1255206-67-7|5-Bromo-4-methylisobenzofuran-1(3H)-one| Ambeed

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1
[ 1255206-67-7 ]
[ 24850-33-7 ]
[ 1255208-99-1 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium chloride;tetrakis(triphenylphosphine) palladium(0); In toluene;Inert atmosphere; Reflux;Product distribution / selectivity;	A mixture of 5-bromo-4-methyl-2-benzofuran-l(3H)-one (980 mg, 4.3 mmol), allyl-tributyl- stannane (1.7 g, 5.2 mmol), LiCl (550 mg, 12.9 mmol) and Pd(PPh3)4 (0.1 g) in anhydrous toluene was stirred at reflux under N2 overnight. The solvent was removed under reduced pressure, and the residue was purified with silica gel column chromatography to give the product 4-methyl-5-prop-2-en- 1 -yl-2-benzofuran- 1 (3/i)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	Step A: 4-methyl-5-prop-2-en-l-yl-2-benzofuran-l(3H)-one:To a flask charged with 5-Bromo-4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.41 mmol) and a stir bar was added Allyl tri-n-butyltin (0.655 ml, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was purified by silica gel chromatography to give the title compound.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	Step A: 4-Methyl-5-prop-2-en-l-yl-2-benzofuran-l(3H)-one To a flask charged with 5-bromo-4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.4 mmol) and a stir bar was added allyl tri-n-butyltin (0.66 mL, 2.1 mmol), Pd(PPh3)4 (240 mg, 0.21 mmol), lithium chloride (180 mg, 4.2 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The reaction mixture was diluted with DCM, adsorbed onto silica gel, and purified by silica gel chromatography to provide 4-methyl-5- prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.

	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with 5-bromo- 4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n- butyltin (0.655 mL, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4-methyl-5- prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with 5-bromo- 4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n- butyltin (0.655 mL, 2.1 1 mmol), Pd(PPh3)4 (244 mg, 0.21 1 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4- methyl-5-prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with 5-bromo-4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.4 mmol) and a stir bar was added allyl tri-n-butyltin (0.66 mL, 2.1 mmol), Pd(PPh3)4 (240 mg, 0.21 mmol), lithium chloride (180 mg, 4.2 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The reaction mixture was diluted with DCM, adsorbed onto silica gel, and purified by silica gel chromatography to provide 4-methyl-5- prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with 5-bromo- 4-methyl-2-benzofuran- 1 (3H)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-nbutyltin (0.655 mL, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (1?79 mg,4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then washeated at reflux for 4 hours. The product was separated by silica gel chromatography to giye 4- methyl-5-prop-2-en-1-yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	Step A: 4-methyl-5-prop-2-en-i-yl-2-benzofuran-i(3H)-one: To a flask charged with 5-bromo-4-methyl-2-benzofuran- 1 (311)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tn-nbutyltin (0.655 mL, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4- methyl-S -prop-2-en- 1 -yl-2-benzofuran- 1 (311)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with 5-bromo-4-methyl-2-benzofuran-i(311)-one (320 mg, 1.409 mmol) andstir bar was added allyl tri-n-butyltin (0.655 ml, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol),lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gelchromatography to give 4-methyl-S -prop-2-en- 1 -yl-2-benzofuran- 1(311)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with 5-bromo- 4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n- butyltin (0.655 mL, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 h. The product was separated by silica gel chromatography to give 4- methyl-5-prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	Step A: 4-Methyl-5-prop-2-en-l-yl-2-benzofuran-l(3H)-one: To a flask charged with 5-bromo- 4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n- butyltin (0.655 mL, 2.1 1 mmol), Pd(PPh3)4 (244 mg, 0.21 1 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4- methyl-5-prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	Step A: 4-Methyl-5-prop-2-en-l-yl-2-benzofuran-l(3H)-one: To a flask charged with 5-bromo- 4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n- butyltin (0.655 mL, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.21 1 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4- methyl-5-prop-2-en- 1 -yl-2-benzofuran- 1 (3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	To a flask charged with <strong>[1255206-67-7]5-bromo-4-methyl-2-benzofuran-1(3H)-one</strong> (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n-butyltin (0.655 ml, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4-methyl-5-prop-2-en-1-yl-2-benzofuran-1(3H)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Reflux; Inert atmosphere;	Step A: 4-Methyl-5-prop-2-en-i-yl-2-benzofuran-i(3H)-one: To a flask charged with 5-bromo-4- methyl-2-benzofuran- 1(311)-one (320 mg, 1.409 mmol) and a stir bar was added allyl tri-n-butyltin (0.655 mL, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg,4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was separated by silica gel chromatography to give 4- methyl-S -prop-2-en- 1 -yl-2-benzofuran- 1 (311)-one.
	With tetrakis(triphenylphosphine) palladium(0); lithium chloride; In toluene; for 4h;Inert atmosphere; Reflux;	Step A: 4-methyl-5-prop-2-en-l-yl-2-benzofuran-l(3H)-one:To a flask charged with 5-Bromo-4-methyl-2-benzofuran-l(3H)-one (320 mg, 1.41 mmol) and a stir bar was added Allyl tri-n-butyltin (0.655 ml, 2.11 mmol), Pd(PPh3)4 (244 mg, 0.211 mmol), lithium chloride (179 mg, 4.23 mmol), and toluene (15 mL). The reaction was purged with nitrogen 2 times then was heated at reflux for 4 hours. The product was purified by silica gel chromatography to give the title compound.

