[ CAS No. 6272-26-0 ]

Name: 6272-26-0|6-Hydroxybenzofuran-3(2H)-one|98%
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Quality Control of [ 6272-26-0 ]

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SDS Specification

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Product Details of [ 6272-26-0 ]

CAS No. :	6272-26-0	MDL No. :	MFCD00068174
Formula :	C₈H₆O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	150.13	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 6272-26-0 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	0
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	38.23
TPSA :	46.53 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.42 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.3
Log Po/w (XLOGP3) :	1.12
Log Po/w (WLOGP) :	0.97
Log Po/w (MLOGP) :	0.12
Log Po/w (SILICOS-IT) :	1.69
Consensus Log Po/w :	1.04

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.88
Solubility :	1.98 mg/ml ; 0.0132 mol/l
Class :	Very soluble
Log S (Ali) :	-1.69
Solubility :	3.06 mg/ml ; 0.0204 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.98
Solubility :	1.56 mg/ml ; 0.0104 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.8

Safety of [ 6272-26-0 ]

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 [ 6272-26-0 ]

* 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 [ 6272-26-0 ]
Downstream synthetic route of [ 6272-26-0 ]

[ 6272-26-0 ] Synthesis Path-Upstream 1~8

1
[ 6272-26-0 ]
[ 50551-63-8 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 2013, vol. 61, # 10, p. 997 - 1001

2
[ 13196-11-7 ]
[ 6272-26-0 ]
[ 1020947-92-5 ]
[ 23681-89-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	With ammonium chloride In tetrahydrofuran; hydrogenchloride; methanol; ethyl acetate	Preparation 3 2,3-Dihydro-benzofuran-6-ol 6-Hydroxy-2H-benzofuran-3-one (3 g) was suspended in anhydrous tetrahydrofuran under an argon atmosphere and cooled to 0° C. Lithium aluminium hydride (20 ml of a 1M solution in tetrahydrofuran) was added dropwise over 10 min and the reaction allowed to reach room temperature over 2 hours. The reaction was cooled to 0° C. and treated dropwise with saturated ammonium chloride solution. Ethyl acetate (200 ml) was added and the mixture filtered through Celite. The ethyl acetate layer was separated, dried (MgSO₄) and evaporated to dryness under reduced pressure. The resulting mixture of 2,3-dihydro-benzofuran-3,6-diol and benzofuran-6-ol (approximately 1:1 by 250 MHz ¹H NMR) was dissolved in a mixture of hydrochloric acid (200 ml, 5M aqueous solution) and methanol (300 ml) and palladium hydroxide (0.5 g) added. The mixture was stirred under a hydrogen atmosphere for 3 hours then filtered through Celite. The organics were removed by evaporation under reduced pressure and the resulting solution neutralised with concentrated anmmonia solution. The product was extracted into dichloromethane. The dichloromethane solution was dried (MgSO₄) and evaporated to dryness under reduced pressure to yield the title compound (2.5 g, 92percent). ¹H NMR (250 MHz, CDCl₃) δ: 3.11 (2H, t, J=8.4 Hz), 4.57 (2H, t, J=8.4 Hz), 6.27-6.34 (2H, m), 6.92-7.02 (1H, m); m/z (API+): 139.1 (M+3H⁺).

Reference： [1] Patent: US6465493, 2002, B1,

3
[ 6272-26-0 ]
[ 23681-89-2 ]

Reference： [1] Journal of the Chemical Society, 1950, p. 3206,3212
[2] Journal of the Chemical Society, 1950, p. 3206,3212

4
[ 6272-26-0 ]
[ 13196-11-7 ]
[ 23681-89-2 ]

Reference： [1] Synthetic Communications, 2014, vol. 44, # 9, p. 1307 - 1313

5
[ 6272-26-0 ]
[ 74-88-4 ]
[ 15832-09-4 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 6 h;	General procedure: To a stirred solution of compound 3 (5 g, 33 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (13.84 g, 100 mmol), iodomethane (3.2 mL, 51 mmol) or 4-methoxybenzyl chloride (5.5 mL, 35 mmol) at 0°C. The reaction mixture was warmed slowly to r.t. and stirred for 6 h. The mixture was poured into water (100 mL) and extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with water (2 × 300 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to give compounds 5a and 5b.

Reference： [1] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6360 - 6366
[2] Tetrahedron Asymmetry, 2008, vol. 19, # 7, p. 788 - 795
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 15, p. 3226 - 3230
[4] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 15, p. 4520 - 4523
[5] Patent: WO2005/73224, 2005, A2, . Location in patent: Page/Page column 86-87
[6] European Journal of Medicinal Chemistry, 2017, vol. 130, p. 195 - 208

6
[ 6272-26-0 ]
[ 77-78-1 ]
[ 15832-09-4 ]

Yield	Reaction Conditions	Operation in experiment
72.84%	With potassium carbonate In acetone at 20℃; for 2 h;	To a solution of 1-12 (1.5 g, 10 mmol) in acetone (7 ml) was added K₂CO₃ (2.073 g, 15 mmol), followed by the addition of dimethyl sulfate (1.387 g, 11 mmol). The mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and diluted with water. The aqueous layer was extracted with dichloromethane (3 * 50 ml), dried with Na₂SO₃, and evaporated to dryness to yield 2-12 as yellow solid which was used without further purification, 72.84percent yield. M.p. 116-118 °C (Lit. m.p. 102-103 °C); ¹H NMR (CDCl₃, 500 MHz): δ 7.57 (d, J = 8.6 Hz, H4), 6.65 (dd, J1 = 2 Hz, J2 = 8.6 Hz, H5), 6.55 (d, J = 2 Hz, H7), 4.63 (s, 2H), 3.89 (s, 3H). HRMS (TOF-ES) calcd for C₉H₉O₃⁺ ([M+1]⁺): 165.0552, found 165.0535.

Reference： [1] European Journal of Medicinal Chemistry, 2015, vol. 94, p. 195 - 210
[2] Organic and Biomolecular Chemistry, 2008, vol. 6, # 19, p. 3486 - 3496

7
[ 6272-26-0 ]
[ 588703-29-1 ]

Reference： [1] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 3, p. 203 - 206
[2] Patent: WO2014/18748, 2014, A1,
[3] Patent: WO2008/141119, 2008, A2,

8
[ 6272-26-0 ]
[ 1083168-69-7 ]

Reference： [1] Patent: WO2008/141119, 2008, A2,

[ 6272-26-0 ] Synthesis Path-Downstream 1~58

1
[ 6272-26-0 ]
[ 123-08-0 ]
[ 5786-54-9 ]

Yield	Reaction Conditions	Operation in experiment
95.3%	With thionyl chloride; In ethanol; at 20℃;	In the presence of CH2Cl2 or 5N NaOH, Al2O3 in ethanol (Method A) Or in the presence of SOCl2 in EtOH (Method B)The remaining compounds (10) - (13) were synthesized according to Jayapal and Sreedhar [Int. J. Curr. Pharm. Res., 2, (2010), 60-621 (method B). For example,6-Hydroxy-3-coumaranone (3, 0.075 g, 0.5 mmol) was added to ethanol (5 mL) and an additional amount of 3-chlorobenzaldehyde (1e, 0.069 g, 0.5 mmol) was added. after,Thionyl chloride (0.054 mL, 0.75 mmol) was added dropwise at room temperature and the reaction was maintained for 2 h until precipitation occurred,Ethanol was evaporated using a rotary evaporator.Then, it was washed with cold water and cold methanol.Finally, after rotation and vacuum drying, a dark orange solid was obtained
78%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.

Reference： [1]Patent: KR2016/142676,2016,A .Location in patent: Paragraph 0061; 0098; 0099; 0100; 0133; 0134; 0159
[2]Journal of Medicinal Chemistry,2006,vol. 49,p. 329 - 333
[3]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[4]Journal of Medicinal Chemistry,2011,vol. 54,p. 5395 - 5402
[5]Journal of the Chemical Society. Perkin transactions I,1982,p. 1157 - 1162
[6]Journal of the American Chemical Society,1956,vol. 78,p. 832,837
[7]ChemBioChem,2014,vol. 15,p. 1325 - 1333

2
[ 6272-26-0 ]
[ 123-11-5 ]
[ 20727-61-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
87%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.
85%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10 mmol) or 6-hydroxy-7-methylbenzofuran-3(2H)-one (1.64 g,10 mmol) in a mixture of EtOH (10 mL) and DMF (10 mL) was treated with the appropriate aldehyde (10 mmol) and aqueous KOH solution (2.3 mL, 50%), stirred at room temperature for 4-6 h (end of reaction monitored by TLC), stirred vigorously,poured into hot H2O (50 mL), and neutralized with conc. HCl to pH 4-5. The resulting precipitate was filtered off, rinsed with H2O, dried, and recrystallized from DMF-MeOH (1:1).(2Z)-6-Hydroxy-2-(4-methoxybenzylidene)-1-benzofuran-3(2H)-one (1a). C16H12O4, yield 85%, mp 268-270 (lit. [16]: 256-258). MS(CI): 269.1 [M + H]+ (100%). 1 NMR spectrum (400 MHz, DMSO-d6, , ppm, J/Hz): 3.81 (3H,s, 4-O3), 6.70 (1H, dd, J = 8.5, 2.0, H-5), 6.77-6.81 (2H, m, H-2a, 7), 7.06 (2H, d, J = 8.4, H-3, 5), 7.60 (1H, d, J = 8.5,H-4), 7.89 (2H, d, J = 8.4, H-2, 6), 11.17 (1H, s, 6-OH).

85%	With potassium hydroxide; In ethanol; N,N-dimethyl-formamide; at 20℃;	General procedure: To a stirred solution of 0.75 g (5 mmol) 6-hydroxybenzofuranone (1) in ethanol (5 mL) and N,N-dimethylformamide (DMF) (5 mL) was added aldehyde (5 mmol) and 1.15 mLof 50% KOH. The mixture was stirred at room temperature for 4-6 h. The mixture was poured into 30 mL of hot water with vigorous stirring and neutralized with concentrated HCl at pH of 1-2. The precipitate was filtered, washed with water, dried and recrystallized from DMF-MeOH.
	With potassium hydroxide; In methanol; water; at 50 - 60℃; for 2.0h;	General procedure: To a solution of 1-12 in methanol (100 mg, 0.67 mmol, 10 ml/mmol) was added the suitably functionalized benzaldehydes (0.67 mmol), followed by a solution of KOH 50% in water (1.5 ml/mmol). The solution is heated at 50-60 C for 2-3 h. The reaction mixture was concentrated in vacuo and diluted with distilled water.The reaction mixture was adjusted to pH 7 with 1 N HCl. The aqueous layer was extracted with ethyl acetate and dried (Na2SO3).The organic phase was evaporated in vacuo to yield crude products which were subjected to column chromatography by using chloroform:methanol (8:2) to yield pure Series 1 aurones.
	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2)-one (1.50 g, 10 mmol, for the synthesis of compounds 2a-e) or 6-hydroxy-7-methylbenzofuran-3(2)-one (1.64 g, 10 mmol, for the synthesis of compounds 4a-e) and aromatic aldehyde in a 1:1 mixture of DMF-EtOH (50 ml) was treated by adding 50% aqueous solution of KOH (2.3 ml). The mixture was stirred at room temperature for 4-6 h (the completion of reaction was determined by TLC). Then the reaction mixture was poured into vigorously stirred hot H2O (50 ml) and neutralized with concentrated HCl to 4-5. The precipitate that formed was filtered off, washed with H2O, dried, and crystallized from a 1:1 mixture of DMF-MeOH.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 231 - 240
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[3]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5
[4]Chemical Papers,2018,vol. 72,p. 2443 - 2456
[5]European Journal of Medicinal Chemistry,2010,vol. 45,p. 2957 - 2971
[6]Journal of the American Chemical Society,1956,vol. 78,p. 832,837
[7]European Journal of Medicinal Chemistry,2015,vol. 94,p. 195 - 210
[8]Chemistry of Heterocyclic Compounds,2019,vol. 55,p. 212 - 216
Khim. Geterotsikl. Soedin.,2019,vol. 55,p. 212 - 216,5

3
[ 6272-26-0 ]
[ 120-14-9 ]
[ 32396-83-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
87%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10 mmol) or 6-hydroxy-7-methylbenzofuran-3(2H)-one (1.64 g,10 mmol) in a mixture of EtOH (10 mL) and DMF (10 mL) was treated with the appropriate aldehyde (10 mmol) and aqueous KOH solution (2.3 mL, 50%), stirred at room temperature for 4-6 h (end of reaction monitored by TLC), stirred vigorously,poured into hot H2O (50 mL), and neutralized with conc. HCl to pH 4-5. The resulting precipitate was filtered off, rinsed with H2O, dried, and recrystallized from DMF-MeOH (1:1).
87%	With potassium hydroxide; In ethanol; N,N-dimethyl-formamide; at 20℃;	General procedure: To a stirred solution of 0.75 g (5 mmol) 6-hydroxybenzofuranone (1) in ethanol (5 mL) and N,N-dimethylformamide (DMF) (5 mL) was added aldehyde (5 mmol) and 1.15 mLof 50% KOH. The mixture was stirred at room temperature for 4-6 h. The mixture was poured into 30 mL of hot water with vigorous stirring and neutralized with concentrated HCl at pH of 1-2. The precipitate was filtered, washed with water, dried and recrystallized from DMF-MeOH.

