Name: 862081-37-6|5-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2-benzofuran-1-one|98%
Brand: Ambeed
SKU: A349597
Price: 22.0 USD
Availability: InStock
Rating: 97 (27 reviews)

1
[ 64169-34-2 ]
[ 73183-34-3 ]
[ 862081-37-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere; Large scale;	Preparation of 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3H-isobenzofuran-l-one (the compound of formula (IX))Dimethylformamide (1.5L) was sparged with nitrogen for half an hour. Then 5-bromo- 3H-isobenzofuran-l-one (150g, 704mmol), bis(pinacolato)diboron (215g, 847mmol), potassium carbonate (207g, 2.12mol), and Pd(II) acetate (7.9g, 35mmol) were added, and the mixture was heated to 80-105C for 20 hours. The mixture was cooled to 40C and poured into water (4.5L). A solid was isolated by filtration and dried in an oven at elevated temperature under vacuum. The solid was stirred with ethyl acetate (3L) for 2.5 hours, and undissolved material was removed by filtration though a plug of celite. The filtrate was concentrated using a rotary evaporator under vacuum using a water bath for heating, final volume approximately 400mL. The mixture was heated to reflux, allowed to cool to ambient temperature, and cooled with an ice-water bath for approximately half an hour. The title compound was isolated by filtration, washed with ice cold ethyl acetate (two portions of 50ml_ each), and dried in an oven at 40C using vacuum. Yield 76g (41%). HH-NMR (300 MHz, DMSO-d6) delta (ppm) 7.99-7.95 (m, 1H), 7.87-7.83 (m, 2H), 5.43 (s, 2H), 1.34 (s, 12H). A second crop was obtained from the mother liquor and washings; yield 5.6g (3%). NMR as for the first crop
65.7%	With potassium acetate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; at 50 - 80℃; for 16h;Inert atmosphere;	To a stirring solution of 5-bromoisobenzofuran-l(3H)-one (500 mg, 2.34 mmol) in dioxane (30 mL) purged with argon was addedbis(triphenylphosphine)palladium(II)chloride (50 mg, 0.070 mmol) and heated to 50 C. To this was added bis(pinacolato)diboron (1.2 g, 4.6 mmol) and potassium acetate (460 mg, 4.69 mmol) and the resultant reaction mixture was stirred at 80 C for 16 h. The reaction mixture was cooled to RT, filtered through celite bed and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (silica gel, 0-15% ethyl acetate in pet ether) to afford 5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)isobenzofuran-l(3H)-one (Compound-B) as a solid (400 mg, 65.7%)
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 16h;Inert atmosphere;	Step 1: 5-(Tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 ,3-dihydro-2-benzofuran- 1-oneIn a 100 mL round-bottomed flask was added <strong>[64169-34-2]5-bromoisobenzofuran-1(3H)-one</strong> (1.00 g, 4.69 mmol), bis(pinacolato)diboron (1.31 g, 5.16 mmol), PdC12(dppf)-CH2C12 adduct(0.383 g, 0.469 mmol), and potassium acetate (1.15 g, 11.7 mmol) in dioxane (20 mL) to give a suspension. The flask was equipped with a reflux condenser and heated to 80 C with stirring under nitrogen for 16 h. The reaction was partitioned between ethyl acetate (100 mL) and water (50 mL), and the organic layer was dried with Na2SO4, filtered, and concentrated. The reaction mixture was purified using ISCO silica gel chromatography (40 g column, gradient from 0% to 100% EtOAc/hexanes) to give thetitle compound (0.695 g, 57%). ?H NMR (400MHz, DMSO-d6) oe 7.97 (s, 1H), 7.85 (s,2H), 5.43 (s, 2H), 1.33 (s, 12H) HPLC RT = 0.76 mm (Column: Waters Acquity BEHC182.0 x 50 mm; Mobile Phase A: 10:90 ACN:water with 0.1% TFA; Mobile Phase B:90:10 ACN:water with 0.1% TFA; Temperature: 40C; Gradient: 0-100% B over 1.5mm; Flow: 1 mL/min).