Reference： [1]Patent: WO2010/129379,2010,A1 .Location in patent: Page/Page column 50
[2]Patent: WO2013/62900,2013,A1 .Location in patent: Page/Page column 36
[3]Patent: WO2013/39802,2013,A1 .Location in patent: Page/Page column 66; 67
[4]Patent: WO2014/15495,2014,A1 .Location in patent: Page/Page column 25
[5]Patent: WO2014/18764,2014,A1 .Location in patent: Page/Page column 28
[6]Patent: WO2014/85210,2014,A1 .Location in patent: Page/Page column 25
[7]Patent: WO2014/126944,2014,A2 .Location in patent: Page/Page column 30; 36
[8]Patent: WO2015/17305,2015,A1 .Location in patent: Page/Page column 40
[9]Patent: WO2015/65866,2015,A1 .Location in patent: Page/Page column 27
[10]Patent: WO2015/95097,2015,A2 .Location in patent: Page/Page column 27
[11]Patent: WO2015/96035,2015,A1 .Location in patent: Page/Page column 40; 41
[12]Patent: WO2015/100147,2015,A1 .Location in patent: Page/Page column 41A
[13]Patent: EP2632465,2015,B1 .Location in patent: Paragraph 0084
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[15]Patent: WO2013/62892,2013,A1 .Location in patent: Page/Page column 52; 53

2
[ 201230-82-2 ]
[ 83647-43-2 ]
[ 1255206-67-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a IM TFA solution of Thallium Trifiuoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4- methyl-2-benzofuran-l (3H)-one. 1H-NMR (500 MHz, CDCl3) delta ppm 7.71 (d, J= 8.0 Hz, IH), 7.58 (d, J= 8.0 Hz, IH), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M trifluoroacetic acid solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 minutes to ensure complete removal of TFA. To the residue was then added palladium (II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a Celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran-l(3H)-one. ?-NMR (500 MHz, CDC13) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1 M trifluoroacetic acid solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at room temperature overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 minutes to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a Celite diatomaceous earth pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2- benzofuran- 1 (3H)-one.1H-NMR (500 MHz, CDC13) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).

		Step B: 5-Bromo-4-methyl-2-benzofuran-U3H)-one: To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of ThalliumTrifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at RT. Analysis by LC showed a formation of product within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The solution was filtered through a celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to provide the title compound
		Step B: 5-Bromo-4-methyl-2-benzofuran-l(3H)-one: To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of ThalliumTrifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at RT. Analysis by LC showed a formation of product within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The solution was filtered through a celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to provide the title compound
		To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The solution was filtered through a Celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford the title compound: 1H-NMR (500 MHz, CDCI3) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		Step B: 5-Bromo-4-methyl-2-benzofuran-l(3H)-one To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M trifluoroacetic acid solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a diatomaceous earth pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDC13) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M trifluoroacetic acid solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at room temperature overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 minutes to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a Celite diatomaceous earth pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2- benzofuran-1 (3H)-one. -N R (500 MHz, CDC13) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2,37 (s, 3H).
		INTERMEDIATE 2 5-bromo-4-methyl-2-benzofuran-1 (3H)-one; Step B; To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution ofthalliumtrifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residuewas pumped under high vacuum for 30 min to ensure complete removal of TF A. To the residuewas then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushedwith CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. Thesolution was filtered through a Celite pad, washed with EtOAc, adsorbed onto silica and purifiedby silica gel chromatography to afford the title compound: 1H-NMR (500 MHz, CDCh) 8 ppm7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound. 1H-NMR (500 MHz, CDC13) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound. 1H-NMR (500 MHz, CDCI3) delta ppm 7.71 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4- methyl-2-benzofuran-l(3H)-one. -NMR (500 MHz, CDC13) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		Step B: 5-bromo-4-methyl-2-benzofuran-l(3H)-one: To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residuewas pumped under high vacuum for 30 mm to ensure complete removal of TEA. To the residue was then added Palladium(fl) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. Thesolution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford the title compound: ?H-NMR (500 MHz, CDC13) 6 ppm 7.71 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a fiask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a lM TFA solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT oyernight. Analysis by TLC showed no starting material remaining. The solyent was remoyed under yacuum, and the residuewas pumped under high yacuum for 30 min to ensure complete remoyal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The blaeksolution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound. 1H-NMR (500 MHz, CDC13)ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		Step B: 5-bromo-4-methyl-2-benzofuran-1(3H)-one: To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of thalliumtrifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 mm to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran-1(3H)-one. ?H-NMR (500 MHz, CDC13) oe ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H),2.37 (s, 3H).
		: To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of ThalliumTrifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 mm to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g,59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5 -bromo-4-methyl-2-benzofuran- 1 (311)-one.1H-NMR (500 MHz, CDC13) oe ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J 8.0 Hz, 1H), 5.25 (s,2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2- metiiyiplienyijmethanol (6.0 g, 30 mmol) was added a 1 M TFA solutio of Thallium Trifiuoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT 16 h. Analysis by TLC showed no starting material remaining. The solve t was removed under vacuum, and the residue was pumped under high vacuum for 30 mm to ensure complete removal of TF A. To the residue was then added Palladiimi( ll) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at rt. Analysis by LC showed a big product spot within 2 h. To this solution was added ethyl acetate to precipitate the salts. The black solutio was filtered through a ('elite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography. 5-bromo~4-methyl-2~benzofuran~ 1 (3H)-one. ]H-NMR (500 MHz, CDCI3) delta ppm 7.71 (d, J = 8.0 Hz, i i l 7.58(d, J = 8.0 Hz, i i l 5.25 (s, 21 1 ). 2.37 (s, M l }.
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirredRT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 mm to ensurecomplete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was addeda 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred atRT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 mm to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), andMeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hr. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford the title compound. ?H-NMR (500 MHz, CDC13) oe ppm 7.71 (d, J 8.0 Hz, 1H), 7.58 (d, J 8.0 Hz,1H), 5.25 (s, 2H), 2.37 (s, 3H).
		Step B: 5-bromo-4-methyl-2-benzofuran-l(3H)-one: To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. After two hours, to this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound.
		Step B: 5-bromo-4-methyl-2-benzofuran-l(3H)-one: To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. After two hours, to this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound.
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran-1(3H)-one. 1H-NMR (500 MHz, CDCl3) delta ppm 7.71 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl) methanol (6.0 g, 30 mmol) was added a 1M TFA solution of thallium trifluoroacetate (16.2 g, 29.8 mmol) . The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added palladium (II) chloride (529 mg, 2.98 mmol) , lithium chloride (2.53 g, 59.7 mmol) , magnesium oxide (2.41 g, 59.7 mmol) , and MeOH (150 mL) . The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through apad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran-1 (3H) -one. 1H NMR (500 MHz, CDCl3) delta ppm 7.71 (d, J 8.0 Hz, 1H) , 7.58 (d, J 8.0 Hz, 1H) , 5.25 (s, 2H) , 2.37 (s, 3H).
		To a flask charged with (3-bromo-2- methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at rt overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound. 1H-NMR (500 MHz, CDCI3) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl)methanol(6.0 g, 30 mmol) was added a 1M TFA solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture wasstirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed undervacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To theresidue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magne-sium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under COat room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethylacetate to precipitate the salts. The solution was filtered through a Celite pad, washed with EtOAc, adsorbed ontosilica and purified by silica gel chromatography to afford the title compound: 1H-NMR (500 MHz, CDCl3) delta ppm 7.71(d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		To a flask charged with (3-bromo-2-methylphenyl)metha- nol (6.0 g, 30 mmol) was added a 1M trifluoroacetic acidsolution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at room temperature overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 minutes to ensure complete removal of TFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mE). The reaction was flushed with CO twice, and kept under CO at room temperature.Analysis by EC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a Celite diatomaceous earth pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran- 1 (3H)-one.?H-NMR (500 MHz, CDC13) oe ppm 7.71 (d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).
		[0129] To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M trifluoroaceticacid solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent wasremoved under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal ofTFA. To the residue was then added palladium(II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol),magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mL). The reaction was flushed with CO twice, and kept underCO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethylacetate to precipitate the salts. The black solution was filtered through a diatomaceous earth pad, washed with EtOAc,adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran- I(3H)-one. 1HNMR(500 MHz, CDCl3) delta ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H)