72%	With sodium hydroxide; In methanol; water; at 30 - 40℃;	General procedure: To a solution of substituted 6-hydroxybenzofuran-3(2H)-one (M3, S3) (3 mmol) and aldehyde derivatives (3 mmol) in methanol; NaOH solution (3 mmol in water) was added, followed by stirring at 30-40 C for 3-4 h. The reaction progress was monitored by TLC examination. After completion of the reaction, the contents were quenched with ice cold water (20 mL) and the resulting precipitate was filtered, dried and subjected to purification by flash chromatography.
50%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 231 - 240
[2]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5
[3]Chemical Papers,2018,vol. 72,p. 2443 - 2456
[4]Medicinal Chemistry,2018,vol. 14,p. 44 - 52
[5]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[6]Archives of Biochemistry,1956,vol. 60,p. 329,336

4
[ 6272-26-0 ]
[ 139-85-5 ]
sulfuretin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide In ethanol; water for 3h; Reflux;	KOH (2.00 g) in water (2.00 mL) was added to a stirred solution of 6-hydroxy-2,3-dihydrobenzo[B]furan-3-one (200 mg, 1.33 mM) and 3,4-dihydroxybenzaldehyde (219.00 mg, 1.59 mM) in ethanol (4.00 mL). Themixture was refluxed for 3 h. The resulting mixture was diluted with waterand washed with dichloromethane. 1 N-HCl was added to the aqueous phase,and the mixture was extracted with ethyl acetate. The organic phase was driedon anhydrous MgSO4, and volatiles were removed under reduced pressure.The remaining residue was purified with SiO2 chromatography to yieldsulfuretin (3) as yellow solid (305.00 mg, 85%); Rf 0.2 (ethyl acetate:nhexane= 1:1).
81%	In water for 10h; Reflux; Green chemistry;	General procedure for aurones 4a-k, 5,6. General procedure: A mixture of benzofuran-3(2H)-one (2.0 mmol), benzaldehyde (2.2mmol) and water (5 mL) was stirred at reflux temperature for 6-10 h. Completion of the reaction was checked on TLC. Then the mixture was allowed to rt and stirred for 1 h. The precipitated solids were filtered, washedwith water (2 × 5 mL) and dried to give the product.
81%	In water Reflux; Green chemistry;	Synthesis of aurones General procedure: A mixture of benzofuran-3(2H)-one (1, 2.0 mmol), aromatic aldehyde (4, 2.2 mmol) and water (5 mL) was stirred at reflux temperature for 6-10 h. Completion of the reaction was checked on TLC. Then the mixture was allowed to room temperature and stirred for 1 h. The precipitated solids were filtered, washed with water (2 × 5 mL) and dried to give the products.

60%	With hydrogenchloride In ethanol; water Reflux;	2.1.2. General Procedure for the Preparation of Substituted (Z)-2-benzylidenebenzofuran-3-ones by Acid Catalysis (3a-e) General procedure: To a solution of benzofuran-3(2H)-one derivative (2a,b,d, 1.2 mmol) in ethanol (5 ml) in the presence of corresponding benzaldehyde (1.3 mmol), aqueous solution of 5% HCl (1 ml) was added and the mixture was refluxed for 6-9 hours (controlled by TLC). After cooling in an ice bath, the solution was neutralized by adding a cold solution of 2% KOH to reach the pH of 5-6. The resulting yellow precipitate was filtered and recrystallized from diluted methanol to give the desired products. 2.1.2.1. (Z)-6-Hydroxy-2-(3,4-dihydroxybenzylidene)benzofuran-3-one (3a) Yield: 60%; orange powder; m. p.: >250 °C (280-281 °C [14]); IR (KBr): 3284 (OH), 1705 (C=O) cm-1; 1H-NMR (DMSO-d6) δ: 6.63 (s, 1H, vinylic-H) 6.70 (dd, J = 8.5, 1.7 Hz, 1H, H5), 6.76 (d, J = 1.7 Hz, 1H, H7), 6.84 (d, J = 8.2 Hz, 1H, H5′), 7.24 (dd, J = 8.2, 2.2 Hz, 1H, H6′), 7.45 (d, J = 2.2 Hz, 1H, H2′), 7.59 (d, J = 8.5 Hz, 1H, H4). Anal. Calcd for C15H10O5: C, 66.67; H, 3.73. Found: C, 66.45; H, 3.88.
26%	With potassium hydroxide In ethanol; water at 80℃;
5%	With hydrogenchloride In water; isopropyl alcohol at 80℃; for 16h;	4.1.4. General procedure of synthesis of aurones 9-15 General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.
	With hydrogenchloride
	With hydrogenchloride; acetic acid
	With hydrogenchloride; ethanol

Reference： [1]Yang, Eun-Ju; Kim, Minjun; Woo, Ji Eun; Lee, Taeho; Jung, Jong-Wha; Song, Kyung-Sik [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5639 - 5643]
[2]Venkateswarlu, Somepalli; Murty, Gandrotu Narasimha; Satyanarayana, Meka [Arkivoc, 2017, vol. 2017, # 4, p. 303 - 314]
[3]VENKATESWARLU, SOMEPALLI; MURTY, GANDROTU NARASIMHA; SATYANARAYANA, MEKA; SIDDAIAH, VIDAVALUR [Asian Journal of Chemistry, 2021, vol. 33, # 6, p. 1396 - 1402]
[4]Roshanzamir, Khashayar; Kashani-Amin, Elaheh; Ebrahim-Habibi, Azadeh; Navidpour, Latifeh [Letters in drug design and discovery, 2019, vol. 16, # 3, p. 333 - 340]
[5]Haudecoeur, Romain; Gouron, Aurelie; Dubois, Carole; Jamet, Helene; Lightbody, Mark; Hardre, Renaud; Milet, Anne; Bergantino, Elisabetta; Bubacco, Luigi; Belle, Catherine; Reglier, Marius; Boumendjel, Ahcene [ChemBioChem, 2014, vol. 15, # 9, p. 1325 - 1333]
[6]Bdzhola, V. G.; Bilokin, Y. V.; Borysenko, I. P.; Lukashov, S. S.; Protopopov, M. V.; Prykhod'ko, A. O.; Starosyla, S. A.; Vdovin, V. S.; Yarmoluk, S. M. [Bioorganic Chemistry, 2020, vol. 102]
[7]Nordstroem; Swain [Archives of Biochemistry, 1956, vol. 60, p. 329,336]
[8]Farkas et al. [Chemische Berichte, 1959, vol. 92, p. 2847,2849]
[9]Puri; Seshadri [Journal of the Chemical Society, 1955, p. 1589,1592]

5
[ 6272-26-0 ]
[ 23681-89-2 ]

Reference： [1]Journal of the Chemical Society,1950,p. 3206,3212
[2]Journal of the Chemical Society,1950,p. 3206,3212

6
[ 25015-92-3 ]
[ 6272-26-0 ]

Yield	Reaction Conditions	Operation in experiment
54%	With sodium acetate; In ethanol; at 60℃; for 5.0h;	To a solution of 2-chloro-1-(2,4-dihydroxyphenyl)ethan-1-one (160 mg, 0.86 mmol) in EtOH (5 mL), sodium acetate (85 mg, 1.03 mmol) was added. The mixture was heated to 60 C and stirred vigorously for 5 h. The solution was evaporated and water (25 mL) was added. The resulting precipitate was filtered and dried to give 70 mg (54%) of 6-hydroxybenzofuran-3(2H)-one as a white solid, m.p.: >220 C. 1H-NMR (DMSO-d6) delta 10.93 (s, 1H), 7.47 (d, J = 6.8 Hz, 1H), 6.59 (d, J = 1.6, 6.8 Hz, 1H), 6.51 (d, J = 1.5 Hz, 1H), 6.34 (d, J = 1.8 Hz, 1H), 4.71 (s, 2H). 13C-NMR (DMSO-d6) delta 197.3, 176.1, 167.2, 125.5, 113.4, 112.2, 98.8, 75.7. MS (ESI) [M - H]: 185.05.
	With sodium methylate; In methanol; for 1.66667h;Heating / reflux;	Example 2 of the invention; Synthesis of 4,6-Dihydroxybenzofuran-3(2H)-one (R1 = OH) and 6-Hydroxybenzofuran-3(2H)-one (R1 = H); [Show Image] The compounds obtained in Example 1, (R1=OH or H) are placed in suspension in methanol (100 mL). Sodium methoxide (2.5eq) is then added. The solution obtained is agitated for about 10 minutes in the cold and is then held under reflux for 1h 30. After return to ambient temperature, the medium is acidified with a solution of HCl and is evaporated. The residue obtained is taken up into ethyl acetate. The organic phase is washed with water, a saturated sodium chloride solution, is dried over sodium sulfate and is evaporated to dryness, to give the expected product as an orange powder.
		Solid NaOMe (6134 g) was added to a 0 C. solution of the chloroketone 2 (7062 g) in 49 L of methanol (MeOH) in portions over 2 h while maintaining the temperature at <20 C. The slurry was aged at room temperature for 1 h, at which time cyclization was determined to be complete by HPLC. The mixture was cooled to 0 C., and 2N HCl (49 L) was added while maintaining the temperature at <20 C. The slurry was cooled to 5-10 C., filtered, and washed first with cold 1:1 MeOH/water (5 L), and then with water (16 L). The wet filter cake was slurry washed with isopropyl alcohol (IPA) (18 L), and then was finally washed with heptane. The filter cake was then dried under a fast stream of nitrogen. Ketone 3 was isolated as a white solid.

	With sodium hydroxide; In water; at 30 - 50℃;	General procedure: 2-Chloro-1-(2,4-dihydroxyphenyl)ethanone (M2) / 2-chloro-1-(5-chloro-2,4-dihydroxyphenyl)ethanone (S2) (3mmol) was dissolved in ethanol (10 mL) with stirring, followed by the addition of NaOH solution (3 mmol of NaOH dissolved in 5 mL of water) and stirred at 50 C for 1-2 h. After completion of the reaction, ethanol was distilled off and the solid residue obtained was washed with copious amount of water. The crude product obtained was dried and recrystallized from ethanol yielding substituted 6-hydroxybenzofuran-3(2H)-one (M3, S3).
10 g	With sodium methylate; In methanol; at 20℃;Cooling with ice;	Compound 81 was dissolved in methanol; solid sodium methoxide was added portionwise in an ice bath., control temperature is less than 20 degrees, after the addition of TLC(take a small amount of reaction solution and add hydrochloric acid to acidic PE / EA = 2)The reaction was shown to be complete, ice-water bath, and 2N HCl (3.5 L) was added dropwise.The temperature is lower than 20 degrees, the mixture is cooled to 0 to 5 degrees, and the mixture is stirred for 1 / 2H.The solid was filtered off, and the toluene was taken water and dried to give 10 g of a red solid.
	With sodium acetate; In ethanol; at 78℃; for 6.0h;	(2) The crude product obtained in step (1) was dried with sodium acetate (16g) for 6 hours under anhydrous ethanol (100 mL). After the ethanol was completely distilled off, the remaining mixture was poured onto ice.Get pure6-hydroxybenzofuranone(03),As a yellow solid.

Reference： [1]Molecules,2019,vol. 24
[2]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 275 - 277
[3]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3423 - 3427
[4]Patent: EP1709964,2006,A2 .Location in patent: Page/Page column 9
[5]Patent: US2007/265332,2007,A1 .Location in patent: Page/Page column 12
[6]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6360 - 6366
[7]Journal of Medicinal Chemistry,2011,vol. 54,p. 5395 - 5402
[8]Biochimie,2010,vol. 92,p. 1180 - 1185
[9]Archiv der Pharmazie,2013,vol. 346,p. 577 - 587
[10]Medicinal Chemistry,2018,vol. 14,p. 44 - 52
[11]Patent: CN109678796,2019,A .Location in patent: Paragraph 0221; 0226; 0227; 0228
[12]Patent: CN110452231,2019,A .Location in patent: Paragraph 0030; 0038; 0050; 0053; 0058; 0061

7
[ 6272-26-0 ]
[ 459-57-4 ]
[ 139311-84-5 ]

Yield	Reaction Conditions	Operation in experiment
56%	With hydrogenchloride In ethanol at 60 - 70℃; for 3h;
	With hydrogenchloride In water; acetic acid at 20℃;	3.1. General procedure for the Synthesis of Aurones General procedure: All the aurones utilized for the glycosylation were synthesized based on the literature [10]. 0.57 mmol of benzofuranone was dissolved in 5 mL of glacial acetic acid in a 3-dram glass vial containing a magnetic stir bar in it. To this solution, 1.1 equivalent of aldehyde and 3 drops (0.1 mL) of concentrated HCl were added and stirred at room temperature for 30 min to 4 h. In most cases the reaction resulted in the precipitation of the desired product indicating completion of the reaction. After the reaction was complete, it was poured into ice-cold DI water. The precipitate obtained was filtered and washed multiple times with DI water and air dried. The resulting aurones were characterized and directly used for the glycosylation reaction. For some of the aurones which did not precipitate out efficiently, the water diluted reaction mixture was neutralized with saturated NaHCO3 and extracted with ethyl acetate.
	With potassium hydroxide In ethanol; water at 20℃;	4.1.2. General synthetic procedure for targets 1-16 General procedure: In a dry round-bottomed flask, 6-hydroxy-2,3-dihydrobenzo[b]furan-3-one (E, 1.0 equiv.) and substituted benzaldehyde (1.5equiv.), potassium hydroxide (1.0 equiv.) solved in ethanol, then themixture was reacted overnight at room temperature. After the reactionwas completed (monitored by TLC), con. hydrochloric acidwas added slowly at 0 °C. The solid was precipitated from themixture, the corresponding product F was obtained by filtration.

