[ CAS No. 87199-18-6 ]

Name: 87199-18-6|(3-Hydroxyphenyl)boronic acid|98%
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Quality Control of [ 87199-18-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 87199-18-6 ]

CAS No. :	87199-18-6	MDL No. :	MFCD01074603
Formula :	C₆H₇BO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WFWQWTPAPNEOFE-UHFFFAOYSA-N
M.W :	137.93	Pubchem ID :	2734359
Synonyms :

Calculated chemistry of [ 87199-18-6 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	38.29
TPSA :	60.69 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.47
Log Po/w (WLOGP) :	-0.93
Log Po/w (MLOGP) :	-0.36
Log Po/w (SILICOS-IT) :	-1.2
Consensus Log Po/w :	-0.4

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.37
Solubility :	5.89 mg/ml ; 0.0427 mol/l
Class :	Very soluble
Log S (Ali) :	-1.31
Solubility :	6.7 mg/ml ; 0.0486 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.68
Solubility :	28.6 mg/ml ; 0.207 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.59

Safety of [ 87199-18-6 ]

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:

Application In Synthesis of [ 87199-18-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 87199-18-6 ]
Downstream synthetic route of [ 87199-18-6 ]

[ 87199-18-6 ] Synthesis Path-Upstream 1~9

1
[ 87199-18-6 ]
[ 98-88-4 ]
[ 6949-73-1 ]

Reference： [1] ChemCatChem, 2016, vol. 8, # 20, p. 3207 - 3212

2
[ 121-43-7 ]
[ 591-20-8 ]
[ 87199-18-6 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sec.-butyllithium In tetrahydrofuran	(vi) Preparation of 3-hydroxylphenyl boronic acid 3-Bromophenol (8.65 g, 50 mmol) in dry THF (150 mL) was treated with sodium hydride (60percent, 2.4 g, 60 mmol) at r.t. After 1 h, sec-butyllithium (1.3 M, 50 mL, 65 mmoL) was added dropwise to the reaction solution at -78° C. The reaction mixture was then allowed to stir at the same temperature for 30 min prior to addition of trimethyl borate (15 mL). After warming up to r.t. for 2 hrs, the reaction mixture was quenched with water (50 mL), and extracted with dichloromethane (2*100 mL). The combined organic phases were dried over MgSO₄ and evaporated to give the title compound as a white solid (4.0 g, 58 percent), which was used in the Suzuki coupling reactions without further purification.

Reference： [1] Patent: US2003/187022, 2003, A1,

3
[ 30418-59-8 ]
[ 87199-18-6 ]

Reference： [1] Journal of the American Chemical Society, 1932, vol. 54, p. 4415,4418
[2] Patent: US2007/209123, 2007, A1, . Location in patent: Page/Page column 7

4
[ 108-43-0 ]
[ 87199-18-6 ]

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
[2] Organic Letters, 2012, vol. 14, # 18, p. 4814 - 4817,4

5
[ 13331-27-6 ]
[ 87199-18-6 ]

Reference： [1] Journal of the American Chemical Society, 1932, vol. 54, p. 4415,4418

6
[ 76-09-5 ]
[ 87199-18-6 ]
[ 214360-76-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	at 20℃; for 48 h;	To a 500 mL three-necked flask, 3-hydroxyphenylboronic acid (10.0 g, 72.46 mmol, 1.0 eq) and methylene chloride (300 mL) were added, and pinacol (10.0 g, 84.60 mmol, 1.2 eq) was added under stirring, followed by stirring at room temperature for 48 h. The reaction solution was poured into water (400 mL). The mixed solution was poured into a separatory funnel. The organic phase was separated and the aqueous phase was extracted twice with dichloromethane (400 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The crude product was purified by column chromatography (200-300 mesh silica gel, methylene chloride/methanol mixed solvent at a volume ratio of 100/1 as eluent) to obtain 15.0 g of a white solid with a yield of 94percent and a purity of 97percent.

Reference： [1] Patent: CN107188901, 2017, A, . Location in patent: Paragraph 0035; 0036
[2] Organic Letters, 2010, vol. 12, # 23, p. 5474 - 5477

7
[ 87199-18-6 ]
[ 871231-45-7 ]

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
[2] Organic Letters, 2012, vol. 14, # 18, p. 4814 - 4817,4

8
[ 585-76-2 ]
[ 87199-18-6 ]
[ 171047-01-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate In 1,4-dioxane; water at 95℃; Inert atmosphere	General procedure: The halo aryl (1.0 equiv) was dissolved in a mixture of water:dioxane (1:1). The boronic acid or ester(1.5 equiv) and potassium phosphate (5.0 equiv) were added. The solution was degassed byvacuum/argon cycles (10 times) before addition of PdCl2(PPh3)2 (10 molpercent) and further degassed (5times). The resulting mixture was stirred at 95 °C under argon atmosphere for 16-20 hours. Thereaction mixture was filtered through Celite and diluted with water (approx. 30 mL) before washingwith chloroform (3 x 30 mL). If not stated otherwise, the aqueous phase was concentrated underreduced pressure and applied to a C18 precolumn before purification on a 10g or 60 g C18 column witha gradient of acetonitrile in water (10-100percent) to yield the desired product.

Reference： [1] European Journal of Medicinal Chemistry, 2018, vol. 145, p. 634 - 648

9
[ 87199-18-6 ]
[ 1293915-42-0 ]

Reference： [1] Patent: WO2012/52753, 2012, A1,
[2] Patent: WO2013/136075, 2013, A1,

[ 87199-18-6 ] Synthesis Path-Downstream 1~68

1
[ 87199-18-6 ]
[ 90914-41-3 ]
[ 108-42-9 ]
3-(3-hydroxy-phenyl)-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine [ No CAS ]

Reference： [1]Organic Letters,2003,vol. 5,p. 3587 - 3590

2
[ 591-20-8 ]
[ 87199-18-6 ]
[ 612-76-0 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 4104 - 4118
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 4998 - 5008

3
[ 22726-00-7 ]
[ 87199-18-6 ]
[ 681161-44-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 60℃; for 24h;	Water (10 ml), sodium carbonate (4.76 g) and tetrakistriphenylphosphine palladium (866 mg) were added in that order to a dimethoxyethane (50 ml) solution containing <strong>[22726-00-7]3-bromobenzamide</strong> (3.0 g) and (3-hydroxyphenyl)boronic acid (2.27 g), followed by stirring at 60C for 24 hours. The reaction solution was cooled, diluted with EtOAc, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: EtOAc) to obtain a pale yellow powder (2.74 g). Using the resulting compound and in the same manner as in Reference Example 1, the compound of Reference Example 28 was obtained.

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4998 - 5008
[2]Patent: EP1849773,2007,A1 .Location in patent: Page/Page column 28

4
[ 28229-69-8 ]
[ 87199-18-6 ]
3'-(2-hydoxyethyl)biphenyl-3-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4998 - 5008

5
[ 101066-87-9 ]
[ 87199-18-6 ]
C₁₄H₈F₃NO [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5529 - 5532