57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 16h;Inert atmosphere;	In a 100 ml, round-bottomed flask was added <strong>[64169-34-2]5-bromoisobenzofuran-1(3H)-one</strong> (1.00 g, 4.69 mmol), bis(pinacolato)diboron (1.31 g, 5.16 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.383 g, 0.469 mmol), and potassium acetate (1.15 g, 11.7 mmol) in dioxane (20 mL) to give a suspension. The flask was equipped with a reflux condenser and heated to 80 C. with stirring under nitrogen for 16 h. The reaction was partitioned between ethyl acetate (100 mL) and water (50 mL), and the organic layer was dried with Na2SO4, filtered, and concentrated. The reaction mixture was purified using ISCO silica gel chromatography (40 g column, gradient from 0% to 100% EtOAc/hexanes) to give the title compound (0.695 g, 57%). 1H NMR (400 MHz, DMSO-d6) delta 7.97 (s, 1H), 7.85 (s, 2H), 5.43 (s, 2H), 1.33 (s, 12H) HPLC RT=0.76 min (Column: Waters Acquity BEH C182.0×50 mm; Mobile Phase A: 10:90 ACN:water with 0.1% TFA; Mobile Phase B: 90:10 ACN:water with 0.1% TFA; Temperature: 40 C.; Gradient: 0-100% B over 1.5 min; Flow: 1 mL/min).
	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dichloromethane; dimethyl sulfoxide; at 90℃; for 4h;	Combine 5-bromo-3H-isobenzofuran-l-one (1.0 g, 4.7 mmol), bis- pinocalatodiboron (1.8 g, 7.0 mmol), [1, 1'-bis (diphenylphosphino) - ferocene] dichloropaladium (II) complex with dichloromethane (188 mg, 0.2 mmol) and potassium acetate (1.4 g, 14.0 mmol) in a 100 mL flask with a septum. Add dimethyl sulfoxide (25 mL) and heat in a 90C oil bath for 4 hours. Cool the resulting slurry to room temperature and dilute with water (100 mL). Extract the resulting slurry with dichloromethane (6 x 50 mL). Wash the combined organic layers with brine (40 mL), dry (Na2S04), filter and concentrate in vacuo to obtain 1.3 g of a mixture of the title product and bis-pinocalatodiboron (1 : 0.06), which is used without further purification.
	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃;Inert atmosphere;	Example 35: Synthesis of 5-(5-Fluoro-4-hydroxymethyl-pyridin-3-yl)-3H-isobenzofuran- 1 -one Step 1 : 5-(4,4,5,5-Tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-3H-isobenzofuran-1-one (35a) A 100 round bottom flask was charged with <strong>[64169-34-2]5-bromo-3H-isobenzofuran-1-one</strong> (750 mg, 3.52 mmol), bis(pinacolato)diboron (894 mg, 3.52 mmol), potassium acetate (691 mg, 7.04 mmol) and 1,4-dioxane (25 mL). The reaction mixture was evacuated and flushed with N2 twice followed by addition of PdClz(dppf).CH2CI2 adduct (144 mg, 0.176 mmol). The reaction was stirred under N2 at 100 "C overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with water twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was purified using silica gel flash chromatography employing heptane-ethyl acetate(7:3) to afford 5-(4,4,5,5-tetramethyl- [1 ,3,2]dioxaborolan-2-yl)-3H-isobenzofuran-1-one.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; water; at 80℃; for 48h;Inert atmosphere;	Step 1: Preparation of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-benzofuran-1(3H)-one A mixture of <strong>[64169-34-2]5-bromo-2-benzofuran-1(3H)-one</strong> (500 mg, 2.34 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (653 mg, 2.57 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichlorometahne(1:1) (96 mg, 0.12 mmol), and potassium acetate (689 mg, 7.02 mmol) in dioxane (12 mL) was heated at 80 C. for 48 hours under nitrogen. After cooling to room temperature, water was added and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and filtered through a Celite pad. The filtrate was concentrated and used to the next reaction with no purification. (unstable on silica gel)
	With bis(diphenylphosphino)palladium(II); potassium acetate; In toluene; at 80℃; for 2h;Microwave irradiation;	Step A: 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-benzofuran-l(3H)-one To a microwave tube containing a stir bar was added 5-bromo-2-benzofuran-l (3H)-one (0.10 g, 0.47 mmol), Bis(pinacolato)diboron (0.12 g, 0.47 mmol), bis(diphenylphosphino)palladium(II) (0.010 g, 0.014 mmol), potassium acetate (0.14 g, 1.4 mmol) and anhydrous toluene (10 mL). The resulting mixture was capped and heated at 80 C for 2 h. The reaction mixture was diluted with benzene and washed successively with water and brine. The organic layer was then dried (Na2S04), filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (hexanes/EtOAc = 1/1) to provide 5- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-benzofuran-l(3H)-one. LC/MS: [(M+l)]+ =261.
	With potassium acetate; In toluene; at 80℃; for 2h;	[0200] To a microwave tube containing a stir bar was added 5-bromo-2-benzofuran-1 (3H)-one (0.10 g, 0.47 mmol),Bis(pinacolato)diboron (0.12 g, 0.47 mmol),bis(diphenylphosphino)palladium(II) (0.010 g, 0.014 mmol), potassium acetate (0.14 g, 1.4 mmol) and anhydrous toluene(10 mL). The resulting mixture was capped and heated at 80 C for 2 h. The reaction mixture was diluted with benzeneand washed successively with water and brine. The organic layer was then dried (Na2SO4) filtered, and concentrated.The resulting residue was purified by silica gel column chromatography (hexanes/EtOAc = 1/1) to provide 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-benzofuran-1(3H)-one. LC/MS: [(M+1)]+ =261.