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3
[ 1255206-67-7 ]
potassium vinyltrifluoroborate [ No CAS ]
[ 1255206-69-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In ethanol; at 140℃; for 0.333333h;Microwave irradiation;	5-Bromo-4-memyl-2-benzofuran-l(3H)-one (598 mgs 4.47 mmol), potassium vinyl trifluoroborate (507 mgs 2.23 mmmol), PdCl2(dppf)-CEta2Cl2Adduct (182 mg, 0.223 rammol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mJL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 0C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 12Og Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4- methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDCl3): delta ppm 7.76 ( d, J = 8Hz, IH), 7.03(dd, J= 11, 17 Hz5 IH), 5.84 (d, J= 17 Hz5 IH)5 5.55 (d, J- 11 Hz, IH), 5.29 (s5 2H)5 2.34 (s, 3H). LC-MS: M+l= 175; tR = 2.42 min
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation;	5-Bromo-4-methyl-2-benzofuran-l(3H)-one (600 mg, 4.5 mmol), potassium vinyl tnfluoroborate (510 mg, 2.2 mmmol), PdCl2(dppf)-CH2Cl2 Adduct (180 mg, 0.220 mmmol), and TEA (0.62 mL, 4.5 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 minutes. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography (0- 80% ETOAC/Hexane solvent system) to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDC13): delta ppm 7.76 (d, J= 8Hz, 1H), 7.03(dd, 7= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). LC-MS: [M+l] = 175.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	5-Bromo-4-methyl-2-benzofuran-l(3H)-one (600 mg, 4.5 mmol), potassium vinyl trifluoroborate (510 mg, 2.2 mmmol), PdCl2(dppf)-CH2Cl2 Adduct (180 mg, 0.220 mmmol), and TEA (0.62 mL, 4.5 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, and then heated to 140 C for 20 minutes. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, and dried and evaporated to dryness. The crude product was purified by MPLC chromatography (0- 80% ETOAC Hexane solvent system) to yield 5-ethenyl-4-memyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDC13): delta ppm 7.76 (d, J= 8Hz, 1H)5 7,03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 1 1 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). LC-MS: [M+l] = 175.