6
[ 87199-18-6 ]
[ 209808-18-4 ]
[ 692246-40-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate In ethanol; water; toluene at 90℃; for 5h;	7 INTERMEDIATE 7: tert-butyl 4- [ {4- [ (DIETHYLAMINO) carbonyl] phenyl} (3- hydroxyphenyl) methylene] piperidine-1-carboxylate A solution of INTERMEDIATE 5 (4.08 g, 9.04 mmol), 3-hydroxyphenylboronic acid (1.97 g, 14.3 mmol) and aqueous 2N sodium carbonate (11.3 mL, 22.6 mmol) in a 1: 1 mixture of toluene/ethanol (200 mL) was degassed for 20 minutes. Palladium tetrakistriphenylphosphine (1.05 g, 0.909 mmol) was added and the reaction mixture was purged with nitrogen and heated to 90 °C. After 5 h, the reaction was cooled to room temperature and saturated aqueous ammonium chloride was added. The mixture was extracted with two portions of ethyl acetate and the combined organic extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by flash chromatography eluting with 0% to 100% ethyl acetate in hexanes to yield INTERMEDIATE 7 as a white solid (4.24 g, 100%). 1H NMR (400MHZ, CDC13) 8 1.10 (t, J = 7.42 Hz, 3H), 1.20 (t, J = 7.03 Hz, 3H), 1.42 (s, 9H), 2.25-2. 33 (m, 4H), 3.23-3. 31 (m, 2H), 3.39-3. 46 (m, 4H), 3.46-3. 54 (m, 2H), 6.51 (dd, J = 2.15, 1.56 Hz, 1H), 6.57 (ddd, J = 7.62, 1.56, 0.98 Hz, 1H), 6.62 (ddd, J = 8.20, 2.54, 0.98 Hz, 1H), 7.06-7. 12 (m, 1H), 7.19 (d, J = 8.40 Hz, 2H), 7.29 (d, J = 8.40 Hz, 2H).
100%	With sodium carbonate In ethanol; water; toluene at 90℃; for 5h;	6 INTERMEDIATE 6: TERT-BUTYL 4- [ {4- [ (DIETHYLAMINO) CARBONYL] PHENYL} (3- hydroxyphenyl) methylene] PIPERIDINE-1-CARBOXYLATE To a flask containing INTERMEDIATE 5 (4.08 g, 9.04 mmol) was added toluene (100 ML), ethanol (100 mL), 3-hydroxyphenylboronic acid (1. 97 g, 14.3 MMOL), and aqueous 2N sodium carbonate (11. 3 mL, 22.6 MMOL). The solution was degassed for 20 minutes, then palladium tetrakistriphenylphosphine (1. 05 g, 0.909 mmol) was added. The reaction mixture was purged with nitrogen and heated to 90 °C. After 5 h, the reaction was cooled to rt and saturated aqueous ammonium chloride was added. The mixture was extracted with two portions of ethyl acetate and the combined organic extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by flash chromatography, eluting 0% to 100% ethyl acetate in hexanes, to yield INTERMEDIATE 6 as a colourless solid (4.24 g, 100%).'H NMR (400MHZ, CDCL3) 6 1. 10 (t, J = 7.42 Hz, 3H), 1.20 (t, J = 7.03 Hz, 3H), 1.42 (s, 9H), 2.25-2. 33 (M, 4H), 3.23-3. 31 (M, 2H), 3.39-3. 46 (M, 4H), 3.46-3. 54 (M, 2H), 6.51 (dd, J = 2.15, 1. 56 Hz, 1H), 6.57 (ddd, J = 7.62, 1.56, 0.98 Hz, 1H), 6.62 (ddd, J = 8. 20, 2.54, 0.98 Hz, 1H), 7.06-7. 12 (M, 1H), 7.19 (d, J = 8.40 Hz, 2H), 7.29 (d, J = 8. 40 Hz, 2H).
100%	With sodium carbonate In ethanol; water; toluene at 20 - 90℃; for 5.33333h;	INTERMEDIATE 7: tert-butyl 4-[{4-[(DIETHYLAMINO) CARBONYL] PHENYL} (3- hydroxyphenyl) methylene] piperidine-I-carboxylate To a flask containing INTERMEDIATE 5 (4.08 g, 9.04 mmol) was added toluene (100 mL), ethanol (100 mL), 3-hydroxyphenylboronic acid (1.97 g, 14.3 MMOL), and aqueous 2N sodium carbonate (11. 3 mL, 22.6 MMOL). The solution was degassed for 20 minutes, then palladium tetrakistriphenylphosphine (1. 05 g, 0.909 mmol) was added. The reaction mixture was purged with nitrogen and heated to 90 °C. After 5 h, the reaction was cooled to rt and saturated aqueous ammonium chloride was added. The mixture was extracted with two portions of ethyl acetate and the combined organic extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by flash chromatography, eluting 0% to 100% ethyl acetate in hexanes, to yield INTERMEDIATE 7 as a colourless solid (4.24 g, 100%). 1H NMR (400MHZ, CDCL3) No. 1.10 (t, J = 7.42 Hz, 3H), 1.20 (t, J = 7.03 Hz, 3H), 1.42 (s, 9H), 2.25-2. 33 (m, 4H), 3.23-3. 31 (m, 2H), 3.39-3. 46 (m, 4H), 3.46-3. 54 (m, 2H), 6.51 (dd, J = 2.15, 1.56 Hz, 1H), 6.57 (ddd, J = 7.62, 1.56, 0.98 Hz, 1H), 6.62 (ddd, J = 8. 20, 2.54, 0.98 Hz, 1H), 7.06-7. 12 (m, 1H), 7.19 (d, J = 8.40 Hz, 2H), 7.29 (d, J = 8. 40 Hz, 2H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2004/41784, 2004, A1 Location in patent: Page 65
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2004/101521, 2004, A1 Location in patent: Page 18; 33-34
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2004/100952, 2004, A1 Location in patent: Page 40

7
[ 109-04-6 ]
[ 87199-18-6 ]
[ 98061-22-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With phosphate potassium salt In DMF (N,N-dimethyl-formamide) at 80℃; for 12.25h;	XV. E 3-Pyridin-2-yl-phenol [0284] In a vial, a mixture of potassium phosphate (1.28 g, 6 mmol), 2- bromo-pyridine (0.2 mL, 2 mmol), 3-hydroxy-phenylboronic acid (338 mg, 2.4 mmol) in DMF (4 mL) was purged with argon while stirring for 15 min. After Pd (PPh3) 4 (235 mg, 0.1 mmol) was added and the vial was sealed. The mixture was heated for 12 h at 80 °C and at room temp, the mixture was quenched with water (lmL). The mixture was extracted with dichloromethane once the pH was adjusted to 7-8 with 10 % HC1. The combined organic phase was concentrated. The residue in ethyl acetate (35 mL) was washed with brine (5 x 20 mL) and water (25 mL) then concentrated. Flash column chromatography provided the product (300 mg, 88 %). 1H NMR (acetone-d6). No. : 6.92 (ddd, 1H, J = 8.0, 2.5 & 0.9 Hz), 7.32 (m, 2H), 7.59 (ddd, 1H, J = 7. 8, 2.5 & 1.0 Hz), 7. 67 (dd, 1H, J = 2.3 & 1.9 Hz), 7. 88 (m, 2H), 8.49 (s, 1H, OH), 8.66 (ddd, 1H, J = 4.8, 1.7 &1. 0 Hz).
81%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water; toluene Reflux;
76.1%	With potassium phosphate; palladium diacetate In water; isopropyl alcohol for 6h; Reflux;	1 synthesis of 3-(2-pyridyl)phenol (4-C) synthesis of 3-(2-pyridyl)phenol (4-C) Sequentially 1. 66g (12mmol) 3- hydroxyphenyl boronic acid (4-A), L 58g (lOmmol) 2- bromopyridine (4-B), 5. 33g (25mmol) potassium phosphate, 45mg (0. 2mmol) palladium acetate, 50ml of isopropanol and 50ml of water were added to a 250ml three reaction flask was heated to reflux for 6 hours. Completion of the reaction, after removal of isopropanol by rotary evaporation plus 40ml X 3 and extracted with ethyl acetate, dried over anhydrous magnesium sulfate and filtered two hours, solvent removal, crystallization, and dried to give 1. 32g as a pale yellow solid, i.e. Compound 4 -C, content of 98. 6% (HPLC), yield 76.1%.