Reference： [1]Patent: WO2014/206903,2014,A1 .Location in patent: Page/Page column 22; 23
[2]Patent: WO2011/134468,2011,A1 .Location in patent: Page/Page column 184
[3]Patent: WO2015/100282,2015,A1 .Location in patent: Page/Page column 352; 353
[4]Patent: US2016/176864,2016,A1 .Location in patent: Paragraph 0929; 0930
[5]Patent: WO2005/73205,2005,A1 .Location in patent: Page/Page column 30-31
[6]Patent: WO2011/61168,2011,A1 .Location in patent: Page/Page column 78
[7]Patent: US2012/108574,2012,A1 .Location in patent: Page/Page column 124
[8]Patent: WO2013/39802,2013,A1 .Location in patent: Page/Page column 53
[9]Patent: EP2755656,2016,B1 .Location in patent: Paragraph 0200

2
[ 64169-34-2 ]
[ 19477-73-7 ]
[ 73183-34-3 ]
[ 862081-37-6 ]
[ 862081-38-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a stirring room temperature solution of 4-bromophthalic anhydride (3.00 g, 13.22 mmol) in ethanol (10 mL) and tetrahydrofuran (50 mL), under a blanket of nitrogen, add sodium borohydride (1.96 g, 52.86 mmol), in portions. Stir this mixture at ambient temperature for 8 hours and then quench with 2N HC1 (12 mL) and then excess water. Extract the resulting aqueous mixture with diethyl ether then ethyl acetate. Wash the combined extracts with water and brine; dry (sodium sulfate) and concentrate them in vacuo to give a mixture of 5-bromo-3H-isobenzofuran-l-one and 6-bromo-3H- isobenzofuran-1-one, 2.78 g (98%). Use as is without purification. Place the mixture of 5-bromo-3H-isobenzofuran-l-one and 6-bromo-3H- isobenzofuran-1-one (1.50 g, 7.04 mmol), bis (pinacolato) diboron (2.06 g, 8.10 mmol), PdCl2 (dppf) 2'CH2Cl2 (180 mg, 0.246 mmol), potassium acetate (2.07 g, 21.13 mmol) and anhydrous dimethyl sulfoxide (22 mL) in a round bottom flask. Put the reaction in an oil bath and stir it at 85C for 8 hours. Cool the dark brown colored reaction to ambient temperature, quench with ample water and extract the resulting aqueous mixture with dichloromethane. Wash the combined extracts with water and brine; then dry (sodium sulfate) and evaporate them in vacuo. Purify the resulting dark solid on a flash column (silica gel; 0%-20% gradient of THF in CH2C12 then 5% MeOH/20% THF/CH2C12) to provide the product as a mixture of the two title components, 785 mg (43%).