	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	Step C: 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one: 5-Bromo-4-methyl-2-benzofuran-l(3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2C12 Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% EtOAC/Hexane solvent system to yield the title product. LC-MS: M+l= 175 at 2.42 retention time.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	Step C: 5-ethenyl-4-methyl-2-benzofuran-U3H -one: 5-Bromo-4-methyl-2-benzofuran-l(3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2C12 Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% EtOAC/Hexane solvent system to yield the title product. LC-MS: M+l= 175 at 2.42 retention time.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Inert atmosphere; Sealed tube; Microwave irradiation;	5-Bromo-4-methyl-2-benzofuran- 1 (3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2C12 Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. LC-MS: M+l= 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation;	Step A: 5-Ethenyl-4-methyl-2-benzofuran-l(3H)-one 5- Bromo-4-methyl-2-benzofuran-l(3H)-one (600 mg, 4.5 mmol), potassium vinyl trifluoroborate (510 mg, 2.2 mmmol), PdCl2(dppf)-CH2Cl2 Adduct (180 mg, 0.220 mmmol), and TEA (0.62 mL, 4.5 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography (0-80% ETOAC/Hexane solvent system) to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDC13): delta ppm 7.76 (d, J= 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). LC-MS: [M+l] = 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube; Inert atmosphere; Microwave irradiation;	5-Bromo-4-methyl-2-benzofuran- 1 (3H)-one [INTERMEDIATE 1 ] (600 mg, 4.5 mmol), potassium vinyl trifluoroborate (510 mg, 2.2 mmmol), PdCl2(dppf)-CH2Cl2 Adduct (180 mg, 0.220 mmmol), and TEA (0.62 mL, 4.5 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 minutes. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography (0-80% ETOAC/Hexane solvent system) to yield 5-ethenyl-4-methyl-2- benzofuran- 1 (3H)-one. -NMR (500 MHz, CDC13): delta ppm 7.76 (d, J= 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, = 17 Hz, 1H), 5.55 (d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). LC-MS: [M+l] = 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	Step A: 5-ethenyl-4-methyl-2-benzofuran-1 (3H)-one; 5-Bromo-4-methyl-2-benzofuran-1 (3H)one(598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCb(dppf)-CH2CbAdduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mLethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethylacetate, washed with brine twice, dried and evaporated to dryness. The crude product waspurified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-1(3H)-one. LC-MS: M+1= 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	5-Bromo-4-methyl-2-benzofuran- 1 (3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2Cl2Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDC13): delta ppm 7.76 ( d, J = 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-MS: M+l= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation;	5 -Bromo-4-methyl-2-benzofuran- 1 (3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2Cl2Adduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% EtOAc/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDCI3): delta ppm 7.76 ( d, J = 8Hz, 1H), 7.03(dd, J= 1 1 , 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 1 1 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-MS: M+l= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	5-Bromo-4-methyl-2-benzofuran-l(3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2C12 Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. -NMR (500 MHz, CDCI3): delta ppm 7.76 ( d, J = 8Hz, 1H), 7.03(dd, J= 1 1, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 1 1 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). LC-MS: M+l= 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	Step A: 5-ethenvl-4-methyl-2-benzofuran- 1 (3Th-one: 5-Bromo-4-methyl-2-benzofuran- 1(311)-one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdC12(dppf)-CH2C12 Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mLethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for20 mm. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethylacetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-i(3H)-one. LC-MS: M+1= 175
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	5-Bromo-4-methyl-2-benzofuran- 1 (3H)- one (598 mg, 4.47 mmol), potassium yinyl trifluoroborate (507 mg, 2.23 mmmol), Pdcl2(dppf)- cH2cl2Adduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 methanol in a 20 m microwaye tube. The tube was sealed and degassed, then heated to 140 c for20 min. Analysis by Lc-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and eyaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% EtOAc/Hexane solyent system to yield 5-ethenyl-4-methyl-2-benzofuran-1(3H)-one. 1H-NMR (500 MHz,cDcl3): ppm 7.76 (d, J = 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55(d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); Lc-MS: M+1= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	Step A: S -ethenyl-4-methyl-2-benzofuran- 1(311)-one: S -Bromo-4-methyl-2-benzofuran- 1(311)-one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdC12(dppf)-CH2Cl2Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 mm. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g RediSep column and 0-80% EtOAC/Hexanesolvent system to yield 5-ethenyl-4-methyl-2-benzofuran-1(3H)-one. ?H-NMR (500 MHz, CDC13): oe ppm 7.76 (d, J = 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-MS: M+1= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	S-Bromo-4-methyl-2-benzofuran-i(311)-one (598 mg, 4.47 mmol), potassium vinyltrifluoroborate (507 mg, 2.23 mmmol), PdC12(dppf)-CH2C12 adduct (182 mg, 0.223 mmmol),and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 mm. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4- methyl-2-benzofuran-1(3H)-one. lH-NMR (500 MHz, CDC13): oe ppm 7.76 (d, J = 8Hz, 1H),7.03(dd, J 11, 17Hz, 1H), 5.84 (d, J 17Hz, 1H), 5.55 (d, J 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s,3H); LC-MS: M+1= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	5-Bromo-4-methyl-2-benzofuran-l(3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2Cl2Adduct (182 mg, 0.223 mmmol) and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140C for 20 min. Analysis by LC-LC/MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. ^-NMR (500 MHz, CDCI3): delta ppm 7.76 ( d, J = 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-LC/MS: M+l= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube; Inert atmosphere;	5 -Bromo-4-methyl-2-benzofuran- 1 (311)-one (598 mg, 4.47 mmol), potassium vinyltrifluoroborate (507 mg, 2.23 mmol), PdC12(dppf)-CH2Cl2Adduct (182 mg, 0.223 mmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 mm. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120gRedi-sep column and 0-80% ETOAC/Hexane solvent system to yield the title compound. MS [M+H] = 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube; Inert atmosphere;	5-Bromo-4-methyl-2-benzofuran-1(3H)-one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmol), PdC12(dppf)-CH2Cl2Adduct (182 mg, 0.223 mmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tubewas sealed and degassed, then heated to 140 C for 20 mm. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield the title compound. MS [M+H]= 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube; Microwave irradiation; Inert atmosphere;	Step A: 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one: 5-Bromo-4-methyl-2-benzofuran- 1 (3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2C12 adduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% EtOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2- benzofuran- 1 (3H)-one .
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Sealed tube;	Step A: 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one: 5-Bromo-4-methyl-2-benzofuran-l(3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdC dppf)- CH2C12 adduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% EtOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2- benzofuran- 1 (3H)-one.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	5-Bromo-4-methyl-2-benzofuran-1 (3H) -one (598 mg, 4.47 mmol) (INTERMEDIATE 1) , potassium vinyl trifluoroborate (507 mg, 2.23 mmmol) , PdCl2 (dppf) -CH2Cl2 adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120gcolumn and 0-80 EtOAc/hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-1 (3H) -one. 1H NMR (500 MHz, CDCl3) : delta ppm 7.76 (d, J 8Hz, 1H) , 7.03 (dd, J 11, 17 Hz, 1H) , 5.84 (d, J 17 Hz, 1H) , 5.55 (d, J 11 Hz, 1H) , 5.29 (s, 2H) , 2.34 (s, 3H) LC-MS: M+1 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube; Microwave irradiation;	5-Bromo-4-methyl-2-benzofuran- 1 (3H)- one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)- CH2Cl2Adduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDCI3): delta ppm 7.76 ( d, J = 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-MS: M+l= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;	<strong>[1255206-67-7]5-bromo-4-methyl-2-benzofuran-1(3H)-one</strong> (598 mg, 4.47mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCl2(dppf)-CH2Cl2 Adduct (182 mg, 0.223 mmmol),and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealedand degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixturewas diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product waspurified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system toyield 5-ethenyl-4-methyl-2-benzofuran-1(3H)-one. LC-MS: M+1= 175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	Step A: 5 -ethenyl-4-methyl-2-benzofuran- 1 (311)-one: 5 -Bromo-4-methyl-2-benzofuran- 1(31])-one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdC12(dppf)-CH2Cl2Adduct (182 mg, 0.223 mmmol) , and TEA (0.622 mL, 4.47 mmol) were added to 10 mLethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140C for20 mm. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-1(31])-one. ?H-NMR (500 MHz,CDC13): oe ppm 7.76 (d, J = 8Hz, 1H), 7.03(dd, J= 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55(d, J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-MS: M+1= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	5-Bromo-4-methyl-2-benzofuran- 1 (3H)-one [INTERMEDIATE 11(600 mg, 4.5 mmol), potassium vinyl trifluoroborate (510 mg, 2.2 mmol), PdC12(dppf)-CH2C12 Adduct (180 mg, 0.220 mmol), and TEA (0.62 mE, 4.5 mmol) were added to 10 mE ethanol in a 20 mE microwave tube. The tube was sealed and degassed, then heated to 140 C. for 20 minutes. Analysis by EC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPEC chromatography (0-80% ETOAC/Hexane solvent system) to yield 5-ethenyl-4- methyl-2-benzothran-1 (3H)-one.?H-NMR (500 MHz, CDC13): oe ppm 7.76 (d, J=8 Hz, 1H),7.03 (dd, J=11, 17 Hz, 1H), 5.84 (d, J=17 Hz, 1H), 5.55 (d,J=11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). EC-MS: [M+1]=175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Microwave irradiation; Inert atmosphere;	5-Bromo-4-methyl-2-benzofuran- 1 (3H) one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmmol), PdCi2(dppf)- CH2Cl2Adduct (182 mg, 0.223 mmmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120g RediSep column and 0-80% EtOAc/hexane solvent system to yield 5-ethenyl-4-methyl-2-benzofuran-l(3H)-one. 1H-NMR (500 MHz, CDCls): delta ppm 7.76 ( d, J = 8Hz, 1H), 7.03(dd, J= 1 1 , 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d, J= 1 1 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H); LC-MS: M+l= 175;
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	5-Bromo-4-methyl-2-benzofuran-1(3H)-one (598 mg, 4.47 mmol), potassium vinyl trifluoroborate (507 mg, 2.23 mmol), PdCl2(dppf)-CH2Cl2Adduct (182 mg, 0.223 mmol), and TEA (0.622 mL, 4.47 mmol) were added to 10 mL ethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C. for 20 min. Analysis by LC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried and evaporated to dryness. The crude product was purified by MPLC chromatography using a 120 g Redi-sep column and 0-80% ETOAC/Hexane solvent system to yield the title compound. MS [M+H]+=175.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 140℃; for 0.333333h;Sealed tube;	[0237] 5-Bromo-4-methyl-2-benzofuran-1(3H)-one (600 mg, 4.5 mmol), potassium vinyl trifluoroborate (510 mg, 2.2mmmol), PdCl2(dppf)-CH2Cl2 Adduct (180 mg, 0.220 mmmol), and TEA (0.62 mL, 4.5 mmol) were added to 10 mLethanol in a 20 mL microwave tube. The tube was sealed and degassed, then heated to 140 C for 20 min. Analysis byLC-MS showed product peak. The reaction mixture was diluted with ethyl acetate, washed with brine twice, dried andevaporated to dryness. The crude product was purified by MPLC chromatography (0-80% ETOAC/Hexane solventsystem) to yield 5-ethenyl-4-methyl-2-benzofuran-1(3H)-one.1H-NMR (500 MHz, CDCl3): delta ppm 7.76 (d, J = 8Hz, 1H), 7.03(dd, J = 11, 17 Hz, 1H), 5.84 (d, J= 17 Hz, 1H), 5.55 (d,J= 11 Hz, 1H), 5.29 (s, 2H), 2.34 (s, 3H). LC-MS: [M+1] = 175.