76.1%	With potassium phosphate; palladium diacetate In water; isopropyl alcohol at 80℃; for 6h;	1 Synthesis of 3-(2-pyridinyl)phenol (4-C) 3-hydroxyphenylboronic acid (formula 4-A, 20 mmol, 2.77 g), 2-bromopyridine (formula 4-B, 10 mmol, 1.58 g), potassium phosphate (30 mmol, 6.39 g), palladium acetate (0.2 mmol, 45 mg), isopropanol (50 ml) and water (50 ml) were added to a 250 ml, three-necked reaction flask successively, heated to 80° C. to react for 6 hours. When the reaction was finished, isopropanol was removed by rotary evaporation and ethyl acetate (40 ml×3) was added for extraction, then the obtained organic phase was dried, filtered, desolventized, crystallized and dried to obtain 1.32 g of pale yellow solid, i.e. compound 4-C, with the content of 98.6% (HPLC) and the yield of 76.1%.
65%	With 1,1',1'',1'''-benzene-1,2,4,5-tetrayltetrakis(methylene)tetrakis-(piperidin-4-ol); palladium diacetate; potassium carbonate In ethanol; water at 20℃;

Reference： [1]Current Patent Assignee: ENDORECHERCHE, INC. - WO2005/66194, 2005, A1 Location in patent: Page/Page column 165-166
[2]Zhang, Yi; Zhao, Yu; Luo, Yu; Xiao, Liuqing; Huang, Yuxing; Li, Xingrong; Peng, Qitao; Liu, Yizhen; Yang, Bo; Zhu, Caizhen; Zhou, Xuechang; Zhang, Junmin [Organic Letters, 2017, vol. 19, # 24, p. 6470 - 6473]
[3]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN103910670, 2016, B Location in patent: Paragraph 0052; 0054; 0055
[4]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - US2017/1961, 2017, A1 Location in patent: Paragraph 0026; 0027
[5]Nallasivam, Jothi L.; Fernandes, Rodney A. [European Journal of Organic Chemistry, 2015, vol. 2015, # 16, p. 3558 - 3567]

8
[ 87199-18-6 ]
[ 120157-97-3 ]
[ 921625-82-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; tricyclohexylphosphine;palladium diacetate; In 1,4-dioxane; water; at 90℃; for 3h;Micro wave conditions;	A mixture of [2-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (500 mg), 3-hydroxy- benzeneboronic acid (296 mg), sodium carbonate (265 mg), palladium (II) acetate (7 mg) and tricyclohexylphosphine (10 mg) in water (3 ml) and dioxane (12 ml) is kept at 90C under micro wave conditions for 180 min. The mixture is cooled down to rt and is filtered through an EXTUBE extraction column (Varian) with EtOAc ( 200 ml). The filtrate is evaporated and the resulting crude product is purified on silica (15Og) with cyclohexane /EtOAc 5/1 to afford pure [2-(3'-hydroxy-biphenyl-4-yl)-ethyl]-carbamic acid tert-butyl ester.MS (ESI+): 336 [M+Na]; Rf: (EtOAc/hexane = 1/2): 0.28.

Reference： [1]Patent: WO2007/9715,2007,A1 .Location in patent: Page/Page column 34

9
[ 68819-84-1 ]
[ 87199-18-6 ]
[ 880156-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; tricyclohexylphosphine;palladium diacetate; In 1,4-dioxane; water; at 90℃; for 3.83333h;Micro wave conditions;	(3'-Hydroxy-biphenyl-4-ylmethyl)-carbamic acid tert-butyl ester A mixture of (4-bromo-benzyl)-carbamic acid tert-butyl ester (600 mg), 3-hydroxybenzene- boronic acid (373 mg), sodium carbonate (333 mg), palladium (II) acetate (10 mg) and tri- cyclohexylphosphine (13 mg) in water (3.5 ml) and dioxane (14 ml) is kept at 900C under micro wave conditions for 230 min. The mixture is cooled down to rt and is filtered through an EXTUBE extraction column with EtOAc ( 200 ml). The filtrate is evaporated and the resulting crude product is purified on silica (9Og) with cyclohexane /EtOAc 95:5 to 70:30 to afford pure (3'-hydroxy-biphenyl-4-ylmethyl)-carbamic acid tert-butyl ester.MS (ESI+): 322 [M+Na]; Rf: (EtOAc/hexane = 1/2): 0.28.

Reference： [1]Patent: WO2007/9715,2007,A1 .Location in patent: Page/Page column 30

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 150℃; for 3h;Reactivity (does not react);	No evidence of product formation corresponding to xanthene structure.

11
[ 905590-33-2 ]
aqueous potassium carbonate [ No CAS ]
[ 87199-18-6 ]
[ 247940-06-3 ]
4-(3,4-diethoxyphenyl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0);	Example 134 4-(3,4-diethoxyphenyl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide Using N-(4-chloro-6-phenylpyridin-2-yl)-4-(3,4-diethoxyphenyl)-4-oxobutanamide obtained in Example 43-(3) (22.6 mg), tris(dibenzylideneacetone)dipalladium (1.1 mg), biphenyl-2-yl(dicyclohexyl)phosphine (1.8 mg), 1N aqueous potassium carbonate solution (0.1 mL) and (3-hydroxyphenyl)boronic acid (17.2 mg) as starting materials and in the same manner as in Example 119, 4-(3,4-diethoxyphenyl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide (11.0 mg) was obtained. HPLC (220 nm) purity 91% (retention time 1.94 min) MS (ESI+, m/e) 511 (M+H)

Reference： [1]Patent: EP1845081,2007,A1

12
[ 905590-58-1 ]
aqueous potassium carbonate [ No CAS ]
[ 87199-18-6 ]
[ 247940-06-3 ]
4-(2,3-dihydro-1-benzofuran-5-yl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0);	Example 165 4-(2,3-dihydro-1-benzofuran-5-yl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide Using N-(4-chloro-6-phenylpyridin-2-yl)-4-(2,3-dihydro-1-benzofuran-5-yl)-4-oxobutanamide obtained in Example 114-(1) (20.3 mg), tris(dibenzylideneacetone)dipalladium (1.1 mg), biphenyl-2-yl(dicyclohexyl)phosphine (1.8 mg), 1N aqueous potassium carbonate solution (0.1 mL) and (3-hydroxyphenyl)boronic acid (17.2 mg) as starting materials and in the same manner as in Example 119, 4-(2,3-dihydro-1-benzofuran-5-yl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide (11.5 mg) was obtained. HPLC (220 nm) purity 91% (retention time 1.88 min) MS (ESI+, m/e) 465 (M+H)

Reference： [1]Patent: EP1845081,2007,A1

13
[ 4010-81-5 ]
[ 87199-18-6 ]
[ 934545-07-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 180℃; for 1h;	A mixture of <strong>[4010-81-5]4-(2-chloro-9H-purin-6-yl)morpholine</strong> (0.18 g, 0.75 mmol), tetrakis(triphenylphosphine)palladium (30 mg), and 3-hydroxyphenylboronic acid (0.16 g, 1.1 mmol) in 1,2-dimethoxyethane (2.6 mL) and 2 M aqueous sodium carbonate (0.75 mL) was heated in a microwave reactor for one hour at 180 C. After being allowed to cool to room temperature, the mixture was acidified with 5% aqueous potassium hydrogen sulfate solution and then extracted with ethyl acetate. Organics were washed successively with water and saturated aqueous sodium hydrogen carbonate solution, then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford a crude white solid. The crude material was purified by reverse phase HPLC, employing a gradient elution of 85% A solvent (0.1% aqueous trifluoroacetic acid) to 100% B solvent (acetonitrile) to afford 3-(6-morpholino-9H-purin-2-yl)phenol as a white powder (80 mg). MS (ES+): 298.0 (M+H)+

Reference： [1]Patent: US2008/233127,2008,A1 .Location in patent: Page/Page column 37
[2]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 636 - 639
[3]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 653 - 656