Reference： [1]Teo, Chin Chin; Kon, Oi Lian; Sim, Keng Yeow; Ng, Siu Choon [Journal of Medicinal Chemistry, 1992, vol. 35, # 8, p. 1330 - 1339]
[2]Kafle, Arjun; Bhattarai, Shrijana; Handy, Scott T. [Tetrahedron, 2020, vol. 76, # 43]
[3]Liu, Kai; Zhao, Xing; Qi, Xue; Hou, Dong-Liang; Li, Hao-Bin; Gu, Yu-Hao; Xu, Qing-Long [European Journal of Medicinal Chemistry, 2021, vol. 218]

8
[ 6272-26-0 ]
[ 100-52-7 ]
[ 139276-16-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium hydroxide; In water; at 20℃; for 4.0h;	General procedure: To a solution of 6-hydroxybenzofuran-3(2H)-one (134mg, 1mmol) in H2O (15mL) at room temperature was added the appropriate aldehyde (1.1mmol) and KOH 1M (2mmol). The mixture was stirred, at room temperature, for 4h. After, some drops of HCl 37% were added to the mixture until the solution reach pH 2. The mixture was extracted with ethyl acetate and combined organic layers were washed with brine, dried with anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product.
87%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: To a stirred solution of 1.5 g (10 mmol) 6-hydroxybenzofuranone(2a) in a mixture of 10 mL ethanol and 10 mL DMF wereadded appropriate aldehyde (10 mmol) and 2.3 mL of 50% aqueous solution of KOH. The mixture was stirred 4-6 h at r.t. The reactionmixture was poured into 50 mL hot water with vigorous stirringand neutralized with conc. HCl to pH 1-2. After cooling, the precipitatewas filtered, washed with water, and crystallized from mixtureDMF-MeOH with yield of 6-hydroxyaurones 3a-3c as paleyellow or yellow powders.
87%	With potassium hydroxide; In ethanol; N,N-dimethyl-formamide; at 20℃;	General procedure: To a stirred solution of 0.75 g (5 mmol) 6-hydroxybenzofuranone (1) in ethanol (5 mL) and N,N-dimethylformamide (DMF) (5 mL) was added aldehyde (5 mmol) and 1.15 mLof 50% KOH. The mixture was stirred at room temperature for 4-6 h. The mixture was poured into 30 mL of hot water with vigorous stirring and neutralized with concentrated HCl at pH of 1-2. The precipitate was filtered, washed with water, dried and recrystallized from DMF-MeOH. (2Z)-2-Benzylidene-6-hydroxy-1-benzofuran-3(2H)-one (2a)Yellow solid (87% yield); mp: 259-260 C; IR (KBr): numax 3072, 2960, 1674, 1644, 1580, 1455, 1376, 1285, 1109, 770 cm-1; 1H NMR (400 MHz, DMSO-d6): delta 6.72 (1H, dd, 3J = 8.4 Hz, 4J = 1.7 Hz, H-5), 6.78 (1H, s, H-2a), 6.80 (1H,d, 4J = 1.7 Hz, H-7), 7.38-7.53 (3H, m, H-3?, 4?, 5?), 7.63 (1H, d, 3J = 8.4 Hz, H-4), 7.94 (2H, d, 3J = 8.5 Hz, H-2?, 6?), 11.30 ppm (1H, br. s, OH-6); 13C NMR (100 MHz, DMSOd6): delta 98.71, 110.41, 112.79, 113.18, 126.08, 129.04, 129.72,131.12, 132.14, 147.45, 166.70, 168.05, 181.55 ppm; MS (CI): m/z 238.9 (MH+, 100). Anal. calcd for C15H10O3: C,75.62; H, 4.23. Found: C, 75.41; H, 4.05.

83%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide;	General procedure: Aromatic aldehyde (10 mmol)and 50% aqueous potassium hydroxide solution (2.3 ml) were added to the solution of6-hydroxybenzofuran-3-on (1.5 g, 10 mmol) in the mixture of ethanol (10 ml) and dimethylformamide(DMF) (10 ml) the mixture was stirred 4-6 hours (monitoring by TLC).Reaction mixture was precipitated in 50 ml hot water with stirring and was neutralizedby concentrated hydrochloric acid to getting pH 6-7. The precipitate was formed, andthen it was filtered and washed with water. After crystallization from methanol/DMFthe yellow or red crystalline 6-hydroxyaurones were obtained. (2Z)-2-Benzylidene-6-hydroxy-1-benzofuran-3(2H)-one. The yellow crystals wereobtained, m.p. 259-260 C, yield: 83%. 1H NMR (400 MHz, DMSO-d6), d, ppm: 6.61-6.68 (3H, m, -CCH, 2a, 7-H), 7.44(3H, m, 3, 4, 5-H), 7.55 (1H, d, 3J8.4 Hz, 4-H), 7.89 (2H, d, 3J7.5 Hz, 2, 6-H),10.98 (1H, s, 6-OH).
	With potassium hydroxide; In methanol; water; for 1.0h;Heating / reflux;	Example 3 of the invention; Synthesis of (Z)-2-Benzylidene-6-Hydroxybenzofuran-3(2H)-one : [Show Image] To the compound obtained in Example 2 and wherein R1= H (1.0 mmol), in methanol, are added, successively, a 50% solution of potassium hydroxide (1.5 mL) and benzaldehyde (1.5 eq). The solution obtained is held under reflux for 1 hour. After return to ambient temperature, the methanol is evaporated off and the residue obtained is taken up into water. The solution obtained is acidified. A precipitate appears which is recovered by filtration and washed with water. The product is obtained as an amorphous powder after silica gel column chromatography.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 80,p. 523 - 534
[2]Journal of Medicinal Chemistry,1992,vol. 35,p. 1330 - 1339
[3]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3606 - 3613
[4]Chemical Papers,2018,vol. 72,p. 2443 - 2456
[5]Molecular Crystals and Liquid Crystals,2018,vol. 672,p. 11 - 17
[6]European Journal of Medicinal Chemistry,2010,vol. 45,p. 2957 - 2971
[7]Journal of Medicinal Chemistry,2006,vol. 49,p. 329 - 333
[8]Patent: EP1709964,2006,A2 .Location in patent: Page/Page column 9-10
[9]ChemBioChem,2014,vol. 15,p. 1325 - 1333
[10]ChemMedChem,2019,vol. 14,p. 1537 - 1546

9
[ 6272-26-0 ]
[ 100-39-0 ]
[ 139149-21-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 18.0h;	Commercial 6-hydroxy-2H-benzofuran-3-one (4.4 g, 29.3 [MMOL)] was dissolved in 50 mL dry DMF and potassium carbonate (7.36 g, 53.3 [MMOL)] was added, followed by slow addition of benzyl bromide (3.8 mL, 32.0 [MMOL).] The reaction was stirred at rt for 18 h, filtered, and the filtrate poured into 250 mL cold water. The red solid obtained was filtered, washed with water, and dried to give 7.0 g (98%) product, with properties matching the literature (see, e. g. , J. Med. Chem. 39: 5035,1996).
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18.0h;	Intermediate-51 : 6-(Benzyloxy)benzofuran-3(2H)-one:Commercially available 6-hydroxy-2H-benzofuran-3-one (4.4 g, 29.3 mmol) was dissolved in 50 mL dry DMF and potassium carbonate (7.36 g, 53.3 mmol) was added, followed by slow addition of benzyl bromide (3.8 mL, 32.0 mmol). The reaction was stirred at room temperature for 18 h, filtered, and the filtrate poured into 250 mL cold water. The red solid obtained was filtered, washed with water, and dried to give 7.0 g (98 %). GCMS: 239.91 (M+).
95%	With potassium carbonate; In N,N-dimethyl-formamide;	b 6-Benzyloxy-2,3-dihydro-3-oxo-benzofuran To a stirred solution of 6-hydroxy-3-oxo-2,3-dihydrobenzofuran of Example 6(a) (32 kg, 213 moles) in DMF (192 L) was added potassium carbonate (31.0 kg, 224 moles). After stirring for 5 min. at room temperature, benzyl bromide (145.2 kg, 264 moles) was added and the resulting mixture was stirred for 2 hours at room temperature. The mixture was poured into water (651 L), stirred for 30 minutes and the product collected by centrifugation. The crude solid was washed with water (580 L), 80% ethanol (100 L) and dried under vacuum to afford the desired product (49.1 kg; 95%) which was used without any further purification.

95%	With potassium carbonate; In N,N-dimethyl-formamide;	b 6-Benzyloxy-2,3-dihydro-3-oxo-benzofuran To a stirred solution of 6-hydroxy-3-oxo-2,3-dihydrobenzofuran of Example 10(a) (32 kg, 213 moles) in DMF (192 L) was added potassium carbonate (31.0 kg, 224 moles). After stirring for 5 min. at room temperature, benzyl bromide (45.2 kg, 264 moles) was added and the resulting mixture was stirred for 2 hours at room temperature. The mixture was poured into water (651 L), stirred for 30 minutes and the product collected by centrifugation. The crude solid was washed with water (580 L), 80% ethanol (100 L) and dried under vacuum to afford the desired product (49.1 kg, 95%) which was used without any further purification.
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.0h;	To 6-hydroxyl-2, 3-dihydrobenzofuran-3-one (30 g, 200 mmol) in DMF (600 mL) was added K2CO3 (220 mmol, 30.4 g) followed by BnBr (200 mmol, 24 mL). After stirring at room temperature for 3 hours, the reaction mixture was partitioned between methyl /-butyl ether (MTBE, 500 mL) and water (IL). The aqueous layer was separated and further extracted with MTBE (2 x 500 mL). The organic layers were combined, washed with water (500 mL), Brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give 6 as a yellow solid. LC-MS for C15Hi3O3 [M+H+]: calculated 241.1, found 241.1.
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.0h;	To 6-hydroxyl-2, 3-dihydrobenzofuran-3-one (30 g, 200 mmol) in DMF (600 mL) was added K2CO3 (220 mmol, 30.4 g) followed by BnBr (200 mmol, 24 mL). After stirring at room temperature for 3 EPO <DP n="28"/>hours, the reaction mixture was partitioned between methyl t-butyl ether (MTBE, 500 mL) and water (IL). The aqueous layer was separated and further extracted with MTBE (2 x 500 mL). The organic layers were combined, washed with water (500 mL), Brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give 6 as the product yellow solid. LC-MS for C 15Hl 303 [M+H]: calculated 241, found 241.
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.0h;	To 6-hydroxyl-2, 3-dihydrobenzofuran-3-one (30 g, 200 mmol) in DMF (600 mL) was added K2CO3 (220 mmol, 30.4 g) followed by benzyl bromide (BnBr) (200 mmol, 24 mL). After stirring at room temperature for 3 hours, the reaction mixture was partitioned between methyl t-butyl ether (MTBE, 500 mL) and water (IL). The aqueous layer was separated and further extracted with MTBE (2 x 500 mL). The organic layers were combined, washed with water (500 mL), Brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the desired compound. LC-MS calculated forC15H13O3 [M+H]: 241, found 241.