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[16]Patent: WO2015/17305,2015,A1 .Location in patent: Page/Page column 40; 41
[17]Patent: WO2015/65866,2015,A1 .Location in patent: Page/Page column 27; 28
[18]Patent: WO2015/95097,2015,A2 .Location in patent: Page/Page column 28-29
[19]Patent: WO2015/103756,2015,A1 .Location in patent: Page/Page column 45
[20]Patent: WO2015/105736,2015,A1 .Location in patent: Page/Page column 47
[21]Patent: WO2015/96035,2015,A1 .Location in patent: Page/Page column 41
[22]Patent: WO2015/100147,2015,A1 .Location in patent: Page/Page column 41-42
[23]Patent: WO2016/65582,2016,A1 .Location in patent: Page/Page column 32
[24]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 697 - 701
[25]Patent: WO2016/122994,2016,A1 .Location in patent: Page/Page column 34
[26]Patent: EP2744499,2016,B1 .Location in patent: Paragraph 0080
[27]Patent: WO2016/127358,2016,A1 .Location in patent: Page/Page column 30
[28]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5695 - 5702
[29]Patent: US9493474,2016,B2 .Location in patent: Page/Page column 21
[30]Patent: WO2016/60941,2016,A1 .Location in patent: Page/Page column 32; 33
[31]Patent: US2017/37037,2017,A1 .Location in patent: Paragraph 0183
[32]Patent: EP2755656,2016,B1 .Location in patent: Paragraph 0237

4
[ 1255206-67-7 ]
[ 1255206-68-8 ]

Reference： [1]Patent: WO2013/66714,2013,A1
[2]Patent: WO2013/62900,2013,A1
[3]Patent: WO2013/90271,2013,A1
[4]Patent: WO2013/66718,2013,A2
[5]Patent: WO2013/28474,2013,A1
[6]Patent: WO2014/15495,2014,A1
[7]Patent: WO2014/18764,2014,A1
[8]Patent: WO2014/85210,2014,A1
[9]Patent: WO2013/62892,2013,A1
[10]Patent: WO2015/17305,2015,A1
[11]Patent: WO2015/65866,2015,A1
[12]Patent: WO2015/95097,2015,A2
[13]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 747 - 752
[14]Patent: WO2015/103756,2015,A1
[15]Patent: WO2015/105736,2015,A1
[16]Patent: WO2015/100147,2015,A1
[17]Patent: WO2015/96035,2015,A1
[18]Patent: WO2016/65582,2016,A1
[19]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 697 - 701
[20]Patent: WO2016/122994,2016,A1
[21]Patent: EP2744499,2016,B1
[22]Patent: WO2016/127358,2016,A1
[23]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5695 - 5702
[24]Patent: WO2016/60941,2016,A1
[25]Patent: US2017/37037,2017,A1
[26]Patent: EP2755656,2016,B1
[27]Patent: WO2013/39802,2013,A1
[28]Patent: WO2013/66717,2013,A1