14
[ 104-92-7 ]
[ 87199-18-6 ]
[ 33104-27-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With palladium diacetate; potassium carbonate In tetrahydrofuran; water monomer for 5h; Inert atmosphere; Reflux;
78%	With palladium diacetate; potassium carbonate In water monomer; acetone at 20℃; for 0.333333h; Inert atmosphere;	PATHWAY G PATHWAY G Nitrogen was bubbled through a mixture of 1-bromo-4-methoxybenzene (5.0 g, 26.8 mmol), 3-hydroxyphenylboronic acid (6.8 g, 49.6 mmol), aqueous potassium carbonate (2 M, 20 mL, 40 mmol), acetone (170 mL) and H20 (300 mL) for 5 minutes. Pd(OAc)2 (800 mg,3.55 mmol) was added and the mixture was stirred under a nitrogen atmosphere at room temperature for 20 minutes, after which time LC-MS analysis showed the reaction to be complete. The reaction mixture was concentrated under vacuum then diluted with ethyl acetate (200 mL). The resulting suspension was filtered through a pad of celite, and the aqueous phase was then separated and extracted with EtOAc (2 x 100 mL). The combined organics were dried over MgSO4, filtered and concentrated to dryness under vacuum. The crude product was loaded onto a 340 g Biotage silica cartridge and purified by Biotage chromatography (eluting with iso-hexane/EtOAc, gradient 0 to 50 %). The target compound 4’-methoxy-[1,1’-biphenyll-3-ol was isolated as a white solid (5.66 g, 78 % yield).
78%	With palladium diacetate; potassium carbonate In water monomer; acetone at 20℃; for 0.416667h; Inert atmosphere;	G Pathway G Nitrogen was bubbled through a mixture of 1-bromo-4-methoxybenzene (5.0 g, 26.8 mmol), 3-hydroxyphenylboronic acid (6.8 g, 49.6 mmol), aqueous potassium carbonate (2 M, 20 mL, 40 mmol), acetone (170 mL) and H2O (300 mL) for 5 minutes. Pd(OAc)2 (800 mg, 3.55 mmol) was added and the mixture was stirred under a nitrogen atmosphere at room temperature for 20 minutes, after which time LC-MS analysis showed the reaction to be complete. The reaction mixture was concentrated under vacuum then diluted with ethyl acetate (200 mL). The resulting suspension was filtered through a pad of celite, and the aqueous phase was then separated and extracted with EtOAc (2×100 mL). The combined organics were dried over MgSO4, filtered and concentrated to dryness under vacuum. The crude product was loaded onto a 340 g Biotage silica cartridge and purified by Biotage chromatography (eluting with iso-hexane/EtOAc, gradient 0 to 50%). The target compound 4′-methoxy-[1,1′-biphenyl]-3-ol was isolated as a white solid (5.66 g, 78% yield).

74.8%	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In ethanol; water monomer; toluene at 80℃; for 12h;	1. 2-(2-fluoro-4-(((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)methyl)phenoxy)acetic acid (compound 17) (3-hydroxyphenyl)boronic acid (0.37 g, 2.67 mmol), 14a (0.50 g, 2.67 mmol), Pd(PPh3)4 (0.37 g, 0.32 mmol) and sodium carbonate (0.85 g, 8.02 mmol) in toluene/ethanol/H2O (35 mL, 3/1/3) was refluxed under nitrogen atmosphere for 24 h. Then the mixture was diluted with saturated ammonium chloride solution and ethyl acetate, and the insoluble material was filtered through Celite. The organic layer of the filtrate was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by column chromatography using a mixture of petroleum petroleum ether /ethyl acetate (10:1, v/v) as eluent to afford the desired product 15a 0.4 g (yield: 74.8%) as a white solid.
74.8%	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In ethanol; water monomer; toluene at 80℃; for 12h;	1. 2-(2-fluoro-4-(((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)methyl)phenoxy)acetic acid (compound 17) (3-hydroxyphenyl)boronic acid (0.37 g, 2.67 mmol), 14a (0.50 g, 2.67 mmol), Pd(PPh3)4 (0.37 g, 0.32 mmol) and sodium carbonate (0.85 g, 8.02 mmol) in toluene/ethanol/H2O (35 mL, 3/1/3) was refluxed under nitrogen atmosphere for 24 h. Then the mixture was diluted with saturated ammonium chloride solution and ethyl acetate, and the insoluble material was filtered through Celite. The organic layer of the filtrate was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by column chromatography using a mixture of petroleum petroleum ether /ethyl acetate (10:1, v/v) as eluent to afford the desired product 15a 0.4 g (yield: 74.8%) as a white solid.
69%	With palladium 10% on activated carbon; n-tetrabutylammonium fluoride trihydrate at 150℃; for 0.5h; Microwave irradiation; Inert atmosphere;

Reference： [1]Razler, Thomas M.; Hsiao, Yi; Qian, Feng; Fu, Ruiling; Khan, Rana Kashif; Doubleday, Wendel [Journal of Organic Chemistry, 2009, vol. 74, # 3, p. 1381 - 1384]
[2]Current Patent Assignee: ATXA THERAPEUTICS - WO2013/156861, 2013, A2 Location in patent: Page/Page column 35
[3]Current Patent Assignee: ATXA THERAPEUTICS - US2016/102051, 2016, A1 Location in patent: Paragraph 0094-0095
[4]Cai, Zongyu; Deng, Liming; Geng, Xinqian; Hu, Lijun; Jiao, Shixuan; Li, Zheng; Ren, Qiang; Wang, Bin; Yang, Ying; Zhang, Luyong; Zhou, Zongtao [European Journal of Medicinal Chemistry, 2022, vol. 229]
[5]Cai, Zongyu; Deng, Liming; Geng, Xinqian; Hu, Lijun; Jiao, Shixuan; Li, Zheng; Ren, Qiang; Wang, Bin; Yang, Ying; Zhang, Luyong; Zhou, Zongtao [European Journal of Medicinal Chemistry, 2022, vol. 229]
[6]Schmidt, Bernd; Riemer, Martin [Journal of Organic Chemistry, 2014, vol. 79, # 9, p. 4104 - 4118]

15
[ 13191-36-1 ]
[ 87199-18-6 ]
[ 1193524-70-7 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6724 - 6743

16
[ 23779-97-7 ]
[ 87199-18-6 ]
[ 854774-58-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 209 - 212

17
[ 21617-12-9 ]
[ 87199-18-6 ]
[ 1207842-25-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 209 - 212

18
[ 30483-75-1 ]
[ 87199-18-6 ]
[ 1233720-64-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3494 - 3505

19
[ 87199-18-6 ]
[ 836-59-9 ]
[ 1233720-65-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3494 - 3505

20
[ 87199-18-6 ]
[ 95162-14-4 ]
[ 1253690-71-9 ]

Reference： [1]Heterocycles,2010,vol. 81,p. 1509 - 1516

21
[ 76-09-5 ]
[ 87199-18-6 ]
[ 214360-76-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	In dichloromethane; at 20℃; for 48h;	To a 500 mL three-necked flask, 3-hydroxyphenylboronic acid (10.0 g, 72.46 mmol, 1.0 eq) and methylene chloride (300 mL) were added, and pinacol (10.0 g, 84.60 mmol, 1.2 eq) was added under stirring, followed by stirring at room temperature for 48 h. The reaction solution was poured into water (400 mL). The mixed solution was poured into a separatory funnel. The organic phase was separated and the aqueous phase was extracted twice with dichloromethane (400 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The crude product was purified by column chromatography (200-300 mesh silica gel, methylene chloride/methanol mixed solvent at a volume ratio of 100/1 as eluent) to obtain 15.0 g of a white solid with a yield of 94% and a purity of 97%.