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 5385 - 5391
[2]Patent: WO2004/11446,2004,A1 .Location in patent: Page 166
[3]Patent: WO2012/49555,2012,A1 .Location in patent: Page/Page column 73
[4]Patent: US5663368,1997,A
[5]Patent: US5663368,1997,A
[6]MedChemComm,2015,vol. 6,p. 1293 - 1302
[7]Journal of Medicinal Chemistry,1996,vol. 39,p. 5035 - 5046
[8]Patent: WO2006/83781,2006,A1 .Location in patent: Page/Page column 44
[9]Patent: WO2008/54674,2008,A2 .Location in patent: Page/Page column 26-27
[10]Patent: WO2008/54675,2008,A2 .Location in patent: Page/Page column 22
[11]Drug Design, Development and Therapy,2015,vol. 9,p. 5479 - 5489

11
[ 6272-26-0 ]
[ 100-83-4 ]
[ 61429-80-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.
	With hydrogenchloride; In methanol; water;	EXAMPLE 1 Synthesis of 2-[(3-hydroxyphenyl)methylene]-<strong>[6272-26-0]6-hydroxy-3(2H)-benzofuranone</strong> After 6-hydroxy-2H-benzofuran-3-one 1 g and 3-hydroxybenzaldehyde 0.813 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for two hours. The solution was cooled to room temperature, water 400 ml was added and allowed to stand for one hour. Precipitated crystals were filtered. The crystals were dried over phosphorous pentoxide at a temperature of 60 C. for five hours under reduced pressure to obtain the desired compound 1.20 g. FAB MASS; 255 (M+1) 1 H-NMR (ppm, in DMSO-d6); 6.67 (1H, s), 6.71 (1H, dd, J=8.5, 1.8 Hz), 6.77 (1H, d, J=1.8 Hz), 6.83 (1H, ddd, J=8.0, 2.5, 0.9 Hz), 7.27 (1H, t, J=8.0 Hz), 7.26 (1H, d, J=9.4 Hz), 7.38 (1H, t, J=2.1, 2.1 Hz), 7.62 (1H, d, J=9.6 Hz), 9.64 (1H, s), 11.20 (1H, s)

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5395 - 5402
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[3]Patent: US6143779,2000,A
[4]ChemBioChem,2014,vol. 15,p. 1325 - 1333

12
[ 6272-26-0 ]
[ 18162-48-6 ]
[ 299912-77-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With 1H-imidazole; In dichloromethane; at 20℃; for 3.0h;	G. 2-(2,3-Dihvdrobenzofuran-6-yl)acetonitrile; Step a: 6-(tert-Butyldimethylsilyloxy)benzofuran-3(2H)-one; To a solution of 6-hydroxybenzofuran-3(2H)-one (30.0 g, 200 mmol) in dichloromethane (500 mL) was added TBSCl (36.0 g, 240 mmol) and imidazole (16.3 g, 240 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 h. The solvent was removed under reduced pressure to afford 6-(tert- butyldimethylsilyloxy)benzofuran-3(2H)-one (40.0 g, 80% yield), that was used directly in the next step without further purification.
79%	With triethylamine; In acetone;	[00132] The benzofuranyl carbonyl moiety was prepared by protecting the hydroxyl groupof compound 13 by reacting with tert-butyldimethylsilyl chloride (1.0 equivalents) andtriethylamine (TEA, 1.1 equivalents) in acetone, to give compound 14 in 79% yield. A solutionof compound 14 in methanol was then treated with sodium borohydride (1.0 equivalent) at roomtemperature overnight. The reaction was quenched with an addition of acetone, stirred at roomtemperature for a further 2.5 hours, aqueous HC1 (4N) was added with the temperature controlledto below 28 C, tetrahydrofuran (THF) was added, and the solution stirred overnight under argonand in the absence of light. The product, compound 15, was isolated quantitatively by extractioninto methylene chloride, concentrated at low heat, and used without further purification. Thetriflate ester, compound 16, was produced in 69% yield from compound 15 by reacting it with Nphenyl-bis(trifluoromethanesulfonimide) (1.0 equivalent) in methylene chloride for 72 hours.Compound 16 in a mixture of DMF, methanol, and triethylamine, was added to a preparedsolution of palladium acetate, 1,3-Bis(diphenylphosphino)propane (dppp), DMF and methanol inan autoclave. Carbon monoxide was charged into the autoclave to a pressure of 8 bar, and the reaction mixture was heated at 70 C for 6 hours. After workup, compound 17 was isolated in 91% yield. Lithium hydroxide (4 equivalents) in methanol and water was used to hydrolyze the ester and permit the isolation of compound 18? in 97% yield.
70%	With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 20℃;	To a solution of 100 mmol of commercially available 6-hydroxy- [2H]- benzofuran-3-one (compound 1.8) and 150 mmol of imidazole in 300 mL of dry DMF was added 110 mmol of tert-butyldimethylsilylchloride ("TBDMSC1") at room temperature, the resulting mixture was stirred at room temperature overnight. The solvent was removed, and the residue was diluted with 100 mL of EtOAc, washed with saturated aqueous NH4C1, and dried with anhydrous Na2S04. The solvent was removed, and the residue was purified to give corresponding intermediate in 70% yield. ESI-MS (m/z) : (M+H+) 265. 1.

	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 2.0h;	To a stirred solution of 6-hydroxy-2,3-dihydrobenzofuran-3-one (30 g, 0.2 mol) in DMF (375 mL) was added tert-butyldimethylsilyl chlroride (39.2 g, 0.26 mol) and triethylamine (42 mL, 0.3 mol). The mixture was stirred at room temperature for 2 h. It was then diluted with diethyl ether (1.5 L), washed with ammonium chloride (750 mL, aq. sat.) and brine (450 mL), dired over magnesium sulfate, filtered and concentrated. The crude product was purified on a Biotage 65i silica gel column, eluding with ethyl acetate and hexanes (3:7). The final productproduct was collected as yellow solid.
5.23 g	With 1H-imidazole; In tetrahydrofuran; at 0 - 20℃; for 4.0h;	To a solutionof 6-hydroxy-[2H]-benzofuran-3-one (17) (3.0 g, 20.0 mmol) in THF (60 mL)at 0C was added imidazole (2.0 g, 30.0 mmol) and tert-butyldimethylsilyl chloride (4.5 g, 30.0 mmol). After stirringat room temperature for 4 h, the solution was filtered, and the filtrate wasconcentrated to give a crude, the crude was purified by column chromatographyto get the product 31 (5.23 g) as ayellow oil. Yield 99%; 1H NMR (500 MHz, CDCl3) delta 7.56 (d, J = 8.5 Hz, 1H), 6.59(dd, J = 8.5, 2.0 Hz, 1H), 6.53 (d, J = 1.9 Hz, 1H), 4.63 (s,2H), 1.01 (s, 9H), 0.28 (s, 6H).
	With 1H-imidazole; In dichloromethane; at 20℃; for 0.08333330000000001h;Cooling with ice;	Compound 82 was added to dichloromethane and was not completely dissolved.Imidazole was added under ice water bath. Then add TBSCl in batches, the temperature is within 20 degrees, and after 5 minutes, TLC shows complete.After quenching with water, the mixture was extracted with dichloromethane and dried.The concentrated product is directly subjected to the next step of the reaction.

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 5803 - 5806
[2]Patent: WO2008/141119,2008,A2 .Location in patent: Page/Page column 77
[3]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[4]Patent: WO2014/18748,2014,A1 .Location in patent: Paragraph 00131; 00132; 00133; 00134; 00135
[5]Patent: WO2005/44817,2005,A1 .Location in patent: Page/Page column 80
[6]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837
[7]Patent: US2007/265332,2007,A1 .Location in patent: Page/Page column 11
[8]Tetrahedron Letters,2015,vol. 56,p. 4383 - 4387
[9]Patent: CN109678796,2019,A .Location in patent: Paragraph 0021; 0229; 0230; 0231

13
[ 6272-26-0 ]
[ 13196-11-7 ]

Yield	Reaction Conditions	Operation in experiment
		Acetic acid (HOAc) (3.11 L, 3 equivalents) was added to a slurry of NaBH4 (1368 g) in 41.0 L of tetrahydrofuran (THF) at 23 C. over 6 h. Vigorous gas evolution occurred, and an ice/water bath was used to maintain the temperature at <30 C. The mixture was maintained for at least 8 h at ambient temperature. Ketone 3 (2715 g, 1 equivalent) was added as a solid in portions over 1 h to minimize gas evolution, and an ice/water bath was used to keep the temperature at <30 C. The resulting mixture was aged at room temperature for 6 h. Water (6 L) was added over 2 h with cooling so that the temperature was maintained at <30 C. Vigorous gas evolution occurred, especially early in the water addition. The slurry became thick during the water addition. To the slurry was added 5N HCl (5 L) over 1 h, and the mixture was aged for 0.5 h. Elimination was assayed as complete by HPLC. The reaction mixture was transferred to a 100 L extraction vessel, and 26 L of methyl t-butyl ether (MTBE) and 17 L of water were added. Then 10 N NaOH (5 L) was added, and the mixture was mixed vigorously. The dark aqueous layer (pH 9) was separated. The organic layer was washed with 10 wt. % Na2CO3 (5 L). The pH of the aqueous wash was 10. The organic layer was then washed with 20% brine (5 L). The organic layer was concentrated on a rotary evaporator, and was then rinsed from the flask with toluene (6 L). Toluene (4 L) was then added, and the resulting thin slurry was filtered to remove impurities. The filtrate was concentrated on a rotary evaporator to an oil that eventually solidified to 1-benzofuran-6-ol 4 as a pale orange solid.
	With sodium tetrahydroborate;	Benzen-1,3-diolwas treated with chloroacetonitrile in the presence of HClto give 6-hydroxy-coumaran-3-one. This compound was reducedwith NaBH4 and dehydrated by acid to give 6-hydroxybenzofuran.Compound 1017) was obtained by methylation ofalcohol described as compound 4. Compound 10 was obtainedby methylation of alcohol described as compound 4. Colorlessoil, 1H-NMR (500 MHz, CDCl3) delta: 3.72 (3H, s), 6.58 (1H, d,J=1.7 Hz), 6.77 (1H, dd, J=2.3, 8.6 Hz), 6.94 (1H, d, J=2.3 Hz),7.34 (1H, d, J=8.6 Hz), 7.43 (1H, d, J=1.7 Hz). 13C-NMR(125 MHz, CDCl3) delta: 55.7, 96.0, 106.5, 112.1, 120.8, 121.3,144.2, 156.1, 158.2. Its spectral data are in accordance withpreviously reported data.
	With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 20℃; for 16h;	To a solution of Example 5a (1.5 g, 10.0 mol, 1.0 eq) in THF (20 mL) was added 5 mL BH3Me2S (1OM, 0.5 mol, 5 eq) at ice temperature (0 C), the mixture was then turned to room temperature and stirred for another 16 hrs. The reaction was quenched by adding 40 mL of methanol. The solvent was then removed, and the residue was further purified by flash chromatography, eluting with 40%-70% of EtOAc in Petroleum Ether, to give the desired product (Example Sb, 0.26 g, crude yield21%) as yellow solid. MS [M+1jb 135.1

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837
[2]Tetrahedron Letters,2000,vol. 41,p. 5803 - 5806
[3]Patent: US2007/265332,2007,A1 .Location in patent: Page/Page column 12
[4]Patent: WO2014/18748,2014,A1
[5]Chemical and Pharmaceutical Bulletin,2013,vol. 61,p. 997 - 1001
[6]Patent: WO2017/218960,2017,A1 .Location in patent: Paragraph 00395
[7]Patent: WO2008/141119,2008,A2
[8]Patent: CN109678796,2019,A

14
[ 6272-26-0 ]
[ 74-88-4 ]
[ 15832-09-4 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 6h;	General procedure: To a stirred solution of compound 3 (5 g, 33 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (13.84 g, 100 mmol), iodomethane (3.2 mL, 51 mmol) or 4-methoxybenzyl chloride (5.5 mL, 35 mmol) at 0C. The reaction mixture was warmed slowly to r.t. and stirred for 6 h. The mixture was poured into water (100 mL) and extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with water (2 × 300 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to give compounds 5a and 5b.
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 48h;	Example 151; 6- ( (6, 7-bis (Methoxy)-4-quinolinyl) oxy)-N- (4-chlorophenyl)-1- benzofuran-3-carboxamide; Step (a) Preparation of 6-methoxybenzofuran-3 (2R)-one; 6-Hydroxybenzofuran-3 (2H)-one (6 g, 40.0 mmol) was dissolved in DMF (80 mL), then added potassium carbonate (6.07 g, 43.97 mmol) and methyl iodide (4.12 mL, 65.95 mmol). The reaction was stirred at RT for 2 days. The mixture was filtered and the filtrate was concentrated in vacuo. The remaining oil was dissolved in EtOAc and washed with water. The aqueous layer was back-extracted with EtOAc (2x). The organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The remaining orange-red solid was purified by silica gel chromatography (1: 4 EtOAc/hexane) to afford 6-methoxybenzofuran-3 (2H)-one as a bright yellow crystalline solid. MS (ESI, pos. ion) m/z : 165.1 (M+1).

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6360 - 6366
[2]Tetrahedron Asymmetry,2008,vol. 19,p. 788 - 795
[3]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3226 - 3230
[4]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[5]Patent: WO2005/73224,2005,A2 .Location in patent: Page/Page column 86-87
[6]European Journal of Medicinal Chemistry,2017,vol. 130,p. 195 - 208

15
[ 288-32-4 ]
[ 6272-26-0 ]
[ 18162-48-6 ]
[ 374890-59-2 ]
[ 299912-77-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium chloride; sodium hydrogencarbonate; In N,N-dimethylformamide (DMF);	Example 1 Preparation of 3-[6-(4-methoxyphenyl)benzo[b]furan-3-yl] Pyridine t-butyldimethylchlorosilane (3.6 g, 23.88 mmol) was added to a solution of 6-hydroxy-2,3-dihydrobenzo[b]furan-3-one (3.0 g, 19.98 mmol) and imidazole (2.0 g, 29.38 mmol) in N,N-dimethylformamide (DMF) (30 ml) under cooling with ice. The mixture was warmed to room temperature and stirred for 40 minutes. The reaction mixture was concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate, washed with water, with diluted hydrochloric acid, with saturated aqueous solution of sodium bicarbonate, and then with saturated brine (aqueous solution of sodium chloride), sequentially, and dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The oily residue obtained was charged to silica gel column chromatography (hexane:ether=3:1) to obtain a yellow waxy product of 6-t-butyldimethylsilyloxy-2,3- dihydrobenzo[b]furan-3-one (4.3 g, 82%). 1H-NMR (CDCl3) delta: 0.24(s, 6H), 0.97(s, 9H), 4.59(s, 2H), 6.49(d, J=1.8 Hz, 1H), 6.54(dd, J=1.8, 8.5 Hz, 1H), 7.52(d, J=8.5 Hz, 1H).