5
[ 1255206-67-7 ]
[ 1548296-42-9 ]

Yield	Reaction Conditions	Operation in experiment
	With diisobutylaluminium hydride; In toluene; at -78℃; for 2h;	To a solution of 5-bromo-4- methylisobenzofuran-l(3H)-one (3.45 g, 15.19 mmol) in toluene (100 mL) at -78C was added DIBAL-H (21.27 mL, 21.27 mmol) dropwise. After stirring at -78 C for 2h, the reaction was quenched by methanol at -78C, then warmed to rt , then 20 mL of saturated sodium sulfate was added and the mixture was vigorously stirred at rt for 30 min. Next, the mixture was filtered and washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate, dried over sodium sulfate, then concentrated to give the title compound. LC/MS: (M-17) : 210.92; 212.91.

Reference： [1]Patent: WO2014/18764,2014,A1 .Location in patent: Page/Page column 114

6
[ 1194700-73-6 ]
[ 1255206-67-7 ]

Reference： [1]Patent: WO2014/18764,2014,A1

7
[ 1255206-73-5 ]
[ 1255206-67-7 ]

Reference： [1]Patent: WO2014/18764,2014,A1

8
[ 1548296-37-2 ]
[ 1255206-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In dichloromethane; at 0℃; for 0.5h;	To a solution of 4-methyl-5- (trimethylstannyl)isobenzofuran-l(3H)-one (4.37 g, 14.05 mmol) in DCM (20 mL) was added bromine (0.796 ml, 15.46 mmol) at 0 C. The reaction mixture was stirred at 0 C for 0.5h. Saturated thiosulfate solution was added and the mixture was extracted with methylene chloride (2x100 mL), the combined organic phase was dried over sodium sulfate, concentrated to give 5- bromo-4-methylisobenzofuran-l(3H)-one. LC/MS: (M+l)+:226.89; 228.89.

Reference： [1]Patent: WO2014/18764,2014,A1 .Location in patent: Page/Page column 114

9
[ 1255206-67-7 ]
[ 557-21-1 ]
4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 10h;Inert atmosphere;	To a solution of 5-bromo-4-5 methylisobenzofuran-1(31-I)-one (1.01 g, 4.4mol) in DMF (20 ml) was added Zn(CN)2 (0.52 g,4.4 mol) and Pd(PPh3) 4 (0.5 g, 0.4 mmol) at one portion and the reaction was charged with Arand heated to I 00C for 10 h. The reaction was poured into EtOAc and filtered through akieselguhr pad. The filh·ate was washed with water, brine, dried and concentrated to a brownsolid, which was purified by silica gel column chromatography to give the title compound as al 0 white solid.

Reference： [1]Patent: WO2015/95097,2015,A2 .Location in patent: Page/Page column 55

10
[ 83647-43-2 ]
[ 1255206-67-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of ThalliumTrifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLCshowed no starting material remaining. The solvent was removed under vacuum, and the residuewas pumped under high vacuum for 30 mm to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big productspot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a celite pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford title compound. ?H-NMR (500 MHz, CDC13) oe ppm 7.71 (d, J= 8.0 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).

Reference： [1]Patent: WO2016/127358,2016,A1 .Location in patent: Page/Page column 28; 29

11
[ 236406-39-6 ]
[ 1255206-67-7 ]
tert-butyl 2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 100℃; for 1h;Sealed tube; Inert atmosphere; Microwave irradiation;	A microwave vial containing tert-butyl diazaspiro[4.5]decane-8-carboxylate (100 mg, 0.416 mmol), 5-bromo-4-methylisobenzofuran- l(3H)-one (94 mg, 0.416 mmol), Pd2(dba)3 (19.05 mg, 0.021 mmol), X-Phos (29.8 mg, 0.062 mmol) and potassium phosphate (177 mg, 0.832 mmol) in dioxane (2.080 mL) was sealed and evacuated and purged with nitrogen before heating to 100C for 1 h. The reaction was cooled, diluted with ethyl acetate, filtered and the filtrates concentrated to give crude material which was purified via MPLC (10-75% EtOAc/hexanes) to afford the title compound. LC/MS: [(M+l)]+ = 387.

Reference： [1]Patent: WO2016/60941,2016,A1 .Location in patent: Page/Page column 63; 64

12
[ 236406-39-6 ]
[ 1255206-67-7 ]
C₁₇H₂₂N₂O₂ [ No CAS ]

Reference： [1]Patent: WO2016/60941,2016,A1

13
[ 83647-43-2 ]
thallium(III) trifluoroacetate [ No CAS ]
[ 1255206-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; at 20℃;	To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M TFA solution of Thallium Trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. Analysis by TLC showed no starting material remaining. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 min to ensure complete removal of TFA. To the residue was then added Palladium(II) Chloride (529 mg, 2.98 mmol), Lithium Chloride (2.53 g, 59.7 mmol), Magnesium Oxide (2.41 g, 59.7 mmol), and MeOH (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hr. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a CELITE pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford the title compound. 1H-NMR (500 MHz, CDCl3) delta ppm 7.71 (d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).