Reference： [1]Patent: CN107188901,2017,A .Location in patent: Paragraph 0035; 0036
[2]Organic Letters,2010,vol. 12,p. 5474 - 5477

22
[ 16239-18-2 ]
[ 87199-18-6 ]
[ 1064680-81-4 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 534 - 547

23
[ 87199-18-6 ]
[ 612-76-0 ]
[ 108-46-3 ]

Reference： [1]European Journal of Inorganic Chemistry,2011,p. 3232 - 3239

24
[ 81971-39-3 ]
[ 87199-18-6 ]
[ 1349798-36-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7076 - 7080

25
[ 117719-17-2 ]
[ 87199-18-6 ]
[ 1252598-09-6 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 1082 - 1084

26
[ 659731-48-3 ]
[ 87199-18-6 ]
[ 1377697-97-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; ethanol; at 100℃; for 2h;	To <strong>[659731-48-3]5-chloro-2-fluoro-4-iodopyridine</strong> (516 mg, 2.004 mmol) add 3- hydroxyphenylboronic acid (498 mg, 3.61 mmol), PdC12(dppf).CH2C12 adduct (164 mg, 0.200 mmol), DME (12.5 ml), Ethanol (1.5 ml) and last add 2M sodium carbonate (3.51 ml, 7.02 mmol). The reaction was stirred at 100 C for 2 hr and followed by LCMS. The reaction was cooled, 200 ml of ethyl acetate was added, and washed with saturated sodium bicarbonate, water, saturated salt solution, dried sodium sulfate, filtered and concentrated to crude product. The crude was purified by silica gel chromatography using 40g column eluting with 0%-35% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, giving 425 mg of the titled compound as free base used without further purification. LCMS (m/z): 224.1 (MH+), rt = 0.85 min.

Reference： [1]Patent: WO2012/66065,2012,A1 .Location in patent: Page/Page column 110

27
[ 87199-18-6 ]
[ 871231-45-7 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 11667 - 11673
[2]Organic Letters,2012,vol. 14,p. 4814 - 4817,4

28
[ 97165-77-0 ]
[ 87199-18-6 ]
5-bromo-3'-hydroxybiphenyl-3-carbonitrile [ No CAS ]
C₁₉H₁₃NO₂ [ No CAS ]

Reference： [1]Chemical Biology and Drug Design,2012,vol. 80,p. 775 - 780,6

29
[ 51628-12-7 ]
[ 87199-18-6 ]
[ 1443159-80-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); potassium bromide; In 1,4-dioxane; at 85℃;Inert atmosphere;	General procedure: A stirred mixture of <strong>[51628-12-7]4-iodophenylacetonitrile</strong> (35), arylboronic acid (36-45) (1.1 equiv), Pd(PPh3)4 (0.03 equiv), KBr (1.1 equiv), and K3PO4 (2.5 equiv) in dioxane (5 mL/mmol) was purged with N2 for10 min at room temperature and then stirred overnight at 85 C under N2. The mixture was diluted with water and extracted with AcOEt. The organic phase was washed three times with water, dried (Na2SO4), and evaporated under vacuum. The residue was chromatographedon silica gel.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 63,p. 118 - 132

30
[ 87199-18-6 ]
[ 16234-15-4 ]
3-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 6h;Inert atmosphere;	General procedure: A mixture of 4 (1.5g, 5.9mmol), 4-hydroxyphenyl boronic acid (1.4g, 9.9mmol), K2CO3 (1.2g, 8.8mmol), Pd (PPh3)4 (0.2g, 0.2mmol) and DMF (20mL) was heated at 85C under nitrogen. After 6h, the reaction was was poured to H2O (30mL) and extracted with ethyl acetate. The combined organic was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The residue was recrystallized from ethanol to give a yellowed solid 5a. Yield 80%.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 358 - 365

31
[ 626-02-8 ]
[ 87199-18-6 ]
[ 612-76-0 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 4104 - 4118
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 2648 - 2659
[3]Frontiers in Immunology,2020,vol. 11

32
[ 87199-18-6 ]
[ 436799-32-5 ]
3-[6-(trifluoromethyl)pyridin-3-yl]phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86.6%	With potassium phosphate; palladium diacetate; In tetrahydrofuran; water; for 6h;Reflux;	3-hydroxyphenyl boronic acid (formula 48-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 48-B, 10 mmol, 2.26 g), potassium phosphate (25 mmol, 5.33 g), palladium acetate (0.1 mmol, 23 mg), THF (50 ml) and water (50 ml) were successively added to a 250 ml, three-necked reaction flask, heated to reflux temperature to react for 6 hours. When the reaction was finished, THF was removed by rotary evaporation and ethyl acetate (40 ml×3) was added for extraction, dried, filtered, desolventized, crystallized and dried to obtain 2.10 g of pale yellow solid, i.e. compound of formula 48-C, with the content of 98.2% (HPLC) and the yield of 86.6%.

Reference： [1]Patent: US2017/1961,2017,A1 .Location in patent: Paragraph 0034; 0035
[2]Molecular Crystals and Liquid Crystals,2015,vol. 607,p. 264 - 271

33
[ 118-72-9 ]
[ 87199-18-6 ]
3-((2,6-dimethylphenyl)thio)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With copper diacetate; triethylamine; In dichloromethane; at 0 - 5℃; for 4h;Sonication; Green chemistry;	General procedure: Naphthylboronic acid (0.25 g, 1.5 mmol) was added with 0.094 g of phenol (1.0 mmol) to 15 mL of DCM. Copper(II) acetate (0.36 g, 2.0 mmol) was then added along with triethylamine (0.5g, 5.0 mmol), and the dismembrator horn placed in the reaction vessel. The sonicator was set to 55 watts and the reaction was allowed to proceed for 4 hours (1 minute pulse with a 3 second rest). Post reaction, the product was isolated by column chromatography. Product yields were determined by weight and purity was confirmed by GC/MS and NMR.

Reference： [1]Heterocycles,2015,vol. 90,p. 271 - 297

34
[ 1532-71-4 ]
[ 87199-18-6 ]
[ 134948-98-4 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 6766 - 6769

35
[ 4295-11-8 ]
[ 87199-18-6 ]
3-(6-methylquinolin-2-yl)phenol [ No CAS ]

Reference： [1]RSC Advances,2015,vol. 5,p. 77948 - 77957

36
[ 87199-18-6 ]
[ 203436-45-7 ]
3-(2-chloro-9-isopropyl-9H-purin-6-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 70℃; for 5h;Inert atmosphere;	Step 1: synthesis of 3-(2-chloro-9-isopropyl-9H-purin-6-yl)phenol (5a)To a pre-stirred of solution of <strong>[203436-45-7]2,6-dichloro-9-isopropyl-9H-purine</strong> 3a (230 mg, 1.0 mmol), (3- hydroxyphenyl)boronic acid 4c (152 mg, 1.1 mmol) in dioxane (10 mL), were added a solution of K2C03 (345 mg, 2.5 mmol) in deionized water (1.0 mL). The mixture was degassed for 30 mm then added Pd(dppf)C12.CH2C12 (41 mg), and the resulting mixture was heated at 70C for 5 hours. LC-MS showed the reaction completed. After a simple workup, the product 5a (215 mg, 75%) was obtained by flash chromatography (silica, 20% to 50% ethyl acetate in hexanes).
75%		To a pre-stirred of solution of 2,6-dichloro-9-isopropyl-9Hpurine13a (230 mg, 1.0 mmol), (3-hydroxyphenyl)boronic acid 14a(152 mg, 1.1 mmol) in dioxane (10 mL), were added a solution of K2CO3 (345 mg, 2.5 mmol) in deionized water (1.0 mL). The mixturewas degassed for 30 min then added Pd(dppf)Cl2·CH2Cl2 (41 mg), andthe resulting mixture was heated at 70 C for 5 h. LC-MS showed the reaction completed. After a simple workup, the product 15a (215 mg,75%) was obtained by flash chromatography (silica, 20% to 50% ethylacetate in hexanes). LC-MS m/z (relative intensity): [M + H]+ 289.3(100%), 291.3 (33.5%). 1H NMR (400 MHz, CDCl3) δ 8.33 (dt, J = 7.8and 1.2 Hz, 1H), 8.24 (dd, J = 2.5 and 1.6 Hz, 1H), 8.18 (s, 1H), 7.43(t, J = 8.0 Hz, 1H), 7.04 (ddd, J = 8.1, 2.6, and 0.9 Hz, 1H), 5.92 (s,1H), 4.97 (septet, J = 6.8 Hz, 1H), 1.66 (d, J = 6.8 Hz, 6H).