Reference： [1]Patent: WO2005/73205,2005,A1 .Location in patent: Page/Page column 29-30

3
[ 648904-51-2 ]
[ 862081-37-6 ]
[ 862081-38-7 ]
[ 862081-39-8 ]
[ 862081-40-1 ]

Yield	Reaction Conditions	Operation in experiment
	With cesium fluoride; tricyclohexylphosphine In acetonitrile at 90℃; for 0.416667h;	15 In a round bottom flask add trifluoromethanesulfonic acid 6-benzyloxy-1- [4- (2- piperidin-l-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester) (592 mg, 0.984 mmol), the mixture of 5- (4, 4,5, 5-tetramethyl- [1, 3,2] dioxaborolan-2-yl)-3H-isobenzofuran-1-one and 6- (4, 4,5, 5-tetramethyl- [1, 3,2] dioxaborolan-2-yl)-3H-isobenzofuran-l-one (0.640 g, 2. 46 mmol), a sonicated suspension of Palladium (II) Acetate (0.049 g, 0.220 mmol) and Tricyclohexylphosphine (0.091 g, 0.320 mmol) in acetonitrile (4 mL), and cesium fluoride (1.35 g, 8.86 mmol). Add acetonitrile (25 mL) and immediately place the reaction in a preheated oil bath at 90°C, and stir for 25 minutes. Then cool the reaction to ambient temperature and filter it through a pad of Celite (rinse with ample, hot ethyl acetate). Wash the filtrate with 50% aqueous sodium carbonate, saturated aqueous ammonium chloride, water and brine; then dry (sodium sulfate) and evaporate it in vacuo. Purify the resulting brown solid foam on a flash column (silica gel; 4%-10% MeOH gradient in CH2C12).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/73205, 2005, A1 Location in patent: Page/Page column 31

4
[ 648904-46-5 ]
[ 862081-37-6 ]
[ 862081-43-4 ]

Yield	Reaction Conditions	Operation in experiment
43%	With cesium fluoride; tricyclohexylphosphine In acetonitrile at 78℃; for 6.5h;	18 Combine trifluoro-methanesulfonic acid 6-methoxy-1- [4-(2-piperidin-1-yl- ethoxy) -phenoxy] -naphthalen-2-yl ester (1.2 mg, 2.4 mmol), 5- (4, 4,5, 5-Tetramethyl- [1, 3,2] dioxaborolan-2-yl)-3H-isobenzofuran-l-one (1.2 g, 4.7 mmol) and acetonitrile (20 mL) in a 100 mL flask with septum. In a separate flask combine palladium (II) acetate (106 mg, 0.5 mmol) and tricyclohexylphisphine (199 mg, 0.7 mmol). Add acetonitrile (5mL) and sonicate for 10 minutes under nitrogen. Add the catalyst slurry and cesium fluoride (3.2 g, 21.2 mmol) to mixture of substances and heat in a 78°C oil bath for 6.5 hours. Cool the resulting suspension to room temperature and filter through packed celite. Rinse the celite with ethyl acetate. Concentrate the filtrate and pre-adsorb the crude product onto silica gel. Chromatograph the residue on a Si02 column eluting the material with methanol in dichloromethane (0 to 25%) to give 514 mg of 5-{6-methoxy- l- [4- (2-piperidin-l-yl-ethoxy)-phenoxy]-naphthalen-2-yl}-3H-isobenzofuran-l-one (43 %). Dissolve 5- {6-methoxy-1- [4- (2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2- yl}-3H-isobenzofuran-l-one (514 mg, 1.0 mmol) in dichloromethane (5 mL), treat the resulting solution with 1M HC1 in diethyl ether (20 mL, 20 mmol) and concentrate the resulting suspension in vacuo to obtain 551 mg of 5- {6-methoxy-1- [4- (2-piperidin-1-yl- ethoxy)-phenoxy]-naphthalen-2-yl}-3H-isobenzofuran-1-one hydrochloride (>99%). Dissolve 5- {6-methoxy-1- [4- (2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2- yl}-3H-isobenzofuran-l-one hydrochloride (551 mg, 1.0 mmol) in dichloromethane (15 mL) and cool to 0°C in an ice-bath. Treat solution with 1M boron tribromide in dichloromethane (4.0 mL, 4.0 mmol), drop wise over 5 minutes and stir for 2.5 hours at 0°C. Add saturated aqueous sodium bicarbonate solution (12 mL) at 0°C and warm to room temperature. Separate the resulting layers and extract the aqueous layer with ethyl acetate (5 x 20 mL). Wash the combined organic layers with brine, dry (Na2SO4) and filter. Concentrate the filtrate and pre-adsorb the crude product onto silica gel. Chromatograph the residue on a Si02 column eluting with methanol in dichloromethane (0 to 20%) to give 245 mg of 5- {6-Hydroxy-1- [4- (2-piperidin-1-yl-ethoxy)-phenoxy]- naphthalen-2-yl}-3H-isobenzofuran-l-one. Dissolve the free-base in dichloromethane (10 mL) and treat with 1M HCl in diethyl ether (20 mL, 10 mmol). Concentrate in vacuo to obtain 235 mg of the title compound (44%): mass spectrum (ion spray): m/z = 496. 3 (M+H-HC1).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/73205, 2005, A1 Location in patent: Page/Page column 33-34