Reference： [1]Patent: US2017/37037,2017,A1 .Location in patent: Paragraph 0182

14
[ 869198-95-8 ]
[ 1255206-67-7 ]
tert-butyl 2-((4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 1h;Inert atmosphere; Sealed tube;	To a stirred solution of Intermediate 2 (0.500 g, 1.92 mmol) and5-bromo-4-methylisobenzofuran-1(3H)-one (0.454 g, 1.99 mmol) in dioxane (15 mL) were added K2C03 (0.552 g, 4.00 mmol) and XANTPHOS (0.0580 g, 0.100 mmol). The resulting reaction mixture was degassed with nitrogen for 5 minutes followed by the addition of Pd2(dba)3 (0.183 g, 0.200 mmol). The reaction mixture was degassed withnitrogen for an additional 5 minutes. The reaction mixture was heated 100 C for 1 h by using microwave reactor, cooled and concentrated under reduced pressure. The residue was diluted with EtOAc and filtered through celite. The filtrate was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude solid was purified by CombiFlash (Redisep-24 g, 65 % EtOAc/ n-hexanes), to obtainedIntermediate 5A (0.3 80 g, 48.0 %) as a yellow solid. ?H NMR (400 IVIHz, DMSO-d6) oe ppm 1.40-1.48 (m, 9 H), 2.20 (s, 3 H), 2.74 (t, J= 6.02 Hz, 2 H), 3.64 (t, J= 6.02 Hz, 2H), 4.45 (s, 2 H), 5.38 (s, 2 H), 7.63 (d, J= 8.03 Hz, 1 H), 7.92 (d, J 8.03 Hz, 1 H), 8.32 (s, 1 H), 9.12 (s, 1 H). LCMS (MethodE): retention time 2.42 mi [M+H] 397.2.

Reference： [1]Patent: WO2017/184662,2017,A1 .Location in patent: Page/Page column 69; 70

15
[ 1255206-67-7 ]
[ 74-88-4 ]
5-bromo-3,4-dimethylisobenzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.35 g	With lithium diisopropyl amide; In tetrahydrofuran; at -78 - 20℃; for 16h;	To a stirred solution of <strong>[1255206-67-7]5-bromo-4-methylisobenzofuran-1(3H)-one</strong> (2.0 g, 8.81 mmol) in THF (50 mL) was added LDA (11.01 mL, 22.02 mmol) at -78 oC followed by iodomethane (5.51 mL, 88 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction was poured into ice cold water (40 mL) and extracted with ethyl acetate ( 2 x 25 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by Chiral SFC [Column: Chiralpak ADH (250 x 4.6 mm) 5 micron; 0.2% DEA in MeOH + IPA (1:1), Flow:1.2 mL/min, Temperature: 25 C, UV: 233 nm] to obtain Intermediate 138A-I (0.20 g, 9.46%) as yellow solid, fast eluting (retention time 1.61 min) 1H NMR (400 MHz, CDCl3) delta ppm 1.67 (d, J = 6.36 Hz, 3 H), 2.45 (s, 3 H), 5.60 (q, J = 6.60 Hz, 1 H), 7.60 (d, J = 8.07 Hz, 1 H), 7.76 (d, J = 8.07 Hz, 1 H). LCMS (Method-I): retention time 1.21 min, [M+H] 243.0. and Intermediate 138A-II (0.15 g, 7.09%) as a pale yellow solid, slow eluting (retention time 1.88 min) 1H NMR (400 MHz, DMSO-d6) delta ppm 1.56 (d, J = 6.36 Hz, 3 H), 2.40 (s, 3 H), 5.84 (q, J = 6.60 Hz, 1 H), 7.60 (d, J = 8.07 Hz, 1 H), 7.84 (d, J = 8.07 Hz, 1 H), LCMS (Method-I): retention time 1.21 min, [M+H] 243.0.

Reference： [1]Patent: WO2018/93569,2018,A1 .Location in patent: Page/Page column 221; 222

16
[ 119072-55-8 ]
[ 1255206-67-7 ]
4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38.7%	With triethylsilane; palladium diacetate; potassium carbonate; 1,4-di(diphenylphosphino)-butane; In N,N-dimethyl-formamide; at 65℃; for 8h;Inert atmosphere; Sealed tube;	To a stirred solution of <strong>[1255206-67-7]5-bromo-4-methylisobenzofuran-1(3H)-one</strong> (2.00 g, 8.81 mmol) in DMF (10 mL) was added tert-butyl isocyanide (1.10 g, 13.21 mmol), 1,4- bis(diphenylphosphino)butane (0.37 g, 0.88 mmol), triethylsilane (3.07 g, 26.40 mmol) and K2CO3 (3.04 g, 22.02 mmol) at ambient temperature. The resulting reaction mixture was purged with argon gas for 10 minutes and palladium(II) acetate (0.39 g, 1.76 mmol) was added. The reaction mixture was heated at 65 C in a sealed tube for 8 h and then was cooled to ambient temperature, diluted with water (20 mL), filtered through Celite, and washed with ethyl acetate (2 x 50 mL). The filtrate was washed further with water (30 mL), brine solution (20 mL) and dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified by column chromatography (Redisep-40 g, 0-35% EtOAc/n-Hexane) to obtain Intermediate 87A (0.60 g, 38.70%) as an off-white solid.1H NMR (400 MHz, CDCl3) ppm 2.65 (s, 3 H), 5.35 (s, 2 H), 7.91 - 7.93 (d, J = 8 Hz, 1 H), 7.98 - 8.00 (d, J = 8 Hz, 1 H), 10.4 (s, 1 H). LCMS (Method-D): retention time 1.14 min, [M+H2O] 194.2.