Reference： [1]Patent: WO2015/137887,2015,A1 .Location in patent: Page/Page column 62; 63
[2]Bioorganic Chemistry,2020,vol. 98

37
[ 452-79-9 ]
[ 87199-18-6 ]
3-(2-fluoro-4-methylphenyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium diacetate; potassium carbonate; In 2-methoxy-ethanol; water; at 20℃; for 15h;	General procedure: To a solution of the corresponding boronic acid (1.2mmol) in EGME/H2O (3:1, 0.25M) were added Pd(OAc)2 (0.05mmol) and K2CO3 (1.2mmol), followed by the addition of the corresponding phenyl iodide (1.0mmol). The dark reaction mixture was stirred at rt for 15h, then diluted with EtOAc (40mL) and filtered through a pad of Celite. The resulting filtrate was washed with H2O (20mL) and a 1M solution of Na2SO3 (20mL). After separation, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residues were purified by column chromatography (Cy/EtOAc).

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 109,p. 216 - 237

38
[ 452-79-9 ]
[ 87199-18-6 ]
[3-(2-fluoro-4-methylphenyl)phenyl] N-hexylcarbamate [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 109,p. 216 - 237

39
[ 68162-47-0 ]
[ 87199-18-6 ]
C₁₃H₁₄B₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃;	3-Hydroxyphenylboronic acid (40 mg, 1.05 equiv) and 4-(bromomethyl)phenylboronic acid (65 mg, 1.0 equiv) were dissolved in 6 mE solution of tetrahydrothranN,Ndimethylforamide (1:1 v/v). Sodium hydride (36 mg, 5.0 equiv) is added and the reaction is allowed to stir at room temperature overnight. Water (25 mE) is then added and the reaction is acidified to pH<2 with iN HC1 and transferred to a separatory flannel. The water layer is washed with ethyl acetate (1 x75 mE) and diethyl ether (1 x75 mE). The water layer is then concentrated under vacuum to provide crude oil which is triturated with tetrahydrofuran and methanol to provide the desired boronic acid 326. [2M-3H20]=488.0 mlz. Activity: A

Reference： [1]Patent: US2015/368278,2015,A1 .Location in patent: Paragraph 1304; 1305

40
[ 41731-23-1 ]
[ 87199-18-6 ]
3-(5-methyl-1,3-thiazol-2-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation;	(3-Hydroxyphenyl) boronic acid (170 mg, 1.235 mmol), 2-bromo-5-methyl- l,3-thiazole (200 mg, 1.123 mmol), K3P04 (481 mg, 2.246 mmol) and Pd(Ph3)4 (131 mg, 0.1 12 mmol) in a mixture 3: 1 of dioxane/ water (12 mL : 4 mL) was heated in MW at 1 10 C for 30 min. The mixture was concentrated under vacuum and NaOH aq solution 1 M and DCM were added. The water was extracted several times with more DCM. The layers were separated. To the aqueous phase HC1 1M aqueous solution was added and the phase was extracted again with more DCM. The combined organics were filtered though a phase separator tube and concentrated in vacuo to give the desired product (190 mg, 0.99 mmol, Yield=75%). LC-MS (ESI): mlz (M+l)+, 191.9.

Reference： [1]Patent: WO2016/4272,2016,A1 .Location in patent: Paragraph 00958

41
[ 446273-59-2 ]
[ 87199-18-6 ]
3-(3-amino-6-chloropyridazin-4-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 110℃; for 1.5h;Inert atmosphere;	General procedure: Preparation of 6-chloro-4-arylpyridazin-3-amines Suzuki Method A mixture of sodium carbonate (336 mg, 3.17 mmol),water (5 mL) and 1,4-dioxane (15 mL) were de-gassed with nitrogen for 10 minutesand then treated with the appropriate boronic acid (199 mg, 1.63 mmol) and<strong>[446273-59-2]4-bromo-6-chloropyridazin-3-amine</strong> (330 mg, 1.58 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with dichloromethane (1:1) (129 mg, 0.16 mmol). The reaction mixturewas heated at 110 Cunder nitrogen for 90 minutes and then cooled to room temperature. The mixturewas partitioned between ethyl acetate and aq brine, the organic layer wasdried, filtered and evaporated under reduced pressure. The crude product waspurified by flash silica chromatography, see below for individual conditions.Fractions containing product were evaporated under reduced pressure to yieldthe desired target.

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 6791 - 6794

42
[ 3989-13-7 ]
[ 87199-18-6 ]
3'-((trimethylsilyl)ethynyl)-[1,1'-biphenyl]-3-ol [ No CAS ]

Reference： [1]Chinese Chemical Letters,2016,vol. 27,p. 961 - 963

43
[ 166402-16-0 ]
[ 87199-18-6 ]
3-(7-aminoquinoxalin-2-yl)phenol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 6169 - 6186

44
[ 40473-01-6 ]
[ 87199-18-6 ]
3-(3-chloro-6-pyridyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.4%	With palladium diacetate; cesium fluoride; In ethylene glycol; at -10℃; for 6h;	synthesis of 3-(3-chloro-6-pyridyl)phenol (19-C) The sequentially 1.66g (12mmol) 3-hydroxy-phenylboronic acid (19-A), 1.92g (10mmol) 2-chloro-5-bromo pyridine (19-B), 3.80g (25mmol) cesium fluoride, 45 mg (0.2mmol) palladium acetate, 50 ml of ethylene glycol added to the 250 ml three port in the reaction bottle, controls heats to -10 C reaction 6 hours. After the reaction is complete, add 40 ml × 3 ethyl acetate extraction, with 40 ml × 3 saturated salt water extraction, anhydrous magnesium sulphate drying 2 hours, filtering, desolvation, crystallization, the drying of 1.67g strawcoloured solid, i.e. compound 19-C, content 99.2% (HPLC), the yield is 80.4%.

Reference： [1]Patent: CN103910670,2016,B .Location in patent: Paragraph 0062; 0063; 0064

45
[ 87199-18-6 ]
[ 98-88-4 ]
[ 6949-73-1 ]

Reference： [1]ChemCatChem,2016,vol. 8,p. 3207 - 3212

46
[ 13195-50-1 ]
[ 87199-18-6 ]
3-(5-nitrothiophen-2-yl)phenol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 8830 - 8847

47
[ 108-86-1 ]
[ 87199-18-6 ]
[ 580-51-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate; In water; at 70℃; for 0.5h;Inert atmosphere;	General procedure: In a typical run, h-BN(at)Fur(at)Pd(OAc)2 (0.05 mmol) was added to a mixture of arylboronic acid 1 (1.0 mmol), aryl bromide 2 (1.5 mmol) and K2CO3 (1.5 mmol) in water (1 mL). The resulting mixture was stirred at 70 C under Ar protection, and the progress of the reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and the catalyst was separated. The organic phase was washed with water, dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. Finally, the residue was isolated by chromatography on a column of silica gel to afford the corresponding product 3.

Reference： [1]Advanced Synthesis and Catalysis,2017,vol. 359,p. 454 - 466
[2]Applied Organometallic Chemistry,2017,vol. 31
[3]Tetrahedron,2016,vol. 72,p. 8557 - 8564

48
[ 87199-18-6 ]
[ 175205-82-0 ]
3-(3-trifluoromethyl-2-pyridyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.6%	With palladium diacetate; potassium carbonate; In 1,4-dioxane; water; for 6h;Reflux;	3-hydroxyphenyl boronic acid (formula 86-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 86-B, 10 mmol, 2.26 g), potassium carbonate (25 mmol, 3.45 g), palladium acetate (0.5 mmol, 110 mg), dioxane (50 ml) and water (50 ml) were successively added to a 250 ml, three-necked reaction flask, heated for reflux temperature to react for 6 hours. When the reaction was finished, dioxane was removed by rotary evaporation and ethyl acetate (40 ml×3) was added for extraction, the organic phase was dried, filtered, desolventized, crystallized and dried to obtain 1.94 g of pale yellow solid, i.e. compound of formula 86-C, with the content of 99.1% (HPLC) and the yield of 80.6%.