5
[ 862081-37-6 ]
[ 1227573-02-5 ]
[ 1308670-19-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 100℃; for 1h;Inert atmosphere;	Step 2: 3-fluoro-5-(1-oxo-1 ,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde (35b) To 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3H-isobenzofuran-1-one (210 mg, 0.809 mmol) in DMF (4 mL) was added <strong>[1227573-02-5]3-bromo-5-fluoro-pyridine-4-carbaldehyde</strong> (150 mg, 0.735 mmol) and 2M aqueous sodium carbonate (0.735 mL, 1.471 mmol). The reaction mixture was flushed and evacuated with N2 twice followed by the addition of PdCI2(dppf).CH2CI2 adduct (30.0 mg, 0.037 mmol). The reaction mixture was stirred at 100 °C for 1 hour. The reaction was cooled to room temperature, diluted with ethyl acetate and washed with water twice. The organic layer was separated, dried over sodium sulfate and concentrated in vacuo to afford 3-fluoro-5-(1 -oxo-1 ,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde, which was taken into the next step without further purification.

Reference： [1]Patent: WO2011/61168,2011,A1 .Location in patent: Page/Page column 78-79

6
[ 862081-37-6 ]
[ 1227573-02-5 ]
[ 1308669-44-4 ]

Reference： [1]Patent: WO2011/61168,2011,A1

7
[ 862081-37-6 ]
[ 697785-99-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / ethanol; toluene / 2 h / Reflux; Inert atmosphere 2: hydrogenchloride; water / acetone / 3 h / 20 °C 3: piperidine / ethanol / 72 h / 20 °C
	Multi-step reaction with 3 steps 1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / ethanol; water; toluene / 2 h / Reflux; Inert atmosphere 2: hydrogenchloride / water; acetone / 3 h / 20 °C 3: piperidine / ethanol / 72 h / 20 °C

Reference： [1]Spicer, Julie A.; Huttunen, Kristiina M.; Miller, Christian K.; Denny, William A.; Ciccone, Annette; Browne, Kylie A.; Trapani, Joseph A. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 3, p. 1319 - 1336]
[2]Current Patent Assignee: THE UNIVERSITY OF AUCKLAND; PETER MACCALLUM CANCER CENTER - WO2011/75784, 2011, A1

8
[ 862081-37-6 ]
[ 392704-83-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / ethanol; toluene / 2 h / Reflux; Inert atmosphere 2: hydrogenchloride; water / acetone / 3 h / 20 °C
	Multi-step reaction with 2 steps 1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / ethanol; water; toluene / 2 h / Reflux; Inert atmosphere 2: hydrogenchloride / water; acetone / 3 h / 20 °C