Reference： [1]Patent: US2003/149079,2003,A1

16
[ 13196-11-7 ]
[ 6272-26-0 ]
[ 1020947-92-5 ]
[ 23681-89-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	With ammonium chloride;palladium dihydroxide; In tetrahydrofuran; hydrogenchloride; methanol; ethyl acetate;	Preparation 3 2,3-Dihydro-benzofuran-6-ol 6-Hydroxy-2H-benzofuran-3-one (3 g) was suspended in anhydrous tetrahydrofuran under an argon atmosphere and cooled to 0° C. Lithium aluminium hydride (20 ml of a 1M solution in tetrahydrofuran) was added dropwise over 10 min and the reaction allowed to reach room temperature over 2 hours. The reaction was cooled to 0° C. and treated dropwise with saturated ammonium chloride solution. Ethyl acetate (200 ml) was added and the mixture filtered through Celite. The ethyl acetate layer was separated, dried (MgSO4) and evaporated to dryness under reduced pressure. The resulting mixture of 2,3-dihydro-benzofuran-3,6-diol and benzofuran-6-ol (approximately 1:1 by 250 MHz 1H NMR) was dissolved in a mixture of hydrochloric acid (200 ml, 5M aqueous solution) and methanol (300 ml) and palladium hydroxide (0.5 g) added. The mixture was stirred under a hydrogen atmosphere for 3 hours then filtered through Celite. The organics were removed by evaporation under reduced pressure and the resulting solution neutralised with concentrated anmmonia solution. The product was extracted into dichloromethane. The dichloromethane solution was dried (MgSO4) and evaporated to dryness under reduced pressure to yield the title compound (2.5 g, 92percent). 1H NMR (250 MHz, CDCl3) delta: 3.11 (2H, t, J=8.4 Hz), 4.57 (2H, t, J=8.4 Hz), 6.27-6.34 (2H, m), 6.92-7.02 (1H, m); m/z (API+): 139.1 (M+3H+).

Reference： [1]Patent: US6465493,2002,B1

17
[ 6272-26-0 ]
[ 591-31-1 ]
(2Z)-6-hydroxy-2-(3-methoxybenzylidene)-1-benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.
79%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10 mmol) or 6-hydroxy-7-methylbenzofuran-3(2H)-one (1.64 g,10 mmol) in a mixture of EtOH (10 mL) and DMF (10 mL) was treated with the appropriate aldehyde (10 mmol) and aqueous KOH solution (2.3 mL, 50%), stirred at room temperature for 4-6 h (end of reaction monitored by TLC), stirred vigorously,poured into hot H2O (50 mL), and neutralized with conc. HCl to pH 4-5. The resulting precipitate was filtered off, rinsed with H2O, dried, and recrystallized from DMF-MeOH (1:1).
61%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.

With hydrogenchloride; In methanol;

EXAMPLE 10 Synthesis of 2-[(3-methoxyphenyl)methylene]-<strong>[6272-26-0]6-hydroxy-3(2H)-benzofuranone</strong> After 6-hydroxy-2H-benzofuran-3-one 1 g and 3-methoxybenzaldehyde 1.125 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60 C. for four hours under reduced pressure to obtain the desired compound 1.22 g. FAB MASS; 269 (M+1) 1 H-NMR (ppm, in DMSO-d6); 3.78 (3H, s), 6.70 (1H, dd, J=8.8, 2.1 Hz), 6.72 (1H, s), 6.78 (1H, d, J=2.2 Hz), 6.97 (1H, dd, J=8.2, 2.4 Hz), 7.36 (1H, t, J=7.9 Hz), 7.46 (1H, m), 7.51 (1H, d, J=7.6 Hz), 7.60 (1H, d, J=8.5 Hz), 11.18 (1H, s)

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[2]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5
[3]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 231 - 240
[4]European Journal of Medicinal Chemistry,2010,vol. 45,p. 2957 - 2971
[5]Patent: US6143779,2000,A

18
[ 6272-26-0 ]
[ 93-02-7 ]
(Z)-2-(2,5-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride In ethanol; water at 60 - 70℃;	4.2.12 4.2.7. (Z)-6-Hydroxy-2-(2-methoxybenzylidene)benzofuran-3(2H)-one (9a) General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 °C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
62%	With sodium hydroxide In methanol; water at 30 - 40℃;	3.1.3. General Procedure for Synthesis of Substituted 2-aryl/heteroarylidene-6-hydroxy benzofuran-3(2H)-one(SY1-SY10) General procedure: To a solution of substituted 6-hydroxybenzofuran-3(2H)-one (M3, S3) (3 mmol) and aldehyde derivatives (3 mmol) in methanol; NaOH solution (3 mmol in water) was added, followed by stirring at 30-40 °C for 3-4 h. The reaction progress was monitored by TLC examination. After completion of the reaction, the contents were quenched with ice cold water (20 mL) and the resulting precipitate was filtered, dried and subjected to purification by flash chromatography.
	With hydrogenchloride In methanol; water	6 Synthesis of 2-[(2,5-dimethoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone EXAMPLE 6 Synthesis of 2-[(2,5-dimethoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and 2,5-dimethoxybenzaldehyde 1.23 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, water 400 ml was added and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60° C. for four hours under reduced pressure to obtain the desired compound 1.21 g. FAB MASS; 299 (M+1) 1 H-NMR (ppm, in DMSO-d6); 3.76 (3H, s), 3.82 (3H, s), 6.71 (1H, dd, J=8.5, 1.8 Hz), 6.78 (1H, d, J=1.8 Hz), 6.99 (3H, m), 7.59 (1H, d, J=8.5 Hz), 7.66 (1H, d, J=2.7 Hz), 11.16 (1H, s)

Reference： [1]Lee, Young Hun; Shin, Min Cheol; Yun, Yong Don; Shin, Seo Young; Kim, Jong Min; Seo, Jeong Moo; Kim, Nam-Jung; Ryu, Jong Hoon; Lee, Yong Sup [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 1, p. 231 - 240]
[2]Kadasi, Sundeep; Costa, Thadeu E.M.M.; Arukala, Neha; Toshakani, Mallika; Duggineti, Chaitanya; Thota, Sreekanth; Gupta, Sayan D.; Raj, Shiva; Penido, Carmen; Henriques, Maria G.; Raghavendra, Nulgumnalli M. [Medicinal Chemistry, 2018, vol. 14, # 1, p. 44 - 52]
[3]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6143779, 2000, A

19
[ 6272-26-0 ]
[ 60186-33-6 ]
2-[(3-ethoxy-4-benzyloxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In methanol;	EXAMPLE 17 Synthesis of 2-[(3-ethoxy-4-benzyloxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and <strong>[60186-33-6]3-ethoxy-4-benzyloxybenzaldehyde</strong> 1.80 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60 C. for four hours under reduced pressure to obtain the desired compound 1.33 g. FAB MASS; 389 (M+1) 1H-NMR (ppm, in DMSO-d6); 1.34 (3H, t), 4.08 (3H, s), 5.14 (2H, s), 6.70-6.73 (3H, m), 6.79 (1H, s), 7.08 (1H, d, J=8.5 Hz), 7.39-7.60 (8H, m), 11.11 (1H, s)

Reference： [1]Patent: US6143779,2000,A

20
[ 6272-26-0 ]
[ 15174-69-3 ]
2-[(3-methyl-4-hydroxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In methanol; water	23 Synthesis of 2-[(3-methyl-4-hydroxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone EXAMPLE 23 Synthesis of 2-[(3-methyl-4-hydroxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and 3-methyl-4-hydroxybenzaldehyde 1.00 g were dissolved in methanol 70 ml, concentrated hydrochloric acid 60 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and water 250 ml was added. Precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60° C. for four hours under reduced pressure to obtain the desired compound 1.22 g. FAB MASS; 268 (M+1) 1 H-NMR (ppm, in DMSO-d6); 2.18 (3H, s), 6.65 (1H, s), 6.76 (1H, dd, J=8.5, 1.8 Hz), 6.76 (1H, d, J=1.8 Hz), 7.90 (1H, d, J=8.8 Hz), 7.57 (1H, d, J=8.5 Hz), 7.66 (2H, m)

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6143779, 2000, A

21
[ 6272-26-0 ]
[ 32723-67-4 ]
2-[(3-methyl-4-methoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In methanol	19 Synthesis of 2-[(3-methyl-4-methoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone EXAMPLE 19 Synthesis of 2-[(3-methyl-4-methoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and 3-methyl-4-methoxybenzaldehyde 1.11 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60° C. for four hours under reduced pressure to obtain the desired compound 0.75 g. FAB MASS; 283 (M+1) 1 H-NMR (ppm, in DMSO-d6); 2.18 (3H, s), 3.83 (3H, s), 6.68 (1H, s), 6.70 (1H, dd, J=8.5, 2.6 Hz), 7.03 (1H, d, J=8.5 Hz), 7.58 (1H, d, J=8.2), 7.71 (1H, d, J=2.1 Hz), 7.78 (1H, dd, J=8.5, 1.8 Hz), 11.11 (1H, s)

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6143779, 2000, A

22
[ 6272-26-0 ]
[ 7311-34-4 ]
(Z)-2-(3,5-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With hydrogenchloride In ethanol; water at 60 - 70℃;	4.2.14 4.2.7. (Z)-6-Hydroxy-2-(2-methoxybenzylidene)benzofuran-3(2H)-one (9a) General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 °C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
67%	With hydrogenchloride In ethanol; water at 60 - 70℃;	General procedure A for the synthesis of aurones: General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 °C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.
	With hydrogenchloride In methanol	5 Synthesis of 2-[(3,5-dimethoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone EXAMPLE 5 Synthesis of 2-[(3,5-dimethoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and 3,5-dimethoxybenzaldehyde 1.23 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60° C. for four hours under reduced pressure to obtain the desired compound 1.42 g. FAB MASS; 299 (M+1) 1 H-NMR (ppm, in DMSO-d6); 3.77 (6H, s), 6.55 (1H, m), 6.67 (1H, s), 6.71 (1H, dd, J=8.5, 2.1 Hz), 6.79 (1H, d, J=2.1 Hz), 7.09 (2H, d, J=2.1 Hz), 7.59 (1H, d, J=8.2 Hz)

With hydrogenchloride In water; acetic acid at 20℃;

3.1. General procedure for the Synthesis of Aurones General procedure: All the aurones utilized for the glycosylation were synthesized based on the literature [10]. 0.57 mmol of benzofuranone was dissolved in 5 mL of glacial acetic acid in a 3-dram glass vial containing a magnetic stir bar in it. To this solution, 1.1 equivalent of aldehyde and 3 drops (0.1 mL) of concentrated HCl were added and stirred at room temperature for 30 min to 4 h. In most cases the reaction resulted in the precipitation of the desired product indicating completion of the reaction. After the reaction was complete, it was poured into ice-cold DI water. The precipitate obtained was filtered and washed multiple times with DI water and air dried. The resulting aurones were characterized and directly used for the glycosylation reaction. For some of the aurones which did not precipitate out efficiently, the water diluted reaction mixture was neutralized with saturated NaHCO3 and extracted with ethyl acetate.

Reference： [1]Lee, Young Hun; Shin, Min Cheol; Yun, Yong Don; Shin, Seo Young; Kim, Jong Min; Seo, Jeong Moo; Kim, Nam-Jung; Ryu, Jong Hoon; Lee, Yong Sup [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 1, p. 231 - 240]
[2]Location in patent: experimental part Shin, Seo Young; Shin, Min Cheol; Shin, Ji-Sun; Lee, Kyung-Tae; Lee, Yong Sup [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 15, p. 4520 - 4523]
[3]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6143779, 2000, A
[4]Kafle, Arjun; Bhattarai, Shrijana; Handy, Scott T. [Tetrahedron, 2020, vol. 76, # 43]

23
[ 6272-26-0 ]
[ 29668-44-8 ]
[ 210360-80-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In methanol	7.1 PRODUCTION EXAMPLE 1 PRODUCTION EXAMPLE 1 After 6-hydroxy-2H-benzofuran-3-one 1 g and 1,4-benzodioxane-6-carboxyaldehyde 1.21 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 55 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60° C. for four hours under reduced pressure to obtain the desired compound 1.17 g. FAB MASS; 297 (M+1) 1 H-NMR (ppm, in DMSO-d6); 4.28 (4H, m), 6.67 (1H, s), 6.70 (1H, dd, J=8.2, 1.8 Hz), 6.77 (1H, d, J=2.1 Hz), 6.64 (1H, d, J=8.2), 7.41 (1H, dd, J=8.5, 2.1 Hz), 7.47 (1H, d, J=2.1 Hz), 7.58 (1H, d, J=8.2 Hz), 11.96 (1H, s)

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6143779, 2000, A

24
[ 6272-26-0 ]
[ 60-29-7 ]
[ 13196-11-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydrogenchloride; In tetrahydrofuran; LiAlH4; water;	Preparation of 6-hydroxybenzofuran In a reactor equipped with a condenser, a thermometer, an addition ampoule, a nitrogen lead in tube and a mechanical stirrer/heating system, there are introduced 600 cm3 of tetrahydrofuran (THF). After degassing with nitrogen, there are added in small amounts 14 g of LiAlH4 over a 30 minute period. At the end of the addition the reaction mixture is heated to 67° C. At this temperature there is added, over a 2 hour period, a solution of 50 g of 6-hydroxy-3-coumaranone dissolved in 1.4 liters of boiling THF. At the end of the addition, the reaction mixture is cooled to 30° C. and then poured into 2 liters of a 2N HCl solution which is vigorously stirred for a period of 30 minutes. After extraction three times with 300 cm3 of ethyl ether and washing the organic phase twice with 200 cm3 of water, the product is dried on magnesium sulfate, filtered and then evaporated to dryness. 50 g of the crude product in oily form are obtained. The crude product is then purified by chromatography on a silica column eluted with dichloromethane. 25 g of the expected product in oily form are obtained. Yield=50percent