Reference： [1]Patent: US2017/1961,2017,A1 .Location in patent: Paragraph 0038; 0039

49
[ 87199-18-6 ]
[ 175205-81-9 ]
3-(4-trifluoromethyl-2-pyridyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.5%	With palladium diacetate; cesium fluoride; In toluene; at 25℃; for 6h;	3-hydroxyphenyl boronic acid (formula 87-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 87-B, 10 mmol, 2.26 g), cesium fluoride (25 mmol, 3.80 g), palladium acetate (0.2 mmol, 45 mg), toluene (50 ml) were successively added to a 25 ml, three-necked reaction flask to react at room temperature (25° C.) for 6 hours. When the reaction was finished, the solution was extracted with ethyl acetate (40 ml×3) and water (40 ml), the organic phase was dried, filtered, desolventized, crystallized and dried to obtain 2.09 g of pale yellow solid, i.e. compound of formula 87-C, with the content of 97.8percent (HPLC) and the yield of 85.5percent.

Reference： [1]Patent: US2017/1961,2017,A1 .Location in patent: Paragraph 0042; 0043

50
[ 87199-18-6 ]
[ 175205-81-9 ]
C₂₃H₁₉F₃N₂O₄ [ No CAS ]

Reference： [1]Patent: US2017/1961,2017,A1

51
[ 22960-18-5 ]
[ 87199-18-6 ]
3-(6-fluoroquinolin-8-yl)phenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000

52
[ 917251-92-4 ]
[ 87199-18-6 ]
3-(5-(trifluoromethyl)quinolin-8-yl)phenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000

53
[ 139366-35-1 ]
[ 87199-18-6 ]
3-(5-nitroquinolin-8-yl)phenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000

54
[ 14482-51-0 ]
[ 87199-18-6 ]
C₂₂H₁₈Cl₂N₂O₄ [ No CAS ]

Reference： [1]Journal of Agricultural and Food Chemistry,2017,vol. 65,p. 6114 - 6121

55
[ 14482-51-0 ]
[ 87199-18-6 ]
C₁₁H₇Cl₂NO [ No CAS ]

Reference： [1]Journal of Agricultural and Food Chemistry,2017,vol. 65,p. 6114 - 6121

56
[ 87199-18-6 ]
[ 162102-79-6 ]
C₁₅H₁₃NO₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7267 - 7283

57
[ 585-76-2 ]
[ 87199-18-6 ]
[ 171047-01-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In 1,4-dioxane; water; at 95.0℃;Inert atmosphere;	General procedure: The halo aryl (1.0 equiv) was dissolved in a mixture of water:dioxane (1:1). The boronic acid or ester(1.5 equiv) and potassium phosphate (5.0 equiv) were added. The solution was degassed byvacuum/argon cycles (10 times) before addition of PdCl2(PPh3)2 (10 mol%) and further degassed (5times). The resulting mixture was stirred at 95 C under argon atmosphere for 16-20 hours. Thereaction mixture was filtered through Celite and diluted with water (approx. 30 mL) before washingwith chloroform (3 x 30 mL). If not stated otherwise, the aqueous phase was concentrated underreduced pressure and applied to a C18 precolumn before purification on a 10g or 60 g C18 column witha gradient of acetonitrile in water (10-100%) to yield the desired product.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 145,p. 634 - 648

58
[ 69518-17-8 ]
[ 87199-18-6 ]
C₁₄H₈N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%		Pd(PPh3)4 (45mg, OM39mmol) was added to a solution of <strong>[69518-17-8]4-iodo-phthalonitrile</strong>(lg, 3.937mmo1) in dry THF (35mL) and the reaction mixture was stirred for 20 minutes.K2C03 (544 mg, 3.937 rnmol), 3hydroxyphenylboronic acid (543 mg, 3.937 mmol) andH20 (10 mL) were added and the reaction mixture refluxed for 24 hours, after which itwas cooled to room temperature. The THF was evaporated and the resulting solidsuspended in H20 was filtered, washed with H20, redissolved in THF and dried over Na2504. After evaporation of the solvent the solid was purified by column chromatography on silica gel, using heptane/EtOAc 2:1 as eluent, yielding 1 (0.867g, 1 ,338mmo1, 34%) as a white solid.1H NMR (300 MHz, CDC13), oe (ppm): 7.98 (p, J = 9.3 Hz, 1H, H1), 7.93 - 7,83 (m,2H, H), 7.38 (d, J = 7.5 Hz, 1H, H1), 7.14 (d, J = 8.5 Hz, 1H, H), 7.05 (s, 1H, H),6.95 (d, J = 9.5 Hz, 1H, H), 4.93 (s, 1H, OH).13 NMR (300 MHz, MCOD), 6 (ppm): 141.48, 136.46, 134.14, 131.77, 123.63, 98.96.HRMS (MALDITOF, DCTB), in/z: Caic. for C14H8N2ONa: 243.0528, found 243.0524 [M+Na]

Reference： [1]Patent: WO2018/2170,2018,A1 .Location in patent: Page/Page column 32; 33

59
[ 87199-18-6 ]
[ 16097-63-5 ]
3-(2-(methylthio)-6-(trifluoromethyl)pyrimidin-4-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 5.0h;Inert atmosphere;	To a solution of 4-chloro-2- (methylthio) -6- (trifluoromethyl) pyrimidine (200mg, 0.87mmol) and (3-hydroxyphenyl) boronic acid (150mg, 1.05mmol) in DME/H2O (5mL/1mL) was added Pd (dppf) 2Cl2 (32mg, 0.04mmol) followed by Na2CO3 (280mg, 2.62mmol) under N2 atmosphere. The reaction mixture was refluxed at 110 for 5hrs. The reaction mixture was cooled to room temperature and filtered over celite. Solvents were removed in vacuo, and the residue was extracted by DCM and H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further purified by silica gel column chromatography (PE/EA30/1) to give 104mg of 3- (2- (methylthio) -6- (trifluoromethyl) pyrimidin-4-yl) phenol (71-01) as a white solid (41)

Reference： [1]Patent: WO2018/14802,2018,A1 .Location in patent: Paragraph 0277

60
[ 87199-18-6 ]
[ 405224-23-9 ]
C₁₂H₇ClN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In methanol; water; toluene;Inert atmosphere;	General procedure: <strong>[405224-23-9]5-bromo-2-chloronicotinonitrile</strong> (5, 2.16 g, 10 mmol), aromatic boronic acid (10 mmol), (PPh3)2PdCl2 (175 mg, 0.25 mmol), Na2CO3 (2.12 g, 20 mmol) were dissolved in a mixed solvent (22 mL, toluene: ethanol: water = 10: 10: 2). Nitrogen gas was bubbled through the reaction mixture for 5 min, and then the mixture was heated to 60C under inert atmosphere for 6 h. The mixture was filtered and the filtrate was concentrated under vacuum. The crude product was extracted with ethyl acetate and the organic layer was concentrated, then the solid was washed with ethyl acetate and petroleum ether to give compounds 6.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1386 - 1391

61
[ 5941-55-9 ]
[ 87199-18-6 ]
ethyl 3-(3-hydroxyphenyl)-3-ethoxypropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro(1,5-cyclooctadiene)rhodium(I) dimer; potassium hydroxide; In 1,4-dioxane; water; at 50℃; for 2h;Inert atmosphere; Sealed tube;	A mixture of (E)-<strong>[5941-55-9]ethyl 3-ethoxyacrylate</strong> (0.600 mL, 4.00 mmol), 3-hydroxyphenyl boronic acid (1.70 g, 12.0 mmol), Rh(COD)Ch (102 mg, 0.207 mmol) and potassium hydroxide (234 mg, 4.17 mmol) in 1,4-dioxane (5 mL) and water (0.5 mL) was stirred for 2 h under a nitrogen atmosphere at 50 C in a sealed tube. The reaction mixture was allowed to cool to RT and poured into 50 mL of saturated aq. H4CI, followed by extraction with ethyl acetate (3 x 50 mL). The organic layers were combined, dried over Na2S04 and concentrated. The residue obtained was purified on silica gel with ethyl acetate/petroleum ether (0-10%) to give compound 24a. Mass Spectrum (LCMS, ESI pos.): Calcd. For CisHieCU: 237.1 [M-H]+; found: 237.1.

