipitated was filtered washed with cold acetic acid, and air dried The solid was diluted with toluene concentrated (2×200 mL) to remove residual acetic acid

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of copper (I) iodide (1.1 g, 5.8 mmol) in triethylamine (32 mL) was degassed with nitrogen, treated with (trimethylsilyl)acetylene (4.5 mL, 32 mmol), degassed with nitrogen, and stirred at 20° C. for 10 minutes. The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), degassed with nitrogen, and stirred at 20° C. for 30 minutes. The reaction mixture was treated with methyl 5-chloro-2-hydroxy-4-iodobenzoate (5.0 g, 16 mmol), degassed with nitrogen, and stirred at 75° C. for 2 hours. The reaction mixture was filtered over celite, washed with ethyl acetate, and concentrated to a crude residue. Purification via flash column chromatography using ethyl acetate in hexanes (0%-20%) gave the desired product (4.31 g, 95%). LCMS for C13H16ClO3Si (M+H)+: m/z=283.1; Found: 282.9. degassed with nitrogen degassed with nitrogen stirred at 20° C. for 30 minutes degassed with nitrogen stirred at 75° C. for 2 hours The reaction mixture was filtered over celite washed with ethyl acetate concentrated to a crude residue Purification via flash column chromatography

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of copper (I) iodide (1.1 g, 5.8 mmol) in triethylamine (32 mL) was degassed with nitrogen, treated with (trimethylsilyl)acetylene (4.5 mL, 32 mmol), degassed with nitrogen, and stirred at 20° C. for 10 minutes. The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), degassed with nitrogen, and stirred at 20° C. for 30 minutes. The reaction mixture was treated with methyl 5-chloro-2-hydroxy-4-iodobenzoate (5.0 g, 16 mmol), degassed with nitrogen, and stirred at 75° C. for 2 hours. The reaction mixture was filtered over celite, washed with ethyl acetate, and concentrated to a crude residue. Purification via flash column chromatography using ethyl acetate in hexanes (0%-20%) gave the desired product (4.31 g, 95%). LCMS for C13H16ClO3Si (M+H)+: m/z=283.1; Found: 282.9. degassed with nitrogen degassed with nitrogen stirred at 20° C. for 30 minutes degassed with nitrogen stirred at 75° C. for 2 hours The reaction mixture was filtered over celite washed with ethyl acetate concentrated to a crude residue Purification via flash column chromatography

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

Procedure: A solution of methyl 2-hydroxy-4-iodobenzoate (50 g, 0.18 mol) [Aldrich, 652636] in acetic acid (360 mL) was treated with N-chlorosuccinimide (29 g, 0.22 mol) and heated at 100° C. for 1 hour. The reaction mixture was cooled until the internal temperature was 19° C. and then the solid that precipitated was filtered, washed with cold acetic acid, and air dried. The solid was diluted with toluene and concentrated (2×200 mL) to remove residual acetic acid to give 34.8 g of the desired product. The filtrate was concentrated, and the residue was purified by flash column chromatography using ethyl acetate in hexanes (0%-20%) to give an additional 8.6 g of desired product (total yield=43 g, 77%). LCMS for C8H7ClIO3 (M+H)+: m/z=312.9; Found: 313.0. The reaction mixture was cooled until the internal temperature was 19° C. the solid that precipitated was filtered washed with cold acetic acid, and air dried The solid was diluted with toluene concentrated (2×200 mL) to remove residual acetic acid