Reference： [1]Patent: US5730962,1998,A

25
[ 6272-26-0 ]
[ 77-78-1 ]
[ 15832-09-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 0.833333h;	To a mixture of 6-hydroxybenzofuran-3(2H)-one (60 mg, 0.4 mmol) and K2CO3 (56 mg, 0.4 mmol) in DMF (3 mL), dimethyl sulfate (43L, 0.4 mmol) was added. The mixture was stirred vigorously for 50 min at room temperature. The water (30 mL) was added, and the mixture was extracted with EtOAc (3 × 20 mL). The organic layer was washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel (hexane/EtOAc = 1:6) to give 56 mg (86%) of 6-methoxybenzofuran-3(2H)-one as a light yellow solid, m.p.: 112-114 C. 1H-NMR (DMSO-d6) delta 7.54 (d, J = 6.9 Hz, 1H), 6.82 (d, J = 1.6 Hz, 1H), 6.72 (dd, J = 1.6, 6.9 Hz, 1H), 4.77 (s, 2H), 3.87 (s, 3H). 13C-NMR (DMSO-d6) delta 197.6, 176.3, 168.2, 125.1, 114.5, 112.0, 97.2, 76.0, 56.6. MS (ESI) [M - H]: 149.06.
72.84%	With potassium carbonate; In acetone; at 20℃; for 2h;	To a solution of 1-12 (1.5 g, 10 mmol) in acetone (7 ml) was added K2CO3 (2.073 g, 15 mmol), followed by the addition of dimethyl sulfate (1.387 g, 11 mmol). The mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and diluted with water. The aqueous layer was extracted with dichloromethane (3 * 50 ml), dried with Na2SO3, and evaporated to dryness to yield 2-12 as yellow solid which was used without further purification, 72.84% yield. M.p. 116-118 C (Lit. m.p. 102-103 C); 1H NMR (CDCl3, 500 MHz): delta 7.57 (d, J = 8.6 Hz, H4), 6.65 (dd, J1 = 2 Hz, J2 = 8.6 Hz, H5), 6.55 (d, J = 2 Hz, H7), 4.63 (s, 2H), 3.89 (s, 3H). HRMS (TOF-ES) calcd for C9H9O3+ ([M+1]+): 165.0552, found 165.0535.
68%	With potassium carbonate; In acetone; at 20℃; for 4h;	To a suspension of 6-hydroxybenzofuran-3(2H)-one (1.00?g, 6.66?mmol) in acetone (5?mL) were added K2CO3 (1.38?g, 9.99?mmol) and Me2SO4 (690?muL, 7.28?mmol), and the mixture was stirred at room temperature for 4?h. Solvents were removed under reduced pressure, H2O was added, and the mixture was extracted with CH2Cl2. The combined organic layers were washed with H2O and brine, dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was washed with cold MeOH, filtered and dried to afford 4 (735?mg, 68%) as a pale yellow solid. 1H NMR (CDCl3) delta 7.47 (d, 1H, J?=?8.5?Hz), 6.57 (d, J?=?8.5?Hz), 6.47 (s, 1H), 4.55 (s, 2H), 3.81 (s, 3H). 13C NMR (CDCl3) delta 197.5, 176.5, 168.2, 125.0, 114.3, 111.7, 96.3, 75.5, 55.9.

Reference： [1]Molecules,2019,vol. 24
[2]European Journal of Medicinal Chemistry,2015,vol. 94,p. 195 - 210
[3]European Journal of Medicinal Chemistry,2019,vol. 165,p. 133 - 141
[4]Organic and Biomolecular Chemistry,2008,vol. 6,p. 3486 - 3496

26
[ 6272-26-0 ]
[ 90-02-8 ]
(Z)-6-hydroxy-2-(2-hydroxybenzylidene)benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.5%	With sodium hydroxide; at 20℃; for 3.0h;	In the presence of CH2Cl2 or 5N NaOH, Al2O3 in ethanol (Method A) Or in the presence of SOCl2 in EtOH (Method B)The aryl aldehyde (1) (R = a-f)3-coumaranone (2) or 6-hydroxy-3-coumaranone (3)Was treated at room temperature for 1-6 hours to form a precipitate.Compound (4) - (9) was synthesized according to the aldol condensation reaction (Method A). For example, 3-coumaranone (2.134 g, 10 mmol) and salicylaldehyde (1a, 1.06 mL, 10 mmol) were treated with Al2O3 in the presence of dichloromethane at room temperature for 3 hours. The mixture was then filtered and washed with ethyl acetate. Further purification by column chromatography gave an orange solid.
75%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 3a (2.0 mmol) and benzaldehyde derivative 4 (2.0 mmol) in ethanol was addeddropwise 12N HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into H2O and the resulting precipitate was filtered and dried in vacuo. The crude products were purified by silica gel column chromatography (eluting solvent systems: ethyl acetate/hexanes or methanol/methylene chloride) to give aurones.

Reference： [1]Patent: KR2016/142676,2016,A .Location in patent: Paragraph 0061; 0098; 0099; 0100; 0123; 0124; 0159
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4520 - 4523
[3]European Journal of Medicinal Chemistry,2010,vol. 45,p. 2957 - 2971
[4]ChemBioChem,2014,vol. 15,p. 1325 - 1333

27
[ 6272-26-0 ]
[ 77095-51-3 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1

28
[ 6272-26-0 ]
[ 588703-29-1 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1
[3]Patent: WO2008/141119,2008,A2

29
[ 6272-26-0 ]
[ 6625-96-3 ]
[ 1346151-08-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogenchloride; In ethanol; water; at 70℃; for 3h;	(a) Step 1 A solution of 6-hydroxybenzofuran-3(2H)-one (0.400 g, 2.7 mmol) and <strong>[6625-96-3]5-nitro-1H-indole-3-carboxaldehyde</strong> (0.56 g, 2.9 mmol) in ethanol (5.0 mL) was added with concentrated hydrochloric acid (1.0 mL), and the mixture was stirred at 70C for 3 hours. The reaction mixture was cooled to room temperature, and then the solid was collected by filtration, and washed with methanol to obtain (Z)-6-hydroxy-2-[(5-nitro-1H-indol-3-yl)methylene]benzofuran-3(2H)-one (0.77 g, 90%). 1H NMR (300 MHz, DMSO-d6) delta 6.73 (d, J = 8.8 Hz, 1H), 6.84 (s, 1H), 7.33 (s, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.8 Hz, 1H), 8.11 (dd, J = 2.2 Hz, J = 8.8 Hz, 1H), 8.39 (d, J = 2.2 Hz, 1H), 9.19 (s, 1H), 12.60 (s, 1H)

Reference： [1]Patent: EP2565192,2013,A1 .Location in patent: Paragraph 0199

30
[ 50-00-0 ]
[ 6272-26-0 ]
[ 5235-10-9 ]
[ 147081-29-6 ]
[ 1346151-72-1 ]

Yield	Reaction Conditions	Operation in experiment
6%		(a) Step 1 A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10.0 mmol) in ethanol (10 mL) was added with 1-tert-butoxycarbonyl-3-(S)-methylpiperazine (2.00 g, 10.0 mmol), and 37percent aqueous formaldehyde (0.812 g, 10.0 mmol) at room temperature. The reaction mixture was stirred at 80°C for 8 hours, and then concentrated. The resulting residue was subjected to silica gel column chromatography (hexane/ethyl acetate) to obtain a crude product (0.602 g). A solution of the above crude product in methanol (4 mL) was added with <strong>[5235-10-9]1H-<strong>[5235-10-9]indazole-3-carbaldehyde</strong></strong> (0.162 g, 1.11 mmol), and piperidine (0.00945 g, 0.0111 mmol) at room temperature, and the mixture was stirred at 60°C for 2 hours. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (chloroform/methanol) to obtain tert-butyl (Z)-4-({2-[(1H-indazol-3-yl)methylene]-6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)-3-(S)-methylpiperazine-1-carboxylate (0.329 g, 6percent). 1H NMR (300 MHz, DMSO-d6) delta 1.17 (d, J = 6.6 Hz, 3H), 1.38 (s, 9H), 2.34 (m, 1H), 2.70-2.80 (m, 2H), 3.01-3.23 (m, 2H), 3.40-3.55 (m, 2H), 3.74 (d, J = 13.2 Hz, 1H), 4.19 (d, J = 13.2 Hz, 1H), 6.74 (d, J = 8.8 Hz, 1H), 7.06 (s, 1H), 7.28 (m, 1H), 7.46 (m, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 8.8 Hz, 1H), 8.47 (d, J = 8.1 Hz, 1H), 13.82 (br s, 1H).

Reference： [1]Patent: EP2565192,2013,A1 .Location in patent: Paragraph 0336; 0337

31
[ 50-00-0 ]
[ 55276-43-2 ]
[ 6272-26-0 ]
[ 1346152-68-8 ]

Yield	Reaction Conditions	Operation in experiment
12%	In ethanol; water; at 20℃;	(a) Step 1 A solution of 6-hydroxybenzofuran-3(2H)-one (0.600 g, 4.00 mmol) in ethanol (4 mL) was added with 1-(methylsulfonyl)piperazine (0.657 g, 4.00 mmol), and 37% aqueous formaldehyde (0.325 g, 4.00 mmol) at room temperature. The reaction mixture was stirred overnight at room temperature, and then concentrated. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain 6-hydroxy-7-[4-(methylsulfonyl)piperazin-1-yl]methyl}benzofuran-3(2H)-one (0.169 g, 12%). 1H NMR (300 MHz, DMSO-d6) delta 2.58 (m, 4H), 2.87 (s, 3H), 3.12 (m, 4H), 3.69 (s, 2H), 4.74 (s, 2H), 6.61 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H).

Reference： [1]Patent: EP2565192,2013,A1 .Location in patent: Paragraph 0484

32
[ 6272-26-0 ]
[ 6625-96-3 ]
[ 1346151-09-4 ]

Reference： [1]Patent: EP2565192,2013,A1

33
[ 6272-26-0 ]
[ 5235-10-9 ]
[ 147081-29-6 ]
[ 1346150-21-7 ]

Reference： [1]Patent: EP2565192,2013,A1

34
[ 6272-26-0 ]
[ 1025967-78-5 ]

Reference： [1]Patent: WO2014/18748,2014,A1

35
[ 6272-26-0 ]
[ 13196-11-7 ]
[ 23681-89-2 ]

Reference： [1]Synthetic Communications,2014,vol. 44,p. 1307 - 1313

36
[ 6272-26-0 ]
[ 50551-63-8 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2013,vol. 61,p. 997 - 1001

37
[ 6272-26-0 ]
[ 86-81-7 ]
[ 1613190-06-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium hydroxide; In water; at 20℃; for 4.0h;	General procedure: To a solution of 6-hydroxybenzofuran-3(2H)-one (134mg, 1mmol) in H2O (15mL) at room temperature was added the appropriate aldehyde (1.1mmol) and KOH 1M (2mmol). The mixture was stirred, at room temperature, for 4h. After, some drops of HCl 37% were added to the mixture until the solution reach pH 2. The mixture was extracted with ethyl acetate and combined organic layers were washed with brine, dried with anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product.
90%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
88.24%	With potassium hydroxide; In methanol; water; at 50 - 60℃; for 2.0h;	General procedure: To a solution of 1-12 in methanol (100 mg, 0.67 mmol, 10 ml/mmol) was added the suitably functionalized benzaldehydes (0.67 mmol), followed by a solution of KOH 50% in water (1.5 ml/mmol). The solution is heated at 50-60 C for 2-3 h. The reaction mixture was concentrated in vacuo and diluted with distilled water.The reaction mixture was adjusted to pH 7 with 1 N HCl. The aqueous layer was extracted with ethyl acetate and dried (Na2SO3).The organic phase was evaporated in vacuo to yield crude products which were subjected to column chromatography by using chloroform:methanol (8:2) to yield pure Series 1 aurones.

81%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10 mmol) or 6-hydroxy-7-methylbenzofuran-3(2H)-one (1.64 g,10 mmol) in a mixture of EtOH (10 mL) and DMF (10 mL) was treated with the appropriate aldehyde (10 mmol) and aqueous KOH solution (2.3 mL, 50%), stirred at room temperature for 4-6 h (end of reaction monitored by TLC), stirred vigorously,poured into hot H2O (50 mL), and neutralized with conc. HCl to pH 4-5. The resulting precipitate was filtered off, rinsed with H2O, dried, and recrystallized from DMF-MeOH (1:1).
81%	With potassium hydroxide; In ethanol; N,N-dimethyl-formamide; at 20℃;	General procedure: To a stirred solution of 0.75 g (5 mmol) 6-hydroxybenzofuranone (1) in ethanol (5 mL) and N,N-dimethylformamide (DMF) (5 mL) was added aldehyde (5 mmol) and 1.15 mLof 50% KOH. The mixture was stirred at room temperature for 4-6 h. The mixture was poured into 30 mL of hot water with vigorous stirring and neutralized with concentrated HCl at pH of 1-2. The precipitate was filtered, washed with water, dried and recrystallized from DMF-MeOH.
70%	With sodium hydroxide; In methanol; water; at 30 - 40℃;	General procedure: To a solution of substituted 6-hydroxybenzofuran-3(2H)-one (M3, S3) (3 mmol) and aldehyde derivatives (3 mmol) in methanol; NaOH solution (3 mmol in water) was added, followed by stirring at 30-40 C for 3-4 h. The reaction progress was monitored by TLC examination. After completion of the reaction, the contents were quenched with ice cold water (20 mL) and the resulting precipitate was filtered, dried and subjected to purification by flash chromatography.
	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2)-one (1.50 g, 10 mmol, for the synthesis of compounds 2a-e) or 6-hydroxy-7-methylbenzofuran-3(2)-one (1.64 g, 10 mmol, for the synthesis of compounds 4a-e) and aromatic aldehyde in a 1:1 mixture of DMF-EtOH (50 ml) was treated by adding 50% aqueous solution of KOH (2.3 ml). The mixture was stirred at room temperature for 4-6 h (the completion of reaction was determined by TLC). Then the reaction mixture was poured into vigorously stirred hot H2O (50 ml) and neutralized with concentrated HCl to 4-5. The precipitate that formed was filtered off, washed with H2O, dried, and crystallized from a 1:1 mixture of DMF-MeOH.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 80,p. 523 - 534
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 231 - 240
[3]European Journal of Medicinal Chemistry,2015,vol. 94,p. 195 - 210
[4]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5
[5]Chemical Papers,2018,vol. 72,p. 2443 - 2456
[6]Medicinal Chemistry,2018,vol. 14,p. 44 - 52
[7]Chemistry of Heterocyclic Compounds,2019,vol. 55,p. 212 - 216
Khim. Geterotsikl. Soedin.,2019,vol. 55,p. 212 - 216,5

38
[ 6272-26-0 ]
[ 61343-99-5 ]
[ 1613190-09-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With hydrogenchloride; acetic acid In water at 20℃; for 4h;	4.1.3 General procedure for the synthesis of aurones 5e-g General procedure: To a solution of 6-hydroxybenzofuran-3(2H)-one (0.57mmol) in glacial acetic acid (5.7mL) at room temperature was added the appropriate aldehyde (0.68mmol) and HCl (cat, 3 drops). The reaction mixture was stirred for 4h at room temperature. After, the mixture was dropped in cold water and the precipitate formed was filtered and washed with water.

Reference： [1]Carrasco, Marta P.; Newton, Ana S.; Gonçalves, Lídia; Góis, Ana; Machado, Marta; Gut, Jiri; Nogueira, Fátima; Hänscheid, Thomas; Guedes, Rita C.; Dos Santos, Daniel J.V.A.; Rosenthal, Philip J.; Moreira, Rui [European Journal of Medicinal Chemistry, 2014, vol. 80, p. 523 - 534]

39
[ 6272-26-0 ]
[ 613-45-6 ]
(Z)-2-(2,4-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrogenchloride In ethanol; water at 60 - 70℃;	4.2.11 4.2.7. (Z)-6-Hydroxy-2-(2-methoxybenzylidene)benzofuran-3(2H)-one (9a) General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 °C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
	With potassium hydroxide In ethanol; water; N,N-dimethyl-formamide at 20℃;	Synthesis of 6-hydroxyaurones 2a-e and 4a-e General procedure: A solution of 6-hydroxybenzofuran-3(2)-one (1.50 g, 10 mmol, for the synthesis of compounds 2a-e) or 6-hydroxy-7-methylbenzofuran-3(2)-one (1.64 g, 10 mmol, for the synthesis of compounds 4a-e) and aromatic aldehyde in a 1:1 mixture of DMF-EtOH (50 ml) was treated by adding 50% aqueous solution of KOH (2.3 ml). The mixture was stirred at room temperature for 4-6 h (the completion of reaction was determined by TLC). Then the reaction mixture was poured into vigorously stirred hot H2O (50 ml) and neutralized with concentrated HCl to 4-5. The precipitate that formed was filtered off, washed with H2O, dried, and crystallized from a 1:1 mixture of DMF-MeOH.

Reference： [1]Lee, Young Hun; Shin, Min Cheol; Yun, Yong Don; Shin, Seo Young; Kim, Jong Min; Seo, Jeong Moo; Kim, Nam-Jung; Ryu, Jong Hoon; Lee, Yong Sup [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 1, p. 231 - 240]
[2]Popova, Antonina V.; Bondarenko, Svitlana P.; Vinogradova, Valentina I.; Frasinyuk, Mykhaylo S. [Chemistry of Heterocyclic Compounds, 2019, vol. 55, # 3, p. 212 - 216][Khim. Geterotsikl. Soedin., 2019, vol. 55, # 3, p. 212 - 216,5]

40
[ 6272-26-0 ]
[ 2103-57-3 ]
(2Z)-6-hydroxy-2-(2,3,4-trimethoxybenzylidene)-1-benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride; In ethanol; water; at 60 - 70℃;	General procedure: To a solution of 5 (300 mg, 2.0 mmol) and o-anisaldehyde (403 mg, 3.0 mmol) in EtOH was added dropwise 12 M HCl (3 mL) and heated at 60-70 C until the reaction was finished from TLC monitoring. The mixture was poured into water and the resulting precipitate was filtered and dried in vacuo to give crude 9a (526 mg, 98%). The crude products were used for next reaction without further purification.
78%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10 mmol) or 6-hydroxy-7-methylbenzofuran-3(2H)-one (1.64 g,10 mmol) in a mixture of EtOH (10 mL) and DMF (10 mL) was treated with the appropriate aldehyde (10 mmol) and aqueous KOH solution (2.3 mL, 50%), stirred at room temperature for 4-6 h (end of reaction monitored by TLC), stirred vigorously,poured into hot H2O (50 mL), and neutralized with conc. HCl to pH 4-5. The resulting precipitate was filtered off, rinsed with H2O, dried, and recrystallized from DMF-MeOH (1:1).
78.89%	With potassium hydroxide; In ethanol; water; at 110℃; for 0.2h;Microwave irradiation;	In the following synthesis, the same procedure as Method 3 was employed, but using ethanol in place of methanol. (0463) 1. (Z)-6-hydroxy-2-(2,3,4-trimethoxybenzylidene)benzofuran-3(2H)-one (2912) (0464) Reaction yielded pure product in the amount of 259.0 mg (78.89%) of 2912 as a reddish brown solid (MP = 225-230 C). IR (neat, thin film): 3444.7, 1585.0, 1277,2, 1 140.3, 1 101.5 cm" 1H NMR (Acetone-De, 300 MHz) 8.015 (d, J = 8.58 Hz, 1H), 7.610 (d, J = 8.25 Hz, 1H), 7.036 (s, IH), 6.935 (d, J = 8.91 Hz, IH), 6.810 (d, J = 2.07 Hz, 1H), 6.775 (d, J = 8.22 Hz, 1H) 3.939 is. 3H), 3.916 (s, 3H), 3.819 (s, 3H); i3C NMR (Acetone-D6, 75 MHz) 181.580, 168.062, 165.595, 155.585, 153.654, 147.334, 142.238, 126.607, 125.737, 119.063, 1 14.140, 112.562, 108.174, 104.31 1 , 98,508, 61.279, 60.461 , 55,485.

78%	With potassium hydroxide; In ethanol; N,N-dimethyl-formamide; at 20℃;	General procedure: To a stirred solution of 0.75 g (5 mmol) 6-hydroxybenzofuranone (1) in ethanol (5 mL) and N,N-dimethylformamide (DMF) (5 mL) was added aldehyde (5 mmol) and 1.15 mLof 50% KOH. The mixture was stirred at room temperature for 4-6 h. The mixture was poured into 30 mL of hot water with vigorous stirring and neutralized with concentrated HCl at pH of 1-2. The precipitate was filtered, washed with water, dried and recrystallized from DMF-MeOH.
	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2)-one (1.50 g, 10 mmol, for the synthesis of compounds 2a-e) or 6-hydroxy-7-methylbenzofuran-3(2)-one (1.64 g, 10 mmol, for the synthesis of compounds 4a-e) and aromatic aldehyde in a 1:1 mixture of DMF-EtOH (50 ml) was treated by adding 50% aqueous solution of KOH (2.3 ml). The mixture was stirred at room temperature for 4-6 h (the completion of reaction was determined by TLC). Then the reaction mixture was poured into vigorously stirred hot H2O (50 ml) and neutralized with concentrated HCl to 4-5. The precipitate that formed was filtered off, washed with H2O, dried, and crystallized from a 1:1 mixture of DMF-MeOH.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 231 - 240
[2]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5
[3]Patent: WO2017/180644,2017,A1 .Location in patent: Page/Page column 84
[4]Chemical Papers,2018,vol. 72,p. 2443 - 2456
[5]Chemistry of Heterocyclic Compounds,2019,vol. 55,p. 212 - 216
Khim. Geterotsikl. Soedin.,2019,vol. 55,p. 212 - 216,5

41
[ 6272-26-0 ]
[ 15182-92-0 ]
(Z)-2-(4-(2-(dimethylamino)ethoxy)benzylidene)-6-hydroxybenzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In methanol; water; at 50 - 60℃;	General procedure: To a solution of 1-12 in methanol (100 mg, 0.67 mmol, 10 ml/mmol) was added the suitably functionalized benzaldehydes (0.67 mmol), followed by a solution of KOH 50% in water (1.5 ml/mmol). The solution is heated at 50-60 C for 2-3 h. The reaction mixture was concentrated in vacuo and diluted with distilled water.The reaction mixture was adjusted to pH 7 with 1 N HCl. The aqueous layer was extracted with ethyl acetate and dried (Na2SO3).The organic phase was evaporated in vacuo to yield crude products which were subjected to column chromatography by using chloroform:methanol (8:2) to yield pure Series 1 aurones.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 94,p. 195 - 210

42
[ 6272-26-0 ]
[ 15182-92-0 ]
(Z)-2-(4-(2-(dimethylamino)ethoxy)benzylidene)-3-oxo-2,3-dihydrobenzofuran-6-yldiethylcarbamate [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 94,p. 195 - 210

43
[ 6272-26-0 ]
[ 26934-35-0 ]
(Z)-2-(4-(3-(dimethylamino)propoxy)benzylidene)-6-hydroxybenzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide In methanol; water at 50 - 60℃;	5.2.4. Condensation of 1-12 with functionalized benzaldehydes General procedure: To a solution of 1-12 in methanol (100 mg, 0.67 mmol, 10 ml/mmol) was added the suitably functionalized benzaldehydes (0.67 mmol), followed by a solution of KOH 50% in water (1.5 ml/mmol). The solution is heated at 50-60 C for 2-3 h. The reaction mixture was concentrated in vacuo and diluted with distilled water.The reaction mixture was adjusted to pH 7 with 1 N HCl. The aqueous layer was extracted with ethyl acetate and dried (Na2SO3).The organic phase was evaporated in vacuo to yield crude products which were subjected to column chromatography by using chloroform:methanol (8:2) to yield pure Series 1 aurones.

Reference： [1]Liew, Kok-Fui; Chan, Kit-Lam; Lee, Chong-Yew [European Journal of Medicinal Chemistry, 2015, vol. 94, p. 195 - 210]

44
[ 6272-26-0 ]
[ 56317-21-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: 1H-imidazole / tetrahydrofuran / 4 h / 0 - 20 °C 2.1: sodium tetrahydroborate / methanol / 4 h / 20 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C 3.2: -78 - 20 °C 3.3: 20 °C / pH 5 4.1: potassium carbonate; palladium diacetate; tricyclohexylphosphine / water; 1,2-dimethoxyethane / 2 h / 80 °C / Inert atmosphere 5.1: 1H-imidazole / tetrahydrofuran / 2 h / 20 °C 6.1: n-butyllithium; diphenylphosphane / tetrahydrofuran; hexane / 36 h / Inert atmosphere; Reflux

Reference： [1]Wu, Deyan; Mei, Hanbing; Tan, Ping; Lu, Weiqiang; Zhu, Jin; Wang, Wei; Huang, Jin; Li, Jian [Tetrahedron Letters, 2015, vol. 56, # 29, p. 4383 - 4387]

45
[ 6272-26-0 ]
[ 120-57-0 ]
[ 32396-84-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium hydroxide In ethanol; N,N-dimethyl-formamide at 20℃;	Synthesis of 6-hydroxyaurones 1a-d (Generalmethod). General procedure: The appropriate aldehyde (10 mmol) and 50%aqueous KOH solution (2.3 ml) were added to a solution of6-hydroxybenzofuran-3(2)-one (1.50 g, 10 mmol) in amixture of EtOH (10 ml) and DMF (10 ml). The mixturewas stirred at room temperature for 4-6 h (the completionof the reaction was observed by TLC). The reaction mixturewas poured into hot water (50 ml) with vigorous stirringand neutralized with concd. HCl to 4-5. The precipitatethat formed was filtered off, washed with water, dried, andrecrystallized from 1:1 DMF- mixture. The NMRdata for compounds 1- matched the literature.14 2-[(1,3-Benzodioxol-5-yl)methylidene]-6-hydroxy-1-benzofuran-3(2H)-one (1d). Yield 91%, yellow crystals, mp321-323°C. IR spectrum, ν, cm-1: 3046, 2590, 1668, 1558,1446, 1404, 1330, 1102. 1H NMR spectrum (400 MHz,DMSO-d6), δ, ppm (J, Hz): 6.11 (2H, s, OCH2O); 6.71(1H, dd, 3J = 8.5, 4J = 2.0, -5); 6.74 (1H, s, =CH-Ar); 6.81(1H, d, 4J = 2.0, -7); 7.04 (1H, d, 3J = 8.1, -7'); 7.47 (1H,dd, 3J = 8.2, 4J = 1.6, -6'); 7.55 (1H, d, 4J = 1.6, -4');7.60 (1H, d, 3J = 8.4, -4). 13C NMR spectrum (100 MHz,DMSO-d6), δ, ppm: 98.6; 101.6; 108.8; 110.0; 110.6;112.8; 112.9; 125.7; 126.1; 126.8; 146.2; 147.7; 148.5;166.4; 167.5; 181.0. Mass spectrum, m/z (Irel, %): 283.2[+H]+ (100). Found, %: C 68.12; H 3.62. C16H10O5.Calculated, %: C 68.09; H 3.57.

Reference： [1]Popova, Antonina V.; Bondarenko, Svitlana P.; Frasinyuk, Mykhaylo S. [Chemistry of Heterocyclic Compounds, 2016, vol. 52, # 8, p. 592 - 600][Khim. Geterotsikl. Soedin., 2016, vol. 52, # 8, p. 592 - 600,9]

46
[ 6272-26-0 ]
halomethane [ No CAS ]
[ 15832-09-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	General procedure: To a solution of 1.5 g (10 mmol) 6-hydroxybenzofuranone (2a)in 20 mL DMF was added K2CO3 (4.14 g, 30 mmol) and correspondingalkyl halide (11 mmol). The reaction mixture was stirred at r.t.for 4-6 h, filtered, and solvent evaporated under vacuum. The residuewas dissolved in acidified water and extracted with CH2Cl2(30 mL). The organic fraction was separated, dried with anhydrousNa2SO4, and solvent was evaporated under vacuum. Re-crystallizationof the residue from an appropriate solvent gave benzofuranones2b-2g as a yellow solid.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3606 - 3613

47
[ 6272-26-0 ]
[ 71653-64-0 ]
(1R,5S)-3-({(2Z)-6-hydroxy-2-[2-(difluoromethoxy)benzylidene]-3-oxo-2,3-dihydro-1-benzofuran-7-yl}methyl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one [ No CAS ]

Reference： [1]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5

48
[ 6272-26-0 ]
[ 71653-64-0 ]
(2Z)-6-hydroxy-2-[2-(difluoromethoxy)benzylidene]-1-benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With potassium hydroxide; In ethanol; water; N,N-dimethyl-formamide; at 20℃;	General procedure: A solution of 6-hydroxybenzofuran-3(2H)-one (1.50 g, 10 mmol) or 6-hydroxy-7-methylbenzofuran-3(2H)-one (1.64 g,10 mmol) in a mixture of EtOH (10 mL) and DMF (10 mL) was treated with the appropriate aldehyde (10 mmol) and aqueous KOH solution (2.3 mL, 50%), stirred at room temperature for 4-6 h (end of reaction monitored by TLC), stirred vigorously,poured into hot H2O (50 mL), and neutralized with conc. HCl to pH 4-5. The resulting precipitate was filtered off, rinsed with H2O, dried, and recrystallized from DMF-MeOH (1:1).

Reference： [1]Chemistry of Natural Compounds,2017,vol. 53,p. 708 - 713
Khim. Prir. Soedin.,2017,p. 603 - 607,5

49
[ 6272-26-0 ]
[ 1083168-69-7 ]

Reference： [1]Patent: WO2008/141119,2008,A2

50
[ 6272-26-0 ]
[ 2144-08-3 ]
(2E)-6-hydroxy-2-(2,3,4-trihydroxybenzylidene)benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With piperazine In ethanol at 80℃;	Chemistry General procedure: Solution of 6-hydroxy-3-benzofuranones (1 mmol), and appropriate aryl aldehyde (1 mmol) in ethanol (5 ml) were added to piperazine (0.5 mmol) as the basic catalyst. The reaction mixture was heated in 80 °C for 12-24 h, then was allowed to stand at room temperature for the next 24 h. The precipitate was filtered, dried, and crystallized from acetic acid to afford pure 6-hydroxy-2-benzylidene-3-benzofuranones. Structural assignments of the products are based on their IR, 1H-NMR, MS and melting point [20, 21].

Reference： [1]Abbasbeigi, Sirvan; Adibi, Hadi; Moradi, Sajad; Ghadami, Seyyed Abolghasem; Khodarahmi, Reza [Journal of the Iranian Chemical Society, 2019, vol. 16, # 6, p. 1225 - 1237]

51
[ 6272-26-0 ]
[ 2014-83-7 ]
6-((2,6-dichlorobenzyl)oxy)benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium carbonate; In N,N-dimethyl-formamide; at 25℃; for 8h;	To a solution of 1.5 g (10 mmol) of 6-hydroxybenzofuran-3(2H)-one (1) in 30 mL of N,N-dimethylformamide was added 4.14 g (30 mmol, 3 eq) of anhydrous potassium carbonate followed by 2.35 g (12 mmol, 1.2 eq) of 2,6-dichlorobenzylchloride (Acros Organics). The mixture was stirred at 25oC for 8 h and diluted with 200 mL of water. The precipitate was collected, washed with water, dried and purified by column chromatography using 1:100 dichloromethane-methanol to afford 1.79 g (58%) of 6-((2,6- dichlorobenzyl)oxy)benzofuran-3(2H)-one as pale yellow crystals: mp 153-155 oC. 1H NMR (400 MHz, CDCl3) delta 4.64 (s, 2H), 5.34 (s, 2H), 6.67-6.77 (m, 2H), 7.29 (d, J = 7.2 Hz, 1H), 7.33-7.42 (m, 2H), 7.58 (d, J = 9 Hz, 1H); 13C NMR (100 MHz, CDCl3) delta 65.57, 75.56, 97.32, 111.98, 114.76, 125.15, 128.56, 130.9, 130.96, 136.97, 167.18, 176.32, 197.49 ppm; MS (ACPI) m/z 309.2 (MH+, 100).

Reference： [1]Patent: WO2019/144009,2019,A1 .Location in patent: Paragraph 00143-00144

52
[ 4649-09-6 ]
[ 6272-26-0 ]
(Z)-2-((1H-pyrrolo[2,3-b]pyridin-3-yl)methylene)-6-hydroxybenzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrogenchloride; In methanol; water; at 60 - 80℃; for 6h;	General procedure: To a solution of (7) 1-(<strong>[4649-09-6]1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde</strong> (0.300g, 2.053mmol) in 32% aqueous HCl/methanol (1.5:1 v/v) (4.5ml/3 ml) was added a selected bicyclic scaffold (tetralone, indanone, 3-coumaranone, 4-chromanone and thiochroman-4-one) (2.053mmol) and the reaction was refluxed for at least 6h at 60-80C. The progress of the reaction was monitored by silica gel TLC with ethyl acetate as mobile phase. When the reaction reached completion, the target products were isolated by precipitation with ice-cold water, after which they were purified by recrystallisation with ethanol.

Reference： [1]Bioorganic and medicinal chemistry,2020

53
[ 6272-26-0 ]
[ 19463-48-0 ]
(2Z)-2-[(3-chloro-4-hydroxy-5-methoxyphenyl)methylene]-6-hydroxybenzofuran-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With hydrogenchloride In water; isopropyl alcohol at 80℃; for 16h;	4.1.4. General procedure of synthesis of aurones 9-15 General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.

Reference： [1]Bdzhola, V. G.; Bilokin, Y. V.; Borysenko, I. P.; Lukashov, S. S.; Protopopov, M. V.; Prykhod'ko, A. O.; Starosyla, S. A.; Vdovin, V. S.; Yarmoluk, S. M. [Bioorganic Chemistry, 2020, vol. 102]

54
[ 6272-26-0 ]
[ 454-89-7 ]
6-hydroxy-3'-trifluoromethylaurone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97.4%	With potassium hydroxide In water at 25℃;	Compounds 25-36, 43-48 were synthesized by using base catalyzed aldol condensation reaction (Method C) General procedure: To a reaction mixture of 6-hydroxy benzofuran-3(2H)-one (1.0 equiv.) and aryl aldehydes (1.2 equiv.) in 50 % aqueous potassium hydroxide solution (3.0 mL) was added dropwise and stirred at room temperature for 2-3 h. Upon completion of reaction after monitoring by TLC, the reaction was neutralized with 2N HCl solution to pH 1-2. The resulted precipitate was filtered, washed with distilled water and hexane to obtain pure compound.

Reference： [1]Shrestha, Aarajana; Shrestha, Ritina; Lee, Sumin; Park, Pil-Hoon; Lee, Eung-Seok [Bulletin of the Korean Chemical Society, 2021, vol. 42, # 3, p. 372 - 375]

55
[ 6272-26-0 ]
[ 94651-33-9 ]
6-hydroxy-2-(2-(trifluoromethoxy)benzylidene)benzofuran-3-(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.6%	With potassium hydroxide In water at 25℃;	Compounds 25-36, 43-48 were synthesized by using base catalyzed aldol condensation reaction (Method C) General procedure: To a reaction mixture of 6-hydroxy benzofuran-3(2H)-one (1.0 equiv.) and aryl aldehydes (1.2 equiv.) in 50 % aqueous potassium hydroxide solution (3.0 mL) was added dropwise and stirred at room temperature for 2-3 h. Upon completion of reaction after monitoring by TLC, the reaction was neutralized with 2N HCl solution to pH 1-2. The resulted precipitate was filtered, washed with distilled water and hexane to obtain pure compound.

Reference： [1]Shrestha, Aarajana; Shrestha, Ritina; Lee, Sumin; Park, Pil-Hoon; Lee, Eung-Seok [Bulletin of the Korean Chemical Society, 2021, vol. 42, # 3, p. 372 - 375]

56
[ 6272-26-0 ]
[ 52771-21-8 ]
6-hydroxy-2-(3-(trifluoromethoxy)benzylidene)benzofuran-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35.9%	With potassium hydroxide In water at 25℃;	Compounds 25-36, 43-48 were synthesized by using base catalyzed aldol condensation reaction (Method C) General procedure: To a reaction mixture of 6-hydroxy benzofuran-3(2H)-one (1.0 equiv.) and aryl aldehydes (1.2 equiv.) in 50 % aqueous potassium hydroxide solution (3.0 mL) was added dropwise and stirred at room temperature for 2-3 h. Upon completion of reaction after monitoring by TLC, the reaction was neutralized with 2N HCl solution to pH 1-2. The resulted precipitate was filtered, washed with distilled water and hexane to obtain pure compound.

Reference： [1]Shrestha, Aarajana; Shrestha, Ritina; Lee, Sumin; Park, Pil-Hoon; Lee, Eung-Seok [Bulletin of the Korean Chemical Society, 2021, vol. 42, # 3, p. 372 - 375]

57
[ 6272-26-0 ]
[ 4021-50-5 ]
C₁₆H₉F₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide In ethanol; water at 20℃;	4.1.2. General synthetic procedure for targets 1-16 General procedure: In a dry round-bottomed flask, 6-hydroxy-2,3-dihydrobenzo[b]furan-3-one (E, 1.0 equiv.) and substituted benzaldehyde (1.5equiv.), potassium hydroxide (1.0 equiv.) solved in ethanol, then themixture was reacted overnight at room temperature. After the reactionwas completed (monitored by TLC), con. hydrochloric acidwas added slowly at 0 °C. The solid was precipitated from themixture, the corresponding product F was obtained by filtration.

Reference： [1]Liu, Kai; Zhao, Xing; Qi, Xue; Hou, Dong-Liang; Li, Hao-Bin; Gu, Yu-Hao; Xu, Qing-Long [European Journal of Medicinal Chemistry, 2021, vol. 218]

58
[ 6272-26-0 ]
[ 10601-19-1 ]
[ 1200534-45-7 ]

Yield	Reaction Conditions	Operation in experiment
42%	With potassium hydroxide In methanol; lithium hydroxide monohydrate at 25℃;	General procedure for the synthesis of compounds 1-18 (method A). General procedure: To a suspension of 1 mmol of 6-hydroxybenzofuran-3(2H)-one in 5 mL of a 1 : 1 mixture of water and methanol was added 1 mL of 50% aqueous KOH. To this clear solution, obtained after stirring for 10 min, was added 1.2 mmol of the appropriate carboxaldehyde. The mixture was stirred for 6-8 h at 25°C then diluted with 20 mL of hot water and acidified with glacial acetic acid to pH 5. The resulting precipitate was collected by filtration, washed with water, dried and recrystallized from methanol to give the corresponding target compounds.

Reference： [1]Li, Yi; Zhao, Haiqing; Niu, Chao; Aisa, Haji Akber; Hou, Xueling [Russian Journal of General Chemistry, 2022, vol. 92, # 8, p. 1562 - 1573][Zh. Obshch. Khim., 2022, vol. 92, # 8, p. 1562 - 1573]

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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. 6272-26-0 ]

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[ 6272-26-0 ] Synthesis Path-Upstream 1~8

[ 6272-26-0 ] Synthesis Path-Downstream 1~58

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Alcohols

Ketones

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Benzofurans

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[ 6272-26-0 ]

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[ 6272-26-0 ]