Reference： [1]Spicer, Julie A.; Huttunen, Kristiina M.; Miller, Christian K.; Denny, William A.; Ciccone, Annette; Browne, Kylie A.; Trapani, Joseph A. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 3, p. 1319 - 1336]
[2]Current Patent Assignee: THE UNIVERSITY OF AUCKLAND; PETER MACCALLUM CANCER CENTER - WO2011/75784, 2011, A1

9
[ 32529-50-3 ]
[ 862081-37-6 ]
[ 1313397-90-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium carbonate In ethanol; water; toluene for 2h; Reflux; Inert atmosphere;	2 This cyclic acetal (666 mg, 3.04 mmol) was dissolved in toluene (27 mL), to which was added a suspension of 5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)isobenzofuran-l (3H)-one (527 mg, 2.03 mmol) in EtOH (10 mL). This boronate ester was prepared in turn from 5-bromoisobenzofuran-l (3H)-one2 according to a literature procedure.3 The entire mixture was heated at reflux under nitrogen for 2 h., then upon cooling, all solvents were removed under reduced pressure and the resulting residue was partitioned between water (50 mL) and CH2C12 (50 mL). Two further CH2C12 (50 mL) extractions were performed, then the combined organic fractions dried (Na2'S04), filtered, and the solvent removed under reduced pressure to afford a residue which was purified by flash column chromatography on silica gel (10% EtOAc/hexanes as eluant). The title compound was isolated as a beige solid (416 mg, 75%). NMR [400 MHz, (CD3)2SO] δ 7.98 (s, 1 H), 7.92 (dd, J= 8.1, 1.2 Hz, 1 H), 7.88 (d, J= 8.1 Hz, 1 H), 7.21 (d, J = 3.5 Hz, 1 H), 6.73 (d, J = 3.4 Hz, 1 H), 5.98 (s, 1 H), 5.44 (s, 2 H), 4.05-4.14 (m, 2 H), 3.94-4.03 - (m, 2 H).
75%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In ethanol; toluene for 2h; Reflux; Inert atmosphere;	4.1.1. General procedure A: 5-(5-(1,3-dioxolan-2-yl)furan-2-yl)isobenzofuran-1(3H)-one (23) 5-Bromo-2-furaldehyde was protected as the cyclic acetal 3 according to a literature procedure.43 The cyclic acetal (666 mg, 3.04 mmol) was dissolved in toluene (27 mL), to which was added a suspension of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one 22 (527 mg, 2.03 mmol) in EtOH (10 mL). This boronate ester was prepared in turn from 5-bromoisobenzofuran-1(3H)-one3362 according to a literature procedure.34 A solution of 2 M Na2CO3 (6.6 mL) and Pd(dppf)Cl2 (90 mg, 0.10 mmol) were added and the entire mixture was heated at reflux under nitrogen for 2 h. Upon cooling, all solvents were removed under reduced pressure and the resulting residue was partitioned between water (50 mL) and CH2Cl2 (50 mL). Two further CH2Cl2 (50 mL) extractions were performed, then the combined organic fractions dried (Na2SO4), filtered, and the solvent removed under reduced pressure to afford a residue which was purified by flash column chromatography on silica gel (10% EtOAc/hexanes as eluant). The title compound 23 was isolated as a beige solid (416 mg, 75%). 1H NMR [(CD3)2SO] δ 7.98 (s, 1H), 7.92 (dd, J = 8.1, 1.2 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.21 (d, J = 3.5 Hz, 1H), 6.73 (d, J = 3.4 Hz, 1H), 5.98 (s, 1H), 5.44 (s, 2H), 4.05-4.14 (m, 2H), 3.94-4.03 (m, 2H).

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF AUCKLAND; PETER MACCALLUM CANCER CENTER - WO2011/75784, 2011, A1 Location in patent: Page/Page column 47-48
[2]Location in patent: experimental part Spicer, Julie A.; Huttunen, Kristiina M.; Miller, Christian K.; Denny, William A.; Ciccone, Annette; Browne, Kylie A.; Trapani, Joseph A. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 3, p. 1319 - 1336]

10
[ 862081-37-6 ]
[ 1345882-01-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: caesium carbonate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 4 h / 90 °C / Inert atmosphere 2: hydrogenchloride; water / methanol / 1 h / 50 °C