Reference： [1]Patent: WO2018/81047,2018,A1 .Location in patent: Page/Page column 123-124

62
[ 21014-26-6 ]
[ 87199-18-6 ]
(S)-ethyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate [ No CAS ]
(R)-ethyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro(1,5-cyclooctadiene)rhodium(I) dimer; sodium hydroxide In 1,4-dioxane at 50℃; for 16h; Inert atmosphere;	36.E (E) Ethyl (,S)-3-cyclopropyl-3-(3-hydroxyphenyl)propanoate, (36e-l) and ethyl (R)-3- cyclopropyl-3-(3-hydroxyphenyl)propanoate, (36e-2) To a solution of chloro(l,5-cyclooctadiene)rhodium (I) dimer (2.46 g, 4.99 mmol) in 1,4-dioxane (50 mL) was added NaOH (aq. IN, 150 mL, 150 mmol) at RT under a nitrogen atmosphere. (3-Hydroxyphenyl)boronic acid (27.6 g, 200 mmol) was added, followed by the addition of ethyl (E)-3-cyclopropylacrylate, cpd 36d (14 g, 100 mmol) in 1,4-dioxane (50 mL). The mixture was stirred at 50 °C for 16 h. The mixture was poured into ethyl acetate/water and acidified with 2N HC1 to pH~4. The aqueous layer was extracted with ethyl acetate (2x). The combined organic layers were dried (Na2S04), filtered and concentrated. The resulting residue was first purified by flash chromatography on silica gel with EtO Ac/heptane (0-30%) to give a yellow oil, which was further purified by chiral SFC on a Chiralcel OD-H 5μιη column (250 x 30mm) using 93% CO2, 7% i- PrOH to afford compounds 36e-l ([CX]D20= +35.7 ) and 36e-2. Cpd 36e-2 : 1H NMR (CDCh) δ (ppm): 7.17 (t, J=7.8 Hz, 1H), 6.81 (d, J=7.6 Hz, 1H), 6.72 (t, J=2.0 Hz, 1H), 6.67-6.71 (m, 1H), 4.98 (s, 1H), 4.07 (qd, J=7.1, 3.5 Hz, 2H), 2.66-2.79 (m, 2H), 2.32 (dt, J=9.6, 7.6 Hz, 1H), 1.18 (t, J=7.3 Hz, 3H), 0.95-1.06 (m, 1H), 0.54-0.62 (m, 1H), 0.39-0.48 (m, 1H), 0.27 (dq, J=9.5, 4.7 Hz, 1H), 0.12-0.19 (m, 1H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2018/81047, 2018, A1 Location in patent: Page/Page column 153

63
[ 850832-54-1 ]
[ 87199-18-6 ]
methyl 4-(3-hydroxyphenyl)-5-methylisoxazole-3-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 8337 - 8352

64
[ 87199-18-6 ]
[ 139308-52-4 ]
C₁₃H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27.3%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 70℃; for 6h;	To a solution of compound 142B (3.4 g, 14.59 mmol) and (3- hydroxyphenyl)boronic acid (2.41 g, 17.51 mmol) in dioxane/H20 (50 mL/10 mL) was added K3PO4 (9.29 g, 43.77 mmol) and Pd(dppf)Cl2 (1.07 g, 1.46 mmol). The mixture was stirred at 70 C for 6 h. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was diluted with H20 (80 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10/1 to 7: 1) to give the Compound 142C (1.0 g, yield: 27.3%) was obtained as a yellow solid. 1H NMR (400MHz, CDC13) delta 8.01 - 7.87 (m, 1H), 7.36 - 7.32 (m, 1H), 7.30 - 7.26 (m, 2H), 6.90 - 6.79 (m, 1H), 5.41 - 5.30 (m, 1H), 4.24 (q, J=7.1 Hz, 2H), 3.94 (s, 3H), 1.28 (t, J=7.2 Hz, 3H). MS (ESI) m/z (M+H)+ 247.0.

Reference： [1]Patent: WO2018/9417,2018,A1 .Location in patent: Paragraph 0576

65
[ 87199-18-6 ]
[ 4027-57-0 ]
C₁₃H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25.04%	With pyridine; oxygen; copper diacetate; In dichloromethane; at 28℃; under 775.743 Torr; for 48h;Molecular sieve;	To a solution of ethyl 3-methyl-lH-pyrazole-5-carboxylate (20 g, 129.73 mmol), (3-hydroxyphenyl)boronic acid (27 g, 194.59 mmol), 4A MS (30 g) and Py (12 mL, 142.70 mmol) in DCM (500 mL) was added Cu(OAc)2 (26 g, 142.70 mmol). After addition, the reaction mixture was stirred at 28 C for 48h under 02 (15 psi) atmosphere. 100 mL of DCM was added into the reaction mixture and the mixture was filtered. The filtrate was concentrated in vacuum and the residue was dissolved into 300 mL of EtOAc. The mixture was filtered and the filtrate was concentrated in vacuum. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 5/1 to 4: 1 to 3/1) to afford compound 3 (8.0 g, yield 25.04%) as light yellow solid. 1H NMR (400MHz, DMSO-d6) delta 7.21 (t, J=7.9 Hz, 1H), 6.85 - 6.69 (m, 4H), 4.15 (q, J=7.1 Hz, 2H), 2.23 (s, 3H), 1.16 - 1.12 (m, 3H). MS (ESI) m/z (M +H)+ 246.9.

Reference： [1]Patent: WO2018/9417,2018,A1 .Location in patent: Paragraph 0569

66
[ 50-00-0 ]
[ 87199-18-6 ]
[ 1196473-37-6 ]

Yield	Reaction Conditions	Operation in experiment
25%	With trifluoroacetic acid; In chloroform; at 40℃; for 20h;Schlenk technique; Inert atmosphere; Sealed tube;	Into the Schlenk tube, add the stirring magnet, the compound 1m (138mg, 1mmol) of the above formula, and the paraformaldehyde 2 (36mg, 1.2mmol) in sequence,Under nitrogen protection, trichloromethane (10 mL) was added, and trifluoroacetic acid (297 μL, 4 mmol) was added with stirring, and then sealed, heated and stirred at 40 C for reaction for 20 hours. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography to obtain the compound of formula 3m (37 mg, 25%).

Reference： [1]Patent: CN112625056,2021,A .Location in patent: Paragraph 0092-0095

67
[ 87199-18-6 ]
[ 612-76-0 ]

Reference： [1]Organic Letters,2021,vol. 23,p. 2873 - 2877

68
[ 936-08-3 ]
[ 87199-18-6 ]
5-chloro-3'-hydroxy-[1,1'-biphenyl]-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	Stage #1: 2-bromo-4-chlorobenzoic acid; 3-hydroxyphenylboronic acid With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate In toluene for 14h; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; methanol; water monomer at 20℃;

Reference： [1]Luo, Dan; Hu, Liangzhen; Gao, Tianyong; Zhang, Xiaohui; Xiong, Yan [Journal of Organic Chemistry, 2022, vol. 87, # 8, p. 5065 - 5075]

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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. 87199-18-6 ]

Quality Control of [ 87199-18-6 ]

Related Doc. of [ 87199-18-6 ]

Product Details of [ 87199-18-6 ]

Calculated chemistry of [ 87199-18-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 87199-18-6 ]

Application In Synthesis of [ 87199-18-6 ]

[ 87199-18-6 ] Synthesis Path-Upstream 1~9

[ 87199-18-6 ] Synthesis Path-Downstream 1~68

Related Functional Groups of [ 87199-18-6 ]

Organoboron

Aryls

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 87199-18-6 ]