Reference： [1]Patent: WO2018/93569,2018,A1 .Location in patent: Page/Page column 171

17
[ 1255206-67-7 ]
[ 126726-62-3 ]
4-methyl-5-(prop-1-en-2-yl)isobenzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere;	To a stirred solution of <strong>[1255206-67-7]5-bromo-4-methylisobenzofuran-1(3H)-one</strong> (1.00 g, 4.40 mmol) in dioxane (20 mL) and water (4 mL) was added Pd(Ph3P)4 (0.25 g, 0.22 mmol) and sodium carbonate (1.40 g, 13.21 mmol) followed by 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2- dioxaborolane (0.89 g, 5.29 mmol) and the resulting mixture was degassed with nitrogen atmosphere for 10 minutes. The reaction was stirred at 100 oC for 16 h. The reaction mixture was cooled to ambient temperature, concentrated to dryness and the residue was purified by column chromatography (Redisep-24 g, 20-40% EtOAc/n-hexane) to obtain Intermediate 136 (0.80 g, 80 %) as a pale yellow solid.1H NMR (400 MHz, CDCl3) delta ppm 2.08 (s, 3 H), 2.28 (s, 3 H), 4.91 - 4.92 (d, J = 4 Hz, 1 H), 5.24 (s, 2 H), 5.31-5.32 (d, J = 4 Hz, 1 H), 7.30 (d, J = 8.03 Hz, 1 H), 7.72 (s, 1 H), LCMS (Method-I): retention time 1.19 min, [M+H] 189.5.

Reference： [1]Patent: WO2018/93569,2018,A1 .Location in patent: Page/Page column 219

18
[ 1255206-67-7 ]
[ 79099-07-3 ]
tert-butyl 3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-4-oxopiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20.77%	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); caesium carbonate; In toluene; at 110℃; for 12h;Inert atmosphere;	A solution of 5bromo4methylisobenzofuran1(3H)one (1.70 g, 7.53 mmol), tertbutyl 4oxopiperidine1carboxylate (2.50 g, 12.55 mmol) and Cs2CO3 (4.91 g, 15.06 mmol) in toluene (50 mL) was degassed with nitrogen for 20 minutes. PdCl2(dtbpf) (0.81 g, 1.25 mmol) was added and the resulting mixture was degassed again for 10 minutes and then heated at 110 C for 12 h. The reaction mixture was cooled to ambient temperature, filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (Redisep24 g, 60% EtOAc/nhexanes) to obtain Intermediate 4A (0.90 g, 20.77%).1H NMR (400 MHz, DMSOd6) G ppm 1.41 1.47 (m, 9 H), 2.21 (s, 3 H), 2.39 2.48 (m, 1 H), 2.65 2.76 (m, 1 H), 3.47 (br. s., 2 H), 4.04 4.21 (m, 3 H), 5.41 (d, J = 3.01 Hz, 2 H), 7.39 (d, J = 8.03 Hz, 1 H), 7.65 (d, J = 8.03 Hz, 1 H). LCMS (MethodH): retention time 1.92 min, [M+H20] 363.2

Reference： [1]Patent: WO2018/222795,2018,A1 .Location in patent: Page/Page column 61

19
[ 1255206-67-7 ]
[ 73183-34-3 ]
4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.70%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere;	A solution of Intermediate 2A (12.50 g, 55.10 mmol), bispinacolatodiboron (20.97 g, 83.00 mmol) and potassium acetate (16.21 g, 165.00 mmol) in dioxane (200 mL) was degassed with nitrogen for 20 minutes. PdCl2(dppf)2CH2Cl2 (4.50 g, 5.51 mmol) was added and the resulting mixture was degassed again for 10 minutes then was heated at 100 C for 12 h. The reaction was cooled to ambient temperature, filtered through Celite and the filtrate was concentrated under reduced pressure. The resultant residue was washed with nhexane to obtain Intermediate 2B (8.55 g, 56.70%) as a black solid. The compound was taken directly to the subsequent step without further purification.1H NMR (300 MHz, DMSOd6) G ppm 1.28- 1.43 (m, 12 H), 2.46 (s, 3 H), 5.41 (s, 2 H), 7.65 (d, J = 7.9 Hz, 1 H), 7.72- 7.87 (m, 1 H). LCMS (MethodI): retention time 1.43 min, [M+H] 275.1.

Reference： [1]Patent: WO2018/222795,2018,A1 .Location in patent: Page/Page column 57; 58

20
[ 1255206-67-7 ]
[ 1692-25-7 ]
4-methyl-5-(pyridin-3-yl)isobenzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 12h;Inert atmosphere;	General procedure: A solution of 2chloropyrazine (7.94 g, 69.30 mmol), Intermediate 2B (19.00 g, 69.30 mmol), and potassium phosphate tribasic (36.80 g, 173.00 mmol) in a mixture of 1,4dioxane (100 mL) and H2O (20 mL) was degassed with nitrogen for 10 minutes. PdCl2(dppf)2CH2Cl2 (2.83 g, 3.47 mmol) was added and the resulting mixture was degassed again for 10 minutes then was heated at 100 C for 12 h. The reaction mixture was cooled to ambient temperature, filtered through the Celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Redisep330 g, 40% EtOAc/nhexane) to obtain Intermediate 2C (13.00 g, 83.00%) as an offwhite solid.1H NMR (400MHz, DMSOd6) G ppm 2.32 (s, 3 H) , 5.50 (s, 2 H), 7.72 (d, J = 7.5 Hz, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 8.73 (d, J = 2.5 Hz, 1 H), 8.77- 8.87 (m, 1 H), 8.91 (d, J = 2.0 Hz, 1 H). LCMS (MethodH): retention time 1.06 min, [M+H] 227.0.

Reference： [1]Patent: WO2018/222795,2018,A1 .Location in patent: Page/Page column 58; 244

21
[ 5613-26-3 ]
[ 1255206-67-7 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 3960 - 3963

CAS No. :	1255206-67-7	MDL No. :	MFCD26401765
Formula :	C₉H₇BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IRAKZLQFUGTIGE-UHFFFAOYSA-N
M.W :	227.06	Pubchem ID :	59568711
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
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P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
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P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
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P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
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P312	Call a POISON CENTER or doctor/physician if you feel unwell.
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P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
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P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1255206-67-7 ] {[proInfo.proName]}

Quality Control of [ 1255206-67-7 ]

Related Doc. of [ 1255206-67-7 ]

Product Details of [ 1255206-67-7 ]

Safety of [ 1255206-67-7 ]

Application In Synthesis of [ 1255206-67-7 ]

[ 1255206-67-7 ] Synthesis Path-Downstream 1~21

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry