[ CAS No. 118-61-6 ] {[proInfo.proName]}

Name: 118-61-6|Ethyl 2-hydroxybenzoate|98%
Brand: Ambeed
SKU: A229111
Price: 7.0 USD
Availability: InStock
Rating: 91 (27 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 118-61-6

Structure of 118-61-6 * Storage: {[proInfo.prStorage]}

Please Login or Create an Account to: See VIP prices and availability

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

For Research Only 120K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 118-61-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 118-61-6 ]

SDS Specification

Alternatived Products of [ 118-61-6 ]

Product Details of [ 118-61-6 ]

CAS No. :	118-61-6	MDL No. :	MFCD00002215
Formula :	C₉H₁₀O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GYCKQBWUSACYIF-UHFFFAOYSA-N
M.W :	166.17	Pubchem ID :	8365
Synonyms :

Calculated chemistry of [ 118-61-6 ] Expand+

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	44.55
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) :	-5.22 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.05
Log Po/w (XLOGP3) :	2.95
Log Po/w (WLOGP) :	1.57
Log Po/w (MLOGP) :	1.64
Log Po/w (SILICOS-IT) :	1.55
Consensus Log Po/w :	1.95

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.9
Solubility :	0.209 mg/ml ; 0.00126 mol/l
Class :	Soluble
Log S (Ali) :	-3.59
Solubility :	0.0428 mg/ml ; 0.000257 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.29
Solubility :	0.842 mg/ml ; 0.00507 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.35

Safety of [ 118-61-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P273-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H412	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 118-61-6 ]

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

Upstream synthesis route of [ 118-61-6 ]
Downstream synthetic route of [ 118-61-6 ]

[ 118-61-6 ] Synthesis Path-Upstream 1~5

1
[ 5470-11-1 ]
[ 118-61-6 ]
[ 89-73-6 ]

Reference： [1] Patent: EP1308439, 2003, A1,

2
[ 118-61-6 ]
[ 89-73-6 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1970, p. 2573 - 2580

3
[ 118-61-6 ]
[ 13099-95-1 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 21, p. 5584 - 5587

4
[ 118-61-6 ]
[ 15125-84-5 ]

Reference： [1] European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3234 - 3239
[2] Organic and Biomolecular Chemistry, 2012, vol. 10, # 27, p. 5230 - 5237

5
[ 118-61-6 ]
[ 2100-31-4 ]

Reference： [1] Journal of the Chemical Society, 1944, p. 19

[ 118-61-6 ] Synthesis Path-Downstream 1~69

1
[ 106-95-6 ]
[ 118-61-6 ]
[ 61493-61-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium carbonate In acetone for 18h; Reflux;	4 Ethyl 2-(allyloxy)benzoate 20³⁸ To a solution of ethyl 2-hydroxybenzoate (1.3 g, 7.8 mmol) in acetone (50 mL) and K2CO3 (3.33 g, 24.1 mmol) was added allyl bromide (2.1 mL, 2.9 g, 24.0 mmol). The reaction mixture was stirred under reflux for 18 h after which H2O (50 mL) was added and the crude product extracted with EtOAc (4 * 100 mL). The residue produced was purified by column chromatography using EtOAc:hexane (5:95) as eluent to afford the product 20 as a colourless oil (1.54 g, 96% yield). 1H NMR (300 MHz, CDCl3): δ(ppm) = 1.38 (t, 3H, J 7.1 Hz, CH3), 4.36 (q, 2H, J 7.1 Hz, OCH2CH3), 4.61 (s, 2H, OCH2CH), 5.29 (d, 1H, J 10.5 Hz, cis OCH2CH=CH2), 5.51 (dd, 1H, J 17.4, 1.5 Hz, trans OCH2CH=CH2), 6.01-6.07 (m, 1H, OCH2CH=CH2), 6.93-7.00 (m, 2H, 2 * ArH), 7.43 (dd, 1H, J 1.0, 7.5 Hz, ArH), 7.79 (dd, 1H, J 1.5, 7.5, Hz, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm) = 14.2 (CH3), 60.6 CH2), 69.3 (CH2), 113.5 (CH), 117.2 (CH2), 120.2 (CH), 120.9 (C), 131.4 (CH), 132.6 (CH), 133.0 (CH), 157.8 (C), 166.2 (C=O); HRMS; M+, calcd for C12H14O3 206.0943, found 206.0942.
88%	Stage #1: 2-hydroxy-benzoic acid ethyl ester With caesium carbonate In N,N-dimethyl-formamide Stage #2: allyl bromide In N,N-dimethyl-formamide at 60℃; for 4h;
84%	With potassium carbonate In N,N-dimethyl-formamide for 21h; Ambient temperature;

	With potassium carbonate; acetone
4.9 g	With potassium carbonate; sodium iodide In acetone for 15h; Reflux;
	With potassium carbonate In butanone for 48h; Heating / reflux;	2 Example 2: Preparation of 2-Allyloxy-benzoic acid (Compound 1): Under N2, the mixture of ethyl salicylate (16.62 g, 100 mmol), allyl bromide (18.15 g, 12.7 ml, 150 mmol) and potassium carbonate (17.97 g5 130 mmol) in dry 2-butanone (400 ml) was heated to reflux for 48h. After the reaction mixture cooled down to 250C, the suspended inorganic salt was removed by filtration. The concentration of the resulting solution by rotary evaporation yielded pale yellowish syrup, which was then mixed with 2N NaOH (80 ml, 160 mmol) and EtOH (150 ml). After this mixture was stirred for 2h at 5O0C, ethanol was removed at reduced pressure. The aqueous solution was acidified by 6N HCl to pH 2 at 50C to generate white precipitate, which was then collected by filtration. The recrystallization of this crude product from hexane/ether yielded pure 2- Allyloxy-benzoic acid as colorless crystal (14.87g, 83.5%). Microanalysis CaIc. for Ci0H10O3 (178.19): C 67.41, H 5.66; found: C 67.35, H 5.39. 1H-NMR (400 MHz, d6-DMSO): 12.51 (s, -CO2H); 7.55 (m, 1 arom. η); 7.38 (m, 1 arom. η); 7.01 (m, 1 arom. η); 6.90 (m, 1 arom. η); 5.93 (m, -CH=CH2); 5.40, 5.15 (2 d-like, 4.57 (d-Iike, CH2-CH=CH2). 13C-NMR (IOO MHz, d6-DMSO): 167.35 (-C=O); 156.88; 133.36; 132.81 ; 130.62; 121.68; 120.16; 116.91 ; 113.64; 68.52.
	With potassium carbonate In acetone at 25℃;
	With potassium carbonate

Reference： [1]Aderibigbe, Blessing A.; Green, Ivan R.; Mabank, Tanya; Janse van Rensburg, Mari; Morgans, Garreth L.; Fernandes, Manuel A.; Michael, Joseph P.; van Otterlo, Willem A.L. [Tetrahedron, 2017, vol. 73, # 31, p. 4671 - 4683]
[2]Brady, Ryan M.; Khakham, Yelena; Lessene, Guillaume; Baell, Jonathan B. [Organic and Biomolecular Chemistry, 2011, vol. 9, # 3, p. 656 - 658]
[3]Black, Michael; Cadogan, J. I. G.; McNab, Hamish [Journal of the Chemical Society. Perkin transactions I, 1994, # 2, p. 155 - 160]
[4]Lespagnol; Bar [Bulletin de la Societe Chimique de France, 1938, vol. <5> 5, p. 1360,1362]
[5]Location in patent: experimental part Majumdar, Krishna C.; Chattopadhyay, Buddhadeb; Ansary, Inul [Canadian Journal of Chemistry, 2009, vol. 87, # 3, p. 472 - 477]
[6]Current Patent Assignee: NOVO NORDISK A/S - WO2008/116141, 2008, A1 Location in patent: Page/Page column 31
[7]Begam, Hasina Mamataj; Jana, Ranjan; Manna, Kartic; Samanta, Krishanu [Organic Letters, 2020, vol. 22, # 19, p. 7443 - 7449]
[8]Manna, Kartic; Begam, Hasina Mamataj; Jana, Ranjan [Synthesis, 2022, vol. 55, # 10, p. 1543 - 1552]

2
[ 64-17-5 ]
[ 69-72-7 ]
[ 118-61-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sulfuric acid for 4h; Reflux;
97.25%	With sulfuric acid In water monomer for 4h; Reflux;	II.B.7.A To a solution of 2-hydroxybenzoic acid (63) (5.0 g, 36.2 mmol) in anhydrous EtOH (150 ml) was added 98% H2SO4 (4 ml). The mixture was refluxed for 4 h and concentrated. The residue was extracted with CH2Cl2 dried over MgSO4 and evaporated. The crude was purified by distillation to give 68 as colorless liquid. (5.85 g, 35.21 mmol). Yield: 97.25%; MS (EI, 70 eV): m/z 166.2 (M+); 1H-NMR (CDCl3, 200 MHz): δ 1.39 (t, J=7.2 Hz, 3H), 4.37 (q, J=7.2, 7.0 Hz, 2H), 6.81 (t, J=6.6 Hz, 1H), 6.89 (d, J=8.0 Hz, 1H), 7.42 (t, J=7.2 Hz, 1H), 7.82 (dd, J1=8.0, 1.8 Hz, 1H), 10.83 (s, 1H); 13C-NMR (CDCl3, 50 MHz) δ: 170.20, 161.64, 135.56, 129.89, 119.06, 117.53, 61.40, 14.18; Anal. Calcd for C9H10O3: C, 65.05; H, 6.07.
96%	With alumina methanesulfonic acid at 120℃; for 0.333333h; Microwave irradiation;	Representative Procedure for Preparation of Aromatic and Aliphatic Esters (Table 1) General procedure: In a typical reaction, AMA 2:3 (332 g, 0.6 mol), the corresponding carboxylicacid (1 mol), and alcohol (1.5-2 mol) were mixed in the provided reaction glass tubeequipped with a screw cap and magnetic agitation until a wet mixture was achieved.The reaction mixture was irradiated with microwaves (Anton Parr Monowave 300reactor) at 80 C for 8 min or 120 C for 20 min. On cooling, the mixture was diluted with dichloromethane (41 mL), filtered under gravity, and washed with dichloromethane;then the filtrate was washed with Na2CO3 (ss) and water. The organic layerwas dried over Na2SO4, filtered, and concentrated under reduced pressure to give theester.

91%	With nano-SiO₂-supported Preyssler heteropolyacid In dichloroethane at 80℃; for 0.05h; Microwave irradiation;
84%	With hydrogenchloride for 0.0833333h; Irradiation;
84%	With sulfuric acid for 24h; Reflux; Molecular sieve;
71%	Stage #1: ethanol; 2-hydroxy-1-benzoic acid With dmap In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃;	Synthesis of ethyl 2-(p-tolyl)acetate (1a), ethyl 2-(2-hydroxyphenyl)acetate (1b), ethyl 2-(naphthalen-1-yl)acetate (1c) General procedure: 2-(p-tolyl)acetic acid (150.18 mg, 1 mmol) and DMAP (183.20 mg, 1.5 mmol) were added to a two-necked flask, and followed by the addition of 1 mL ethanol and 10 mL anhydrous dichloromethane (DCM). The mixture was stirred for 1 h at room temperature under N2, then EDC (95.8 mg, 0.5 mmol, dissolved in DCM) was added dropwise. After an overnight stir at room temperature under N2, deionized water was added. The reaction solution was extracted three times with DCM, which was later concentrated under reduced pressure. 133.5 mg of white solid (1a) was collected by silica gel column chromatography using a mixture of EtOAc and petroleum ether (V/V, 1:1) Yield 75 % ,1H NMR (400 MHz, CDCl3) δ(ppm) 7.92-7.94 (d, J=8.0 Hz, 2H); 7.21-7.23 (d, J=8.0 Hz, 2H); 4.33-4.38 (q, J=14.0 Hz, 2H); 2.40 (s,3H); 1.36-1.39 (t, J=7.2,3H). 13C NMR (101 MHz, CDCl3) δ=166.78, 143.48, 129.62, 129.08, 128.74, 60.82, 26.89, 21.70, 14.41. HR-MS (TOF): m/z Calcd. For C10H13O2 (M + H+): 106.0910; Found: 106.0910.
70%	With sulfuric acid for 48h; Reflux;	10.1 H2SO4 (1.5 mL, 28.14 mmol) was added to a solution of salicylic acid (1.50 g, 10.860 mmol) in EtOH (50 mL). The reaction mixture was refluxed for 2 days, allowed to reach r.t., and it was diluted with CH2Cl2 (200 mL). The organic layer was washed with Na2CO3 (1 M aqueous solution, 200 mL). It was dried over Na2SO4 (anhydrous), filtered and concentrated to furnish 1.26 g of ethyl 2-hydroxybenzoate (yellow-coloured oil, yield: 70%).1H NMR (CDCl3, 250 MHz) δ ppm: 10.89 (s, 1H), 7.84 (dd, J1=8.5 Hz, J2=8.0 Hz, 1H), 7.43 (t, J=8.5 Hz, 1H), 6.96 (d, J=8.5 Hz, 1H), 6.86 (t, J=7.3 Hz, 1H), 4.40 (c, J=7.1 Hz, 2H), 1.40 (t, J=7.1 Hz, 3H).
70%	With sulfuric acid for 48h; Reflux;	B-10.1 Step 1 : Ethyl 2-hydroxybenzoate Step 1 : Ethyl 2-hydroxybenzoate H2SO4 (1.5 mL, 28. 14 mmol) was added to a solution of salicylic acid (1.50 g, 10.860 mmol) in EtOH (50 mL). The reaction mixture was refluxed for 2 days, allowed to reach r.t., and it was diluted with CH2CI2 (200 mL). The organic layer was washed with Na2C03 (1 M aqueous solution, 200 mL). It was dried over Na2S04 (anhydrous), filtered and concentrated to furnish 1 .26 g of ethyl 2-hydroxybenzoate (yellow-coloured oil, yield: 70%). NMR (CDCI3, 250 MHz) δ ppm: 10.89 (s, lH), 7.84 (dd, J, = 8.5 Hz, J2 = 8.0 Hz, 1H), 7.43 (t, J= 8.5 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 6.86 (t, J= 7.3 Hz, 1H), 4.40 (c, J= 7.1 Hz, 2H), 1.40 (t, J= 7.1 Hz, 3H).
66.5%	With sulfuric acid Reflux;
65%	With thionyl chloride at 0 - 80℃; for 12h;	Preparation of ethyl 2-hydroxybenzoate Thionyl chloride (20 ml, 0.275 mmol) was added dropwise to a stirred solution of salicylic acid(10 g, 0.0724 mmol) in ethanol (50 ml) at 0°C and themixture was stirred for 12h at 80°C. After completionof starting material (TlC monitoring), the reactionmixture was concentrated to remove the unreactedthionyl chloride and ethanol under reduced pressure.The residue was diluted with water and extractedwith MTBE solvent . The organic layer was washedwith an aqueous solution of NaHCO3 (10%), driedwith sodium sulfate and concentrated under reducedpressure to obtain the pure product as a brown colorliquid (Yield: 65%). 1H-NMR(400 MHz, DMSO-d6):d = 10.58 (s, 1H, OH), 7.79 (d, J = 7.6 Hz, 1H),7.51 (t, J = 8.0 Hz, 1H), 6.93-7.00 (m, 2H), 4.37(q, J = 6.8 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H) ppm; IR:3189 (O-H, phenol), 2988, 1675, 1614, 1480, 1300,1249, 1216, 1091, 808, 756, 705 cm-1.
62.5%	With mineral acid at 100℃; for 12h;	Confirmation of bioethanol General procedure: The bioethanol is a volatile liquid and it is quite difficult to characterize in its volatile liquidform at laboratory scale, therefore, the bioethanol obtained from banana peels was directlyconverted into its UV active and non-volatile derivative namely ethyl benzoate whereas thebioethanol from radish leaves converted into ethyl salicylate. For this purpose, fermentedmixture (440 mL) containing bioethanol, benzoic acid (1 g) or salicylic acid (1 g) and conc. HCl(0.2 mL for each) were taken in an Erlenmeyer flask and fitted with the water condenser usingchiller (Buchi, Germany) separately. The reaction assemblies were placed in the water bath andrefluxed at 100 °C for 12 hours. The product mixtures were allowed to cool down at roomtemperature. The desired products ethyl benzoate and ethyl salicylate were extracted from thecrude mixture by using n-hexane:ethyl acetate (100 mL:100 mL). The content of the flask wasthoroughly mixed and then allowed to settle down for the separation of the layers. The waterlayer (lower) and organic solvent layer (upper) were separated by separating funnel, and processof extraction was repeated three times. The water layer was discarded and the organic solventlayers were concentrated using rotary evaporator. The concentrated ethyl benzoate (59.3%) and ethyl salicylate (62.5%) were examined by thin layer chromatography (TLC) using standardethyl benzoate and ethyl salicylate prepared by the same procedure using known starting materials. n-Hexane was used as the solvent system for TLC. The spots were identified by UV lamp at 254 nm. The spots of the sample ethyl benzoate and standard were appeared at the same Rf value (0.76).
55%	With sulfuric acid for 15h; Reflux;
48%	With sulfuric acid at 0 - 85℃; for 16h;	1.1 Step 1:2-hydroxy ethyl benzoate synthesis of The 2-hydroxy-benzoic acid (10g, 72mmol, 1eq.) dissolved in EtOH (31.5 ml), at 0 °C lower dropwise adding concentrated sulfuric acid (0.5 ml, 9 . 39mmol), the reaction solution is heated to 85 °C reaction 16h. After the reaction end, concentrated reaction solution, for residue 20 ml water dilution, dichloromethane is used for (20 ml x 2) extraction, drying with anhydrous sodium sulfate, concentrated under reduced pressure to obtain colorless oily target compound (5.77g, 48%).
46%	With thionyl chloride for 2h; Heating;
	With hydrogenchloride
	With sulfuric acid
	With anhydrous copper sulphate; sulfuric acid; copper(II) sulphate
	With potassium pyrosulfate; sulfuric acid
	With anhydrous aluminium sulphate; sulfuric acid at 100℃;
	With 3 A molecular sieve; sulfuric acid for 72h; Heating;
	With sulfuric acid Heating;
29.1 g	With thionyl chloride
	With sulfuric acid at 80℃; for 48h;
	With sulfuric acid for 48h; Heating;
	With sulfuric acid Reflux;
	With N-propanesulfonic acid pyridinium hydrogensulfate at 105℃; for 0.333333h; Microwave irradiation;
	With sulfuric acid
	With thionyl chloride at 0℃; for 4h;
	With sulfuric acid for 8h; Reflux;	General method for the synthesis of hydrazides General procedure: Substituted aromatic acid (0.01 mol) was dissolved in 20 ml absolute ethanol added 1 ml conc. H2SO4 and refluxed for 8 h. The two third volume of reaction mixture was removed under reduced pressure and then poured into crushed ice and neutralized with sodium bicarbonate to obtain esters. In the subsequent step equimolar quantity of substituted ester (0.005 mol) and hydrazine hydrate (0.25 ml, 0.005 mol) in ethanol was refluxed for 24 h with stirring. The two third volume of alcohol was removed under reduced pressure and the reaction mixture was poured into the crushed ice. The resultant precipitate was filtered, washed with water and dried. The solid was recrystallized from 25 ml of 90 % ethanol. The purity of the compounds was checked by TLC using toluene-ethyl acetate-formic acid (5:4:1) as mobile phase.
	With sulfuric acid
	With sulfuric acid
	With sulfuric acid Reflux;
	With thionyl chloride for 24h; Reflux;
	With sulfuric acid for 8h; Reflux;	4.1.3 General procedure for the preparation of substituted aromatic ethyl esters (12a-g) General procedure: A mixture of substituted benzoic acids (11a-g) (0.001M, 2.12g) and ethanol (20mL) were heated under reflux until the benzoic acid was dissolved in ethanol then few drops of concentrated H2SO4 was added to the mixture and reflux for 8h. The resulting mixture was cooled to room temperature and a saturated solution of sodium bicarbonate was added to the mixture to neutralise the benzoic acid. The precipitated product was filtered and washed with water and dried. The dried product was recrystallized with ethanol.
	With 1-(4-sulfonic acid)butyl-3-methylimidazolium hydrogen sulfate at 130℃; for 2h;
	With Amberlyst-15	1.1.1 3.1.1.1. Preparation of 2-Hydroxybenzohydrazide(HD2). An ethanol (300 ml) suspension of salicylic acid(13.8 g; 0.1 mol) and strongly acidic ion-exchange resin,Amberlyst-15 (5 g) were stirred with refluxing for three days.Insoluble catalyst was separated by filtration, and washed withethanol (3 20 ml). Combined ethanol filtrates were mixed with hydrazine hydrate (20 ml; 20.5 g; 0.4 mol) and refluxed with slowsolvent distillation using the modified Hickman still apparatus(Scheme 3). After 3 h of refluxing, the volume of the reaction mixturewas reduced to about 50 ml and white precipitate started toform. The white suspension was cooled to room temperature andthen left at 5 C for 1 h. Insoluble product was separated by filtration,washed with ice cold ethanol, and dried on air to give pureproduct (13.2 g; 87%).
	With sulfuric acid for 8 - 12h; Reflux;
	With sulfuric acid In water monomer for 6h; Reflux;	Synthesis of benzohydrazides General procedure: Hydrazides (30-58) were synthesized by one pot conventionalmethod24 Benzoic acid or its derivative (10 mmol) was dissolvedin ethanol (20 mL). Sulfuric acid (3 N, 2 mL) was added and thereaction contents were refluxed for six hours. The reaction wasmonitored with TLC. After the completion of the reaction, the reactionmixture was neutralized by adding solid NaHCO3, and filteredto remove excess of NaHCO3. In the neutralized reaction mixture which contains ethyl ester, hydrazine monohydrate (1.5 mL,3 mmol) was added and refluxed for 3-6 h to complete the reaction.Ethanol and unreacted hydrazine were removed by distillationupto 1/3 volume. The reaction contents were cooled, filteredand recrystallized from methanol to obtain the desired hydrazidecrystals (see Supporting information).
	With ionic liquid based on Keggin (H₃PW₁₂O₄₀) heteroployacid for 0.0333333h; Microwave irradiation; Green chemistry;
	With sulfuric acid
	With sulfuric acid Reflux;	General procedure: We added dense H2SO4 (0.098g, 1mmol) to a solution of substituted benzoic acid (5mmol) in dry ethyl alcohol (10mL). The mixture was heated under reflux until completion (as monitored via TLC), and the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (50mL) and washed with 0.1M Na2CO3, brine, dried and concentrated, respectively. The crude products (intermediate 3) were used directly for the next step.
55.6 kg	With sulfuric acid In water monomer at 110℃; Large scale;	1-4; 1-3 Example 1 Synthesis: 15.0 kg of 95% ethanol, 1.0 kg of sulfuric acid and 50.0 kg of salicylic acid were put into a glass-lined reaction tank, and heated to reflux to about 50% or more (approximately range). When salicylic acid was dissolved, the reflux was stopped, and distillation of the ethanol aqueous solution was started. When the temperature of the reaction system rises to 110 ° C, 95% ethanol was added to the reaction system at a rate of 2.9 L/h (hourly, 0.058 L of ethanol per 1 kg of salicylic acid), and the temperature of the reaction system was controlled to be about 110 ° C. And the ethanol recovery ratio is 60%. The amount of salicylic acid in the reaction system is judged, and if it is required, the addition of ethanol is stopped, and the ethanol distilled between 100-120 ° C is continuously collected. The volume of the glass-lined reaction tank is 50L. The method for judging the balance of salicylic acid in the reaction system is as follows: During the esterification reaction, the concentration of the recovered ethanol aqueous solution is detected. When the ethanol concentration is greater than 90%, a small amount of the esterification reaction sample is taken, and 5.0 mL of sodium carbonate phenolphthalein test solution is added for detection.If the solution is dark red and does not fade within 15 seconds, Then, the requirement to stop adding high concentrations of 95% ethanol. Product cleaning: cooling, the temperature of the reaction system is reduced to below 50 °C, 15 kg of purified water was added to the glass-lined reaction vessel, and the mixture was stirred and washed with water for 20 minutes. The solution was allowed to stand for stratification, and the lower esterification reactant was collected. To the esterification reaction was added 15 kg of a 10% sodium carbonate solution. The mixture was stirred and neutralized for 20 min, left to stand for stratification, and the lower esterification reactant was collected. And continue to wash the esterification reaction until the upper layer of water is nearly neutral with pH test paper. The neutral crude ethyl salicylate was isolated. Product purification: the crude ethyl salicylate is added to a distillation pot for distillation under reduced pressure. Collecting fractions between tower temperatures of 80-125 °C at 0.09 MPa, the ethyl salicylate product was 55.6 kg.
	Heating; Acidic conditions;
	Stage #1: ethanol; 2-hydroxy-1-benzoic acid With thionyl chloride for 4h; Cooling with ice; Stage #2: for 6h; Reflux;
	With sulfuric acid Reflux;	2.1.1.1. General procedure for the Synthesis of (2/3/4) un/substituted ethylbenzoate (2a-2g). General procedure: As presented in Scheme 2, the unsubstituted/substituted aromatic acid compound (1a-1g, 1 mmol) were dissolved in ethanol (15 mL) and stirred for 10 min. Concentrated H2SO4 was added to it and followed by refluxing for 5-6 h. The formationof the product was checked by using TLC in hexane/Ethyl acetate (4:6) [50a]. After completion of the reaction, the reaction mass was gradually cooled to ambient temperature and concentrated by rotary evaporator. Water was added to the residue and extracted by using ethyl acetate. Further, ethyl acetate part (organic layer) was washed by a saturated solution of sodium bicarbonate (to remove the excess of acid) and followed by water and brine washing. The ethyl acetate layer was dried over anhydrous magnesium sulphate, filtered, and distilled to afford a (2a-2g) with 70-80% yield and used for the next step.
	With sulfuric acid at 80℃;
	With sulfuric acid Reflux;	- Route B (R1 = aryl) General procedure: Note: hydrazine and carbon disulphide used during this procedure have to be handled withcaution.The carboxylic compound was first converted into its ethyl ester by refluxing in absoluteethanol in the presence of a few drops of H2SO4. The ester was then treated overnight withhydrazine hydrate (2 to 4 equiv.) without solvent at 120 °C. Evaporation of excess hydrazineyielded the corresponding hydrazide compound. The hydrazide, solubilized in absolute ethanol,was treated with CS2 (5 equiv.) in the presence of KOH (1.7 equiv.) at 85 °C for 3 h. Water wasadded and pH was adjusted to 2-3 with 1N HCl. The formed precipitate was collected byfiltration and washed with water, yielding the 1,3,4-oxadiazol-thione, which was used withoutfurther purification. Finally, the preceding compound was treated with hydrazine hydrate (10equiv.) in absolute ethanol at 100 °C overnight in a sealed tube. After evaporation of excesshydrazine, the residue was purified on a silica gel column to yield the final compound.
	With sulfuric acid for 3h; Reflux;
	With thionyl chloride at 0 - 20℃; for 9h; Reflux;	To a solution of hydroxybenzoic acid (compound 4a orcompound 4 b or compound 4c) (20 mmol) in EtOH (200 mL)at room temperature, was added SOCl2 (40 mmol) in dropwiseat 0 C. The mixture was stirred for 1 h at room temperatureslowly and heated at reflux for 8 h, cooled to roomtemperature. The solvent was removed by rotary evaporation.The residue was dissolved in 50 mL of ethyl acetate.The mixture was washed with water and brine and driedover anhydrous Na2SO4, and concentrated in vacuo. Then,the crude compound 5a-c was used without furtherpurification.
	With sulfuric acid at 78℃; for 2h;
	With sulfuric acid
	With sulfuric acid Reflux;

Reference： [1]Zhao, Long; Huang, Guanxin; Guo, Beibei; Xu, Lijun; Chen, Jie; Cao, Weiguo; Zhao, Gang; Wu, Xiaoyu [Organic Letters, 2014, vol. 16, # 21, p. 5584 - 5587]
[2]Current Patent Assignee: TAIRX - US2012/15908, 2012, A1 Location in patent: Page/Page column 24-25
[3]Fabian, Lucas; Gomez, Matias; Kuran, Juan A. Caturelli; Moltrasio, Graciela; Moglioni, Albertina [Synthetic Communications, 2014, vol. 44, # 16, p. 2386 - 2392]
[4]Location in patent: experimental part Bamoharram, Fatemeh F.; Heravi, Majid M.; Ebrahimi, Javad; Ahmadpour, Ali; Zebarjad, Mojtaba [Cuihua Xuebao/Chinese Journal of Catalysis, 2011, vol. 32, # 5, p. 782 - 788]
[5]Jiang; Hu; Pang; Yuan [Journal of the American Oil Chemists' Society, 1996, vol. 73, # 7, p. 847 - 850]
[6]Location in patent: experimental part Perveen, Shahnaz; Yasmeen, Arfa; Khan, Muhammad Aitmaud; Dar, Ahsana; Jafri, Rehana; Ahmed, Amir [Letters in drug design and discovery, 2010, vol. 7, # 1, p. 14 - 17]
[7]Zhao, Yu Qiang; Zhou, Jie; He, Renze; Wang, Guang Ke; Miao, Lan Xi; Xie, Xiao Guang; Zhou, Ying [Tetrahedron Letters, 2020, vol. 61, # 52]
[8]Current Patent Assignee: GENMEDICA; GENMEDICA THERAPEUTICS SL. - US2012/149769, 2012, A1 Location in patent: Page/Page column 25
[9]Current Patent Assignee: GENMEDICA THERAPEUTICS SL. - WO2013/37985, 2013, A1 Location in patent: Page/Page column 87
[10]Nakanishi, Takayuki; Suzuki, Yuki; Doi, Yoshihiro; Seki, Tomohiro; Koizumi, Hitoshi; Fushimi, Koji; Fujita, Koji; Hinatsu, Yukio; Ito, Hajime; Tanaka, Katsuhisa; Hasegawa, Yasuchika [Inorganic Chemistry, 2014, vol. 53, # 14, p. 7635 - 7641]
[11]Parameshwar; Selvam; Ghashang, Majid; Guhanathan [Oriental Journal of Chemistry, 2017, vol. 33, # 3, p. 1502 - 1512]
[12]Khan, Abdul Majeed; Khaliq, Shaista; Sadiq, Rabia [Bulletin of the Chemical Society of Ethiopia, 2015, vol. 29, # 2, p. 239 - 245]
[13]Location in patent: experimental part Cheng, Kui; Zheng, Qing-Zhong; Qian, Yong; Shi, Lei; Zhao, Jing; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 23, p. 7861 - 7871] Location in patent: experimental part Cheng, Kui; Zheng, Qing-Zhong; Hou, Jin; Zhou, Yang; Liu, Chang-Hong; Zhao, Jing; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 7, p. 2447 - 2455]
[14]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - CN104447585, 2016, B Location in patent: Paragraph 0162; 0163; 0164
[15]Hosangadi, Bhaskar D.; Dave, Rajesh H. [Tetrahedron Letters, 1996, vol. 37, # 35, p. 6375 - 6378]
[16]Schreiner [Justus Liebigs Annalen der Chemie, 1879, vol. 197, p. 13] Goettig [Chemische Berichte, 1876, vol. 9, p. 1474]
[17]Cahours [Annales de Chimie (Cachan, France), 1844, vol. <3> 10, p. 329,336, 353][Justus Liebigs Annalen der Chemie, 1843, vol. 48, p. 65] Baly [Justus Liebigs Annalen der Chemie, 1849, vol. 70, p. 271]
[18]Bogojawlenski; Narbutt [Chemische Berichte, 1905, vol. 38, p. 3348]
[19]Bogojawlenski; Narbutt [Chemische Berichte, 1905, vol. 38, p. 3348]
[20]Kotake; Fujita [Rikagaku Kenkyusho Iho, vol. 1, p. 65][Chemisches Zentralblatt, 1928, vol. 99, # II, p. 1545]
[21]Erhardt, Paul W.; Woo, Chi M.; Anderson, William G.; Gorczynski, Richard J. [Journal of Medicinal Chemistry, 1982, vol. 25, # 12, p. 1408 - 1412]
[22]Parmar, Virinder S.; Kumar, Ajay; Bicht, Kirpal S.; Mukherjee, Shubhasish; Prasad, Ashok K.; Sharma, Sunil K.; Wengel, Jesper; Olsen, Carl E. [Tetrahedron, 1997, vol. 53, # 6, p. 2163 - 2176]
[23]Oikawa; Nakagawa; Nishimura; Ueno; Fujita [Pesticide Science, 1994, vol. 41, # 2, p. 139 - 148]
[24]Bolton, Onas; Kim, Jinsang [Journal of Materials Chemistry, 2007, vol. 17, # 19, p. 1981 - 1988]
[25]Hadj-esfandiari, Narges; Navidpour, Latifeh; Shadnia, Hooman; Amini, Mohsen; Samadi, Nasrin; Faramarzi, Mohammad Ali; Shafiee, Abbas [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6354 - 6363]
[26]Location in patent: experimental part Saha, Ajoy; Kumar, Rajesh; Kumar, Rajendra; Devakumar [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 4, p. 526 - 531] Location in patent: experimental part Saha, Ajoy; Kumar, Rajesh; Kumar, Rajendra; Devakumar [Journal of Heterocyclic Chemistry, 2010, vol. 47, # 4, p. 838 - 845]
[27]Location in patent: experimental part Shi, Hua; Zhu, Wenshuai; Li, Huaming; Liu, Hua; Zhang, Ming; Yan, Yongsheng; Wang, Zhigao [Catalysis Communications, 2010, vol. 11, # 7, p. 588 - 591]
[28]Location in patent: scheme or table Husain, Asif; Naseer, Mohammad A.; Sarafroz, Mohammad [Acta poloniae pharmaceutica, 2009, vol. 66, # 2, p. 135 - 140] Location in patent: scheme or table Cui, Zining; Li, Ying; Ling, Yun; Huang, Juan; Cui, Jingrong; Wang, Ruiqing; Yang, Xinling [European Journal of Medicinal Chemistry, 2010, vol. 45, # 12, p. 5576 - 5584]
[29]Location in patent: experimental part Wang, Jianguo; Tan, Haizhong; Li, Yonghong; Ma, Yi; Li, Zhengming; Guddat, Luke W. [Journal of Agricultural and Food Chemistry, 2011, vol. 59, # 18, p. 9892 - 9900]
[30]Ahsan, Mohamed Jawed; Samy, Jeyabalan Govinda; Khalilullah, Habibullah; Nomani, Md. Shivli; Saraswat, Pankaj; Gaur, Ramakant; Singh, Abhimanyu [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7246 - 7250]
[31]Location in patent: scheme or table Ahmed, Ejaz; Manwar, Muhammad Ramzan; Sharif, Ahsan; Mukhtar-Ul-Hassan; Ahmed, Neman; Malik, Abdul; Mahmood, Zaid; Munawar, Munawar Ali [Journal of the Chemical Society of Pakistan, 2011, vol. 33, # 3, p. 417 - 420]
[32]Du, Qian-Ru; Li, Dong-Dong; Pi, Ya-Zhou; Li, Jing-Ran; Sun, Jian; Fang, Fei; Zhong, Wei-Qing; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297]
[33]Kumar, Pradeep; Narasimhan, Balasubramanian; Ramasamy, Kalavathy; Mani, Vasudevan; Mishra, Rakesh Kumar; Majeed, Abu Bakar Abdul; De Clercq, Erik [Monatshefte fur Chemie, 2013, vol. 144, # 6, p. 825 - 849] Sevaille, Laurent; Gavara, Laurent; Bebrone, Carine; De Luca, Filomena; Nauton, Lionel; Achard, Maud; Mercuri, Paola; Tanfoni, Silvia; Borgianni, Luisa; Guyon, Carole; Lonjon, Pauline; Turan-Zitouni, Gülhan; Dzieciolowski, Julia; Becker, Katja; Bénard, Lionel; Condon, Ciaran; Maillard, Ludovic; Martinez, Jean; Frère, Jean-Marie; Dideberg, Otto; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985]
[34]Chen, Hongfei; Li, Guoning; Zhan, Peng; Guo, Xiuli; Ding, Qian; Wang, Shouxun; Liu, Xinyong [MedChemComm, 2013, vol. 4, # 5, p. 827 - 832]
[35]Rakse, Monika; Karthikeyan, Chandrabose; Deora, Girdhar Singh; Moorthy; Rathore, Vandana; Rawat, Arun K.; Srivastava; Trivedi, Piyush [European Journal of Medicinal Chemistry, 2013, vol. 70, p. 469 - 476]
[36]Tao, Duan-Jian; Wu, Jing; Wang, Zhen-Zhen; Lu, Zhang-Hui; Yang, Zhen; Chen, Xiang-Shu [RSC Advances, 2014, vol. 4, # 1, p. 1 - 7]
[37]Backes, Gregory L.; Jursic, Branko S.; Neumann, Donna M. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3397 - 3407]
[38]Ahsan, Mohamed Jawed; Choudhary, Kavita; Jadav, Surender Singh; Yasmin, Sabina; Ansari, Md. Yousuf; Sreenivasulu, Reddymasu [Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 4166 - 4180]
[39]Mehr-Un-Nisa; Munawar, Munawar A.; Chattha, Fauzia A.; Kousar, Samina; Munir, Jawaria; Ismail, Tayaba; Ashraf, Muhammad; Khan, Misbahul A. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 6014 - 6024]
[40]Bamoharram, Fatemeh F.; Heravi, Majid M.; Ebrahimi, Javad; Tavakoli-Hoseini, Nilofar [Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 2014, vol. 44, # 1, p. 36 - 42]
[41]Zhou, Wen-Juan; Zhang, Li; Xiao, Wei; Chen, He-Ju; Wu, Wen-Neng; Ouyang, Gui-Ping [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1423 - 1429]
[42]He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5652 - 5661]
[43]Current Patent Assignee: GUANGZHOU BAIYUNSHAN PHARMACEUTICAL HOLDINGS CO., LTD. - CN110283072, 2019, A Location in patent: Paragraph 0047-0076
[44]Kaproń, Barbara; Łuszczki, Jarogniew J.; Siwek, Agata; Karcz, Tadeusz; Nowak, Gabriel; Zagaja, Mirosław; Andres-Mach, Marta; Stasiłowicz, Anna; Cielecka-Piontek, Judyta; Kocki, Janusz; Plech, Tomasz [Bioorganic Chemistry, 2020, vol. 94]
[45]Brandão, Paula; Das, Debasis; Félix, Vítor; Ghosh, Milan; Ghosh, Subhasis; Hira, Sumit Kumar; Khanra, Somnath; Manna, Partha Partim; Paladhi, Ankush; Ta, Sabyasachi [Chemical Communications, 2020, vol. 56, # 48, p. 6563 - 6566]
[46]Dige, Nilam C.; Hassan, Mubashir; Lee, Ki Hwan; Mahajan, Prasad G.; Raza, Hussain; Seo, Sung-Yum; Vanjare, Balasaheb D. [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2020, vol. 241]
[47]Begam, Hasina Mamataj; Jana, Ranjan; Manna, Kartic; Samanta, Krishanu [Organic Letters, 2020, vol. 22, # 19, p. 7443 - 7449]
[48]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]
[49]Eissa, Ibrahim H.; El-Helby, Abdel-Ghany A.; Mahdy, Hazem A.; Khalifa, Mohamed M.; Elnagar, Hamdy A.; Mehany, Ahmed B.M.; Metwaly, Ahmed M.; Elhendawy, Mostafa A.; Radwan, Mohamed M.; ElSohly, Mahmoud A.; El-Adl, Khaled [Bioorganic Chemistry, 2020, vol. 105] El-Adl, Khaled; El-Helby, Abdel-Ghany A.; Ayyad, Rezk R.; Mahdy, Hazem A.; Khalifa, Mohamed M.; Elnagar, Hamdy A.; Mehany, Ahmed B.M.; Metwaly, Ahmed M.; Elhendawy, Mostafa A.; Radwan, Mohamed M.; ElSohly, Mahmoud A.; Eissa, Ibrahim H. [Bioorganic and Medicinal Chemistry, 2021, vol. 29]
[50]Li, Hong-Lian; Li, Wei-Ya; Lu, Xin-Hua; Ma, Ying; Tang, Xue; Wang, Run-Ling; Wu, Jing-Wei; Zhang, Huan; Zheng, Zhi-Hui [Journal of Biomolecular Structure and Dynamics, 2020, vol. 38, # 18, p. 5338 - 5348]
[51]Liu, Jie; Zhang, Guang-Yu; Zhang, Zhe; Li, Bo; Chai, Fei; Wang, Qi; Zhou, Zi-Dan; Xu, Ling-Ling; Wang, Shou-Kai; Jin, Zhen; Tang, You-Zhi [Bioorganic Chemistry, 2021, vol. 112]
[52]Yousef, Reda G.; Sakr, Helmy M.; Eissa, Ibrahim H.; Mehany, Ahmed. B. M.; Metwaly, Ahmed M.; Elhendawy, Mostafa A.; Radwan, Mohamed M.; ElSohly, Mahmoud A.; Abulkhair, Hamada S.; El-Adl, Khaled [New Journal of Chemistry, 2021, vol. 45, # 36, p. 16949 - 16964]
[53]Hassan, Mubashir; Hwan Lee, Ki; Ja Kim, Song; Raza, Hussain; Seok Eom, Young; Vanjare, Balasaheb D. [Bioorganic and Medicinal Chemistry, 2022, vol. 63]

3
[ 75-44-5 ]
[ 118-61-6 ]
[ 208928-82-9 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; benzene
	With dimethyl amine In toluene at 0℃; for 2h; Inert atmosphere;	1.AD Ethyl 2-r(chlorocarbony0oxy1benzoate - General Procedure AD (acid chloride from carboxylic acid) General procedure: Ethyl 2-r(chlorocarbony0oxy1benzoate - General Procedure AD (acid chloride from carboxylic acid) The carboxylic acid (Ethyl 2-hydroxybenzoate) (1 eq) in toluene was cooled to 0 °C, N, N-dimethyl amine (leq) was added, phosgene (1 eq) was added dropwise and stirred at same temperature for 2 h. The solid was filtered off and the filtrate was concentrated and used as reagent without further purification.
	With quinoline; benzene

Reference： [1]Einhorn; Rothlauf [Justus Liebigs Annalen der Chemie, 1911, vol. 382, p. 263]
[2]Current Patent Assignee: GILEAD SCIENCES INC - WO2014/131777, 2014, A1 Location in patent: Page/Page column 150
[3]Current Patent Assignee: Einhorn - DE224108, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1088][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1088]

4
[ 143-19-1 ]
[ 118-61-6 ]
2-oleoyloxy-benzoic acid ethyl ester [ No CAS ]

Reference： [1]Patent: DE206056,

5
[ 118-61-6 ]
[ 74-88-4 ]
[ 7335-26-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide
	With sodium hydride In tetrahydrofuran at 0℃;	131 To O0C solution of ethyl salicylate (1.66g, lOmmol) in 20ml THF was added NaH (60% 0.4g, lOmmol) in several potion, then iodomethane (1.42g, lOmmol) was added. The solution was allowed warm up and stirred for over night. The reaction mixture was quenched with saturated aqueous NH4Cl (4OmL), extracted with dimethyl ether (3 x 25mL) and washed with brine. The organic phase was dried over Na2SO4, concentrated in vacuo and chromatographed on silica gel using an ISCO single channel system (Hexane/EtOAc = 10/0 to 9/1) to give product ethyl 2-methoxybenzoate as clear oil. 1H NMR (CDCl3, 500 MHz) δ 7.79-7.77 (m, IH), 7.44-7.42 (m, IH), 6.98-6.95 (m, 2H), 4.37-4.33 (q. 2H), 3.88 (s, 3H), 1.38-1.35 (t, 3H).

Reference： [1]Cahours [Justus Liebigs Annalen der Chemie, 1854, vol. 92, p. 315] Graebe [Justus Liebigs Annalen der Chemie, 1866, vol. 139, p. 141]
[2]Current Patent Assignee: MERCK & CO INC - WO2006/14918, 2006, A2 Location in patent: Page/Page column 81

6
[ 118-61-6 ]
[ 37540-59-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With perchloric acid; dihydrogen peroxide; C₁₆H₁₀N₄O₄^(4-)C₃H₇NO6Na⁽¹⁺⁾2OV⁽³⁺⁾2O^(2-)*4HO^(1-); potassium bromide In water at 20℃; for 0.5h;	2.7 General procedure for oxidative bromination General procedure: Salicylaldehyde (0.24g, 2mmol) was taken in a 50mL round bottom flask maintained at 0°C, to this added KBr (0.47g, 4mmol) in 5mL water followed by the addition of 30% H2O2 (1.70g, 15mmol). To this reaction mixture, 2.5mol percent of the complex (1) or (4) (0.05mmol) and 70% HClO4 (0.14g, 1mmol) were added and stirred at 0°C. An additional 1mmol of 70% HClO4 was added in three equal portions at an interval of 10min into the reaction mixture. A light brown solid precipitate was obtained, which was extracted in CH2Cl2 and dried. The crude solid was recrystallized by dissolved in methanol and further purified by silica column chromatography. The brominated products were confirmed by IR and 1H NMR spectroscopies. The 1H NMR spectra of the brominated products are given in the supporting information.
86%	With perchloric acid; [(CH₃)₂NH₂]₂[(VO₂)₂(slox)].2H₂O; dihydrogen peroxide; potassium bromide In water at 0℃; for 0.5h;	3.5. General experiment for oxidative bromination General procedure: Salicylaldehyde (0.24 g, 2 mmol) was taken in a 50 mL roundbottom flask maintained at 0 C, KBr (0.47 g, 4 mmol) dissolvedin 5 mL water was added, followed by the addition of 30% H2O2(1.70 g, 15 mmol). To this reaction mixture, the vanadium(V) complexes1-3 (0.05 mmol) and 70% HClO4 (0.14 g, 1 mmol) wereadded and the reaction mixture was stirred at 0 C. An additional1 mmol of 70% HClO4 was further added in three equal portionsafter every 10 minutes, with continuous stirring. A light brownsolid product was obtained which was separated using a separating funnel. The crude product thus obtained was then purifiedby column chromatography to afford the desired product. TheNMR spectra of the bromination products are given in the Supportinginformation.
86%	With perchloric acid; dihydrogen peroxide; C₁₄H₉BrN₂O₄V^(1-); potassium bromide In water at 0 - 24℃; for 0.583333h;

85%	With perchloric acid; C₁₆H₈Cl₂N₄O₈V₂^(2-)4H₂O2C₂H₇N*2H⁽¹⁺⁾; dihydrogen peroxide; potassium bromide In water at 0 - 20℃; for 0.5h;
84%	With trimethylsilyl bromide; bis(4-chlorophenyl)sulfoxide In acetonitrile at 35℃; for 12h; Inert atmosphere; regioselective reaction;
80%	With trimethylsilyl bromide; bis(4-chlorophenyl)sulfoxide In acetonitrile at 35℃; for 12h; Inert atmosphere;	12 Example 12 Preparation of ethyl 2-hydroxy 5-bromobenzoate by ethyl 2-hydroxybenzoate and trimethylbromosilane Adding 2-hydroxybenzoic acid ethyl ester to the tubular reactor (83.0 mg, 0.50 mmol), Trimethylbromosilane (84.2 mg, 0.55 mmol, 1.1 equiv.), Di-(4-chlorophenyl)sulfoxide (148.5 mg, 0.55 mol) and acetonitrile (1.0 mL), It was then evacuated, protected with nitrogen and reacted at 35 ° C for 12 h. After GC-MS monitors the reaction, it is filtered. The filter cake was washed with a small amount of cold acetonitrile. The recovered filter cake is bis-(4-chlorophenyl) sulfide.1M sodium hydroxide (0.6 mL) was added to the filtrate. Then it was transferred to a separatory funnel and extracted with ethyl acetate 5 mL3, and the organic layer was combined. After spinning, it is combined with the above-mentioned filter cake bis-(4-chlorophenyl) sulfide.a mixture of bis-(4-chlorophenyl) sulfoxide (remaining reaction) and bis-(4-chlorophenyl) sulfide (reacted by reaction), The mixture is then completely converted to bis-(4-chlorophenyl)sulfoxide via oxidation. It can be used as a bromination reaction of the next phenol compound as an activator (total recovery is 90%). The obtained aqueous phase was extracted, and 1 M diluted hydrochloric acid was added to adjust the pH to 1, Then add ethyl acetate 5 mL3 again to extract and combine the organic phases. Dry over anhydrous sodium sulfate, spin dry to give the product 2-hydroxy 5-bromobenzoic acid ethyl ester, The isolated yield was 80% (product purity > 95%) (selectivity 98/2).
	With chloroform; bromine

Reference： [1]Borthakur, Rosmita; Dhanpat, Shobha A.; Kumar, Arvind; Kurbah, Sunshine D.; Lal, Ram A.; Syiemlieh, Ibanphylla [Inorganica Chimica Acta, 2021, vol. 515]
[2]Syiemlieh, Ibanphylla; Asthana, Mrityunjaya; Kurbah, Sunshine D.; Lal, Ram A. [Polyhedron, 2019, vol. 170, p. 202 - 216]
[3]Kurbah, Sunshine Dominic; Lal, Ram A. [New Journal of Chemistry, 2020, vol. 44, # 14, p. 5410 - 5418]
[4]Syiemlieh, Ibanphylla; Asthana, Mrityunjaya; Lal, Ram A. [Applied Organometallic Chemistry, 2019, vol. 33, # 8]
[5]Ma, Xiantao; Yu, Jing; Jiang, Mengyuan; Wang, Mengyu; Tang, Lin; Wei, Mengmeng; Zhou, Qiuju [European Journal of Organic Chemistry, 2019, vol. 2019, # 28, p. 4593 - 4596]
[6]Current Patent Assignee: XINYANG NORMAL UNIVERSITY - CN109761759, 2019, A Location in patent: Paragraph 0043; 0044; 0045
[7]Freer [Journal fur praktische Chemie (Leipzig 1954), 1893, vol. <2> 47, p. 240,242]

7
[ 118-61-6 ]
[ 56923-38-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; copper

Reference： [1]Hirwe; Jadhav; Chakradeo [Journal of the American Chemical Society, 1935, vol. 57, p. 101]

8
[ 118-61-6 ]
[ 936-02-7 ]

Yield	Reaction Conditions	Operation in experiment
99.1%	With hydrazine hydrate; In ethanol; at 70℃; for 0.00111111h;	Ethyl salicylate is dissolved in ethanol, Prepare a 2.5 mol/L ethanol solution for use. 80% by mass of hydrazine hydrate is dissolved in ethanol, A 2 mol/L solution was prepared for use. An ethanol solution of ethyl salicylate was injected into the microchannel reactor or the pipeline reactor through a metering pump at a flow rate of 20 ml/min. The hydrazine hydrated ethanol solution was injected into the microchannel reactor or pipeline reactor through another metering pump at a flow rate of 25 ml/min. React at 70 C for 4 seconds, Flow out of the microchannel reactor or pipeline reactor, Collecting reaction materials, Obtaining a white powdery crystalline product, Yield 99.1%, The content is 99.8%. The reaction mother liquid ethanol is filtered and applied.
85%	With hydrazine hydrate; In ethanol; water;Reflux;	General procedure: Hydrazides (30-58) were synthesized by one pot conventionalmethod24 Benzoic acid or its derivative (10 mmol) was dissolvedin ethanol (20 mL). Sulfuric acid (3 N, 2 mL) was added and thereaction contents were refluxed for six hours. The reaction wasmonitored with TLC. After the completion of the reaction, the reactionmixture was neutralized by adding solid NaHCO3, and filteredto remove excess of NaHCO3. In the neutralized reaction mixture which contains ethyl ester, hydrazine monohydrate (1.5 mL,3 mmol) was added and refluxed for 3-6 h to complete the reaction.Ethanol and unreacted hydrazine were removed by distillationupto 1/3 volume. The reaction contents were cooled, filteredand recrystallized from methanol to obtain the desired hydrazidecrystals (see Supporting information).
70%	With hydrazine hydrate; In ethanol; at 20 - 80℃; for 2h;	Hydrazine monohydrate (20 ml) wasadded to a solution of ethyl 2-hydroxybenzoate(4 g, 0.024 mmol) in ethanol (100 ml) at roomtemperature and the reaction mixture was heatedto 80C and and stirred for 2h at same temperature.After completion of the reaction (TlC monitoring),ethanol was concentrated. To that residue ice coldwater was added and stirred for 30 min until a whitecolor solid was precipitated. The white solid wasfltered and dried under vacuum (Yield 70%). 1HNMR(400 MHz, DMSO-d6 ): d = 10.10 (s,1H, OH), 7.78-7.81 (dd, J = 7.6, 1.6 Hz, 1H), 7.36 (td, J = 7.6,1.6 Hz, 1H), 6.83-6.90 (m, 2H), 4.71 (s, 2H, NH2); IR:3274 (N-H, amide), 1652, 1530, 1372, 1304, 1245,1146, 1033, 957, 756 cm-1.

	With hydrazine hydrate; In ethanol; for 24h;Reflux;	General procedure: Substituted aromatic acid (0.01 mol) was dissolved in 20 ml absolute ethanol added 1 ml conc. H2SO4 and refluxed for 8 h. The two third volume of reaction mixture was removed under reduced pressure and then poured into crushed ice and neutralized with sodium bicarbonate to obtain esters. In the subsequent step equimolar quantity of substituted ester (0.005 mol) and hydrazine hydrate (0.25 ml, 0.005 mol) in ethanol was refluxed for 24 h with stirring. The two third volume of alcohol was removed under reduced pressure and the reaction mixture was poured into the crushed ice. The resultant precipitate was filtered, washed with water and dried. The solid was recrystallized from 25 ml of 90 % ethanol. The purity of the compounds was checked by TLC using toluene-ethyl acetate-formic acid (5:4:1) as mobile phase.
	With hydrazine hydrate; In ethanol; for 6.5h;Reflux;	General procedure: A mixture of substituted ethyl benzoate (12a-g) (0.1M) and hydrazine hydrate (0.3M) was heated under reflux for 30min. Ethanol (20mL) was added to the refluxing mixture as a solvent in order to homogenize the solution, the resulting mixture was further allowed for 6h. Excess of ethanol was distilled out and the content was allowed to cool. The crystals formed were filtered and washed thoroughly with water and dried.
13.2 g	With hydrazine hydrate; In ethanol; for 3h;Reflux;	An ethanol (300 ml) suspension of salicylic acid(13.8 g; 0.1 mol) and strongly acidic ion-exchange resin,Amberlyst-15 (5 g) were stirred with refluxing for three days.Insoluble catalyst was separated by filtration, and washed withethanol (3 20 ml). Combined ethanol filtrates were mixed with hydrazine hydrate (20 ml; 20.5 g; 0.4 mol) and refluxed with slowsolvent distillation using the modified Hickman still apparatus(Scheme 3). After 3 h of refluxing, the volume of the reaction mixturewas reduced to about 50 ml and white precipitate started toform. The white suspension was cooled to room temperature andthen left at 5 C for 1 h. Insoluble product was separated by filtration,washed with ice cold ethanol, and dried on air to give pureproduct (13.2 g; 87%).
	With hydrazine hydrate; In ethanol; for 5h;Reflux;	General procedure: 5mL of hydrazine monohydrate (80%) was added to a solution of intermediate 3 (5mmol) in ethanol (5mL). The reaction mixture was maintained under reflux for 5h. was then concentrated under reduced pressure and the resulting solid was collected by filtration, washed with cold water and dried to give the desired intermediate 4 as a white solid.
	With hydrazine hydrate; In ethanol; at 75 - 80℃; for 4h;	1mmolEthyl ortho-hydroxybenzoate5 mmol hydrazine hydrate in 30 ml absolute ethanol,Heat at 75-80C for 4hAfter cooling to room temperature,Precipitation of solids,The solids are washed with anhydrous ethanol.The dried intermediate compound was used directly in the next step.The intermediate is in absolute ethanol,75-80CNext and neighborsHydroxynaphthalene formaldehydeMolar ratio 1..1-1.2 reaction 4h,After cooling, the precipitated solid is filtered off with suction and washed with large amounts of water and absolute ethanol in that order.Drying gave pale yellow solid P, yield 85%
	With hydrazine; In ethanol; at 75 - 80℃; for 4h;	Pyrene derivatives preparation of P: will be 1 mm O-hydroxy benzoic acid ethyl ester with its 5 times the molar amount of hydrazine hydrate in 30 ml of anhydrous alcohol, 75 - 80 C reflux 4 h, after cooling to room temperature, precipitate solid filtering, solid and then by absolute ethanol washing, drying the resulting intermediate compound is directly used for the next step. 1 Mm intermediate in anhydrous alcohol, 75 - 80 C under pipi formaldehyde to with the molar ratio of 1:1 reaction 4 h, after cooling the separated solid filtering, are large quantities of water and anhydrous ethanol washing, drying, a yellow solid pure product P, yield 85% (see Figure 1 and Figure 2).
	With hydrazine hydrate; for 5h;Reflux;	2.2.2 Salicyloylhydrazine (2-OH-C6H4CO-NHNH2) An equimolar mixture of ethylsalicylate and hydrazine hydrate was refluxed for 5?h where after the white solid mass obtained was recrystallized twice from hot water (12). Melting point 146.

Reference： [1]Patent: CN109574870,2019,A .Location in patent: Paragraph 0078-0080
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6014 - 6024
[3]RSC Advances,2014,vol. 4,p. 58895 - 58901
[4]Oriental Journal of Chemistry,2017,vol. 33,p. 1502 - 1512
[5]Chemical Communications,2020,vol. 56,p. 6563 - 6566
[6]Chemisches Zentralblatt,1904,vol. 75,p. 1493
[7]Journal fur praktische Chemie (Leipzig 1954),1981,vol. 323,p. 360 - 366
[8]Journal of the Indian Chemical Society,1984,vol. 61,p. 363 - 364
[9]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2006,vol. 64,p. 809 - 815
[10]Tetrahedron,2008,vol. 64,p. 1860 - 1867
[11]Acta poloniae pharmaceutica,2009,vol. 66,p. 135 - 140
[12]Journal of Chemical Research,2009,p. 114 - 119
[13]European Journal of Medicinal Chemistry,2009,vol. 44,p. 3340 - 3344
[14]Pakistan Journal of Scientific and Industrial Research,2009,vol. 52,p. 312 - 315
[15]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2010,vol. 49,p. 526 - 531
[16]Journal of Heterocyclic Chemistry,2010,vol. 47,p. 838 - 845
[17]European Journal of Medicinal Chemistry,2010,vol. 45,p. 5576 - 5584
[18]Journal of Agricultural and Food Chemistry,2011,vol. 59,p. 9892 - 9900
[19]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7246 - 7250
[20]Medicinal Chemistry Research,2011,vol. 20,p. 47 - 54
[21]Medicinal Chemistry,2012,vol. 8,p. 705 - 710
[22]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2286 - 2297
[23]Journal of Structural Chemistry,2012,vol. 53,p. 866 - 875
Zhurnal Strukturnoi Khimii,2012,vol. 53,p. 887 - 895,9
[24]Monatshefte fur Chemie,2013,vol. 144,p. 825 - 849
[25]Journal of the Chemical Society of Pakistan,2013,vol. 35,p. 929 - 937
[26]European Journal of Medicinal Chemistry,2013,vol. 70,p. 469 - 476
[27]Inorganic Chemistry Communications,2013,vol. 36,p. 199 - 205
[28]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3397 - 3407
[29]Journal of Molecular Structure,2015,vol. 1100,p. 105 - 115
[30]RSC Advances,2015,vol. 5,p. 75187 - 75194
[31]Medicinal Chemistry Research,2015,vol. 24,p. 4166 - 4180
[32]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 1423 - 1429
[33]ChemMedChem,2017,vol. 12,p. 972 - 985
[34]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5652 - 5661
[35]Patent: CN107759489,2018,A .Location in patent: Paragraph 0021-0023
[36]Patent: CN107778196,2018,A .Location in patent: Paragraph 0022-0024
[37]Journal of Molecular Structure,2018,vol. 1166,p. 79 - 90
[38]Bioorganic Chemistry,2020,vol. 94
[39]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2020,vol. 241

9
[ 20782-91-6 ]
[ 118-61-6 ]
[ 88796-66-1 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1983,vol. 48,p. 2682 - 2692

10
[ 506-68-3 ]
[ 118-61-6 ]
[ 1134-11-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With triethylamine In acetone at 20℃; Cooling with ice;	1 Compound (I'-1): To a mixture of 1.5 g (9.03 mmole) of ethyl salicylate, 0.96 g (9.03 mmole) of triethylamine and 30 ml of acetone was added dropwise a solution of 0.96 g of cyanogen bromide in acetone (5 ml) under ice-cooling, and the mixture was stirred at room temperature for 18 hours. The reaction solution was concentrated under reduced pressure, and water and saturated NaHCO3 were added to the residue, and extracted with ethyl acetate. The organic layer was washed with brine, dehydrated with anhydrous sodium sulfate, and filtered, and the solvent was concentrated under reduced pressure. The residue was purified by silicagel columnchromatography (n-hexane : ethyl acetate = 4 : 1) to give 0.73 g (42%) of a title compound as a yellow liquid. 1H-NR(CDCl3): δ(ppm) 1.42 (3H, t, J=7.0Hz), 4.43 (2H, q, J=7.0Hz), 7.42 (1H, dt, J=7.0, 1.0Hz), 7.57 (1H, dd, J=9.0, 1.0Hz), 7.66 (1H, dt, J=7.5, 2.0Hz), 8.02 (1H, dd, J=7.5, 2.0Hz)
	With triethylamine In acetone at 0℃;

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD.; INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP2208728, 2010, A1 Location in patent: Page/Page column 32
[2]Hedayatullah; Lion; Pailler [Journal of Heterocyclic Chemistry, 1991, vol. 28, # 1, p. 133 - 137]

11
[ 72593-77-2 ]
[ 118-61-6 ]
[ 147894-71-1 ]

Yield	Reaction Conditions	Operation in experiment
44%	With potassium carbonate In N,N-dimethyl-formamide at 100℃;

Reference： [1]Thaisrivongs; Turner; Strohbach; TenBrink; Tarpley; McQuade; Heinrikson; Tomasselli; Hui; Howe [Journal of Medicinal Chemistry, 1993, vol. 36, # 8, p. 941 - 952]

12
[ 118-61-6 ]
[ 4232-27-3 ]
[ 529-68-0 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1991,p. 1901 - 1908

13
[ 118-61-6 ]
[ 528-15-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydrogencarbonate; N,N,N-trimethylbenzenemethanaminium dichloroiodate In methanol; dichloromethane for 7h; Ambient temperature;
78%	With iodine; silver sulfate In ethanol at 20℃;

Reference： [1]Kajigaeshi, Shoji; Kakinami, Takaaki; Yamasaki, Hiromichi; Fujisaki, Shizuo; Kondo, Manabu; Okamoto, Tsuyoshi [Chemistry Letters, 1987, p. 2109 - 2112]
[2]Lin, Wenwei; Sapountzis, Ioannis; Knochel, Paul [Angewandte Chemie - International Edition, 2005, vol. 44, # 27, p. 4258 - 4261]

14
[ 93-89-0 ]
[ 118-61-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	With oxone; Ru(p-cymene)(diBrbpy)(MesCO<SUB>2</SUB>); trifluoroacetic acid; trifluoroacetic anhydride In 1,2-dichloro-ethane at 85℃; for 6h; Sealed tube; Green chemistry; regioselective reaction;	General procedure for ruthenium-catalyzed ortho-hydroxylation of aryl esters General procedure: The Ru(MesCO2)(L) (p-cymene) [L- 2,2’-bypyridine or 4,4’-dibromobipyridine] (2.5 mol%), oxidant (2.0 eq) and ester (1.0 eq) were added to a sealed tube. Following that, trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA) in the ratio of 0.6 ml: 0.4 were added. The reaction mixture was kept on a pre-heated bath at 110°C and stirred until its completion. It was continuously monitored by TLC. Ice water was added to quench the reaction mixture and it was extracted with dichloromethane. The organic layer was dried over Na2SO4 and rota-evaporated. Finally the residue was purified by silica gel column chromatography to give corresponding products.
73%	With [Ru(p-cymene)Cl₂]2; Selectfluor; trifluoroacetic acid; trifluoroacetic anhydride at 85℃; for 7.5h;
69%	With palladium diacetate; N-fluoropyridinium tetrafluoroborate; trifluoroacetic acid; trifluoroacetic anhydride at 90℃; for 8h; Sealed tube; regioselective reaction;

59%	With dirhodium tetraacetate; dipotassium peroxodisulfate; trifluoroacetic acid; trifluoroacetic anhydride at 90℃; for 9h; Sealed tube; regioselective reaction;
51%	With dipotassium peroxodisulfate; palladium diacetate; trifluoroacetic acid; trifluoroacetic anhydride regioselective reaction;
	(i) CF₃CO₂Na, CF₃CO₂H, MeNO₂, (electrochemical oxidation), (ii) aq. NaHCO₃; Multistep reaction;
	Multi-step reaction with 2 steps 1: 6,6'-diphenyl-2,2'-bipyridine; (1,5-cyclooctadiene)(methoxy)iridium(I) dimer / hexane / 100 °C / Inert atmosphere; Glovebox; Microwave irradiation 2: oxone / water; acetone / 2 h / 0 - 20 °C

Reference： [1]Shome, Sanchari; Singh, Surya Prakash [Tetrahedron Letters, 2017, vol. 58, # 38, p. 3743 - 3746]
[2]Yang, Yiqing; Lin, Yun; Rao, Yu [Organic Letters, 2012, vol. 14, # 11, p. 2874 - 2877]
[3]Shan, Gang; Yang, Xinglin; Ma, Linlin; Rao, Yu [Angewandte Chemie - International Edition, 2012, vol. 51, # 52, p. 13070 - 13074][Angew. Chem., 2012, vol. 124, # 52, p. 13247 - 13251,5]
[4]Shan, Gang; Han, Xuesong; Lin, Yun; Yu, Shanyou; Rao, Yu [Organic and Biomolecular Chemistry, 2013, vol. 11, # 14, p. 2318 - 2322]
[5]Rao, Yu [Synlett, 2013, vol. 24, # 19, p. 2472 - 2476]
[6]So,Y.H.; Miller,L.L. [Synthesis, 1976, p. 468 - 469]
[7]Hoque, Md Emdadul; Dey, Sayan; Mahamudul Hassan, Mirja Md; Chaturvedi, Jagriti; Guria, Saikat; Das, Jaitri; Roy, Brindaban; Chattopadhyay, Buddhadeb [Tetrahedron Chem, 2022, vol. 3]

15
[ 118-61-6 ]
[ 89-73-6 ]

Reference： [1]Bulletin de la Societe Chimique de France,1970,p. 2573 - 2580

16
[ 109-65-9 ]
[ 118-61-6 ]
[ 289894-50-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 3h;
	With potassium carbonate In acetone
	With potassium carbonate In butanone for 48h; Heating / reflux;	32 Example 32: 2-Butoxy-benzoic acid (Compound 29): Under N2, the mixture of ethyl salicylate (4.16 g, 25 mmol), butyl bromide (4.80 g, 3.77 ml, 35 mmol) and potassium carbonate (4.15 g, 30 mmol) in dry 2-Butanone (100 ml) was heated to reflux for 48h. After the reaction mixture cooled down to 250C, the suspended inorganic salt was removed by filtration. The concentration of the resulting solution by rotary evaporation yielded pale yellowish syrup, which was then mixed with 2N NaOH (18 ml, 36 mmol) and EtOH (30 ml). After this mixture was stirred for 2h at 5O0C, ethanol was removed at reduced pressure. After the aqueous solution was acidified by 6N HCl to pH 2 at 50C, the mixture was extracted with Et2O (50 ml x 3). The organic phase was combined and washed with water (10 ml x 2) respectively. The ether extract was dried with anhydrous sodium sulfate and then concentrated to give 2-Butoxy-benzoic acid as oil (3.4Og, 17.5 mmol), which was then treated with of lM sodium trimethylsilanolate (17.0 ml, 17.0 mmol) to give Sodium 2-allyloxy-6-methyJ-benzoate (3.53g, 65.3%) as white powder.1H-NMR (400 MHz, D2O): 7.22 (m, 2 arom. H); 6.93 (m, 2 arom. H); 3.94 (t, CH3CH2CH2CH2O); 1.59 (m, CH3CH2CH2CH2O); 1.32 (m, CH3CH2CH2CH2O); 0.78 (t, CH3CH2CH2CH2O). 13C-NMR (IOO MHz1 D2O): 176.54 (-C=O); 154.93; 130.10; 129.81; 127.85; 120.82; 114.13; 69.26; 30.64; 18.68; 13.21.

Reference： [1]Chung, De Michael; Nowick, James S. [Journal of the American Chemical Society, 2004, vol. 126, # 10, p. 3062 - 3063]
[2]Sadashiva, Bukkinakere K.; Prasad, Veena [Journal of the Chemical Society. Perkin transactions II, 1996, # 4, p. 755 - 760]
[3]Current Patent Assignee: NOVO NORDISK A/S - WO2008/116141, 2008, A1 Location in patent: Page/Page column 41-42

17
[ 74-96-4 ]
[ 118-61-6 ]
[ 6290-24-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In acetone

Reference： [1]Sadashiva, Bukkinakere K.; Prasad, Veena [Journal of the Chemical Society. Perkin transactions II, 1996, # 4, p. 755 - 760]

18
[ 78-71-7 ]
[ 118-61-6 ]
C₂₃H₂₆O₇ [ No CAS ]

Reference： [1]Analytical Chemistry,1997,vol. 69,p. 3002 - 3007

19
[ 100-39-0 ]
[ 118-61-6 ]
[ 63888-93-7 ]

Yield	Reaction Conditions	Operation in experiment
94.71%	With potassium carbonate In acetonitrile for 8h; Reflux; Inert atmosphere;	II.B.7.B To a solution of 68 (5.8 g, 34.9 mmol) in CH3CN (150 ml) was added K2CO3 (10.6 g, 76.8 mmol). The mixture was added benzyl bromide (6.57 g, 38.39 mmol) and refluxed for 8 h under N2 atmosphere. The reaction mixture was cooled to 25° and poured into H2O (500 ml), and then extracted with CH2Cl2. The organic layer was washed with H2O, dried over MgSO4 and evaporated. The crude products were purified by distillation to give 73 as colorless liquid. (8.5 g, 33.2 mmol). Yield: 94.71%; MS (EI, 70 eV): m/z 256.3 (M+); 1H-NMR (CDCl3, 200 MHz): δ 1.33=(t, J=7.2 Hz, 3H), 4.35 (q, =7.2, 7.0 Hz, 2H), 5.15 (s, 2H), 7.00 (d, =8.0 Hz, 2H), 7.32-7.45 (m, 5H), 7.49 (d, J=8.2 Hz, 1H), 7.82 (dd, J=8.2, 1.8 Hz, 1H); 13C-NMR (CDCl3, 50 MHz) δ: 166.60, 158.01, 136.77, 133.25, 131.69, 128.49, 127.80, 126.99, 121.20, 120.56, 113.75, 70.57, 60.93, 14.29; Anal. Calcd for C16H16O3: C, 74.98; H, 6.29.
89.7%	With potassium hydroxide In dimethyl sulfoxide at 45℃; for 5h;
	With potassium carbonate

Reference： [1]Current Patent Assignee: TAIRX - US2012/15908, 2012, A1 Location in patent: Page/Page column 25
[2]Oikawa; Nakagawa; Nishimura; Ueno; Fujita [Pesticide Science, 1994, vol. 41, # 2, p. 139 - 148]
[3]Manna, Kartic; Begam, Hasina Mamataj; Jana, Ranjan [Synthesis, 2022, vol. 55, # 10, p. 1543 - 1552]

20
[ 67-66-3 ]
[ 7726-95-6 ]
[ 118-61-6 ]
[ 37540-59-3 ]

Reference： [1]Freer [Journal fur praktische Chemie (Leipzig 1954), 1893, vol. <2> 47, p. 240,242]

21
[ 100-51-6 ]
[ 118-61-6 ]
[ 118-58-1 ]

Reference： [1]Angewandte Chemie - International Edition,2001,vol. 40,p. 3672 - 3674

22
[ 118-61-6 ]
[ 71-36-3 ]
[ 2052-14-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With di(n-butyl)tin oxide In methanol for 5h; Heating;

Reference： [1]Baumhof, Patrick; Mazitschek, Ralph; Giannis, Athanassios [Angewandte Chemie - International Edition, 2001, vol. 40, # 19, p. 3672 - 3674]

23
[ 358-23-6 ]
[ 118-61-6 ]
[ 179538-97-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydride In hexane; dichloromethane at -78 - 0℃; for 18.5h;
99%	With pyridine In dichloromethane at 20℃; for 0.5h;
95%	With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;

90%	Stage #1: 2-hydroxy-benzoic acid ethyl ester With sodium hydride In hexane; dichloromethane; mineral oil at 0℃; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In hexane; dichloromethane; mineral oil at -78℃; Inert atmosphere;
87 %	With triethylamine In dichloromethane at 0 - 20℃; Schlenk technique; Inert atmosphere;

Reference： [1]Li, ShengJian; Dieter, R.Karl [Journal of Organic Chemistry, 2003, vol. 68, # 3, p. 969 - 973]
[2]Miura, Masanori; Koike, Takanori; Ishihara, Tsukasa; Hirayama, Fukushi; Sakamoto, Shuichi; Okada, Minoru; Ohta, Mitsuaki; Tsukamoto, Shin-Ichi [Synthetic Communications, 2006, vol. 36, # 24, p. 3809 - 3820]
[3]Goossen, Lukas J.; Linder, Christophe; Rodriguez, Nuria; Lange, Paul P. [Chemistry - A European Journal, 2009, vol. 15, # 37, p. 9336 - 9349] Goossen, Lukas J.; Lange, Paul P.; Rodriguez, Nuria; Linder, Christophe [Chemistry - A European Journal, 2010, vol. 16, # 13, p. 3906 - 3909]
[4]Picado, Alfredo; Li, ShengJian; Dieter, R. Karl [Journal of Organic Chemistry, 2016, vol. 81, # 4, p. 1391 - 1400]
[5]Zhang, Shuo; Yang, Lei; Fu, Jianbin; Tan, Qihang; Liu, Kuan; Huang, Tianzeng; Li, Chunya; Liu, Long; Chen, Tieqiao [Organic and Biomolecular Chemistry, 2023, vol. 21, # 21, p. 4398 - 4403]

24
[ 106-96-7 ]
[ 118-61-6 ]
[ 528599-00-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In tetrahydrofuran
	With 18-crown-6 ether; potassium carbonate In N,N-dimethyl-formamide; toluene at 20℃; for 20h;
	With potassium carbonate In propan-2-one Reflux;	To solution of ethyl salicylate 4 (6.7 g, 40 mmol) in ace- tone (60 mL), anhydrous potassium carbonate (200 mmol) and propargyl bromide (60 mmol) were added under stirring, then kept reaction under refluxing and monitored with TLC (petroleum ether/ethyl acetate = 9/1). Quenching with 100 mL cold water after the reaction completed, the mixture was extracted with ethyl acetate (50 mL ×3) for three times. The organic solution then was washed sequentially with water and saturated saline, dried with anhydrous Na 2 SO 4 and concentrated in vacuum to give crude product. This crude product was purified by silica gel col- umn chromatography (petroleum ether/ethyl acetate = 9/1) to pro- vide intermediate compound 5 . To a dried Schlenk tube under N 2 , 1, 4-dioxane (15 mL), Cu (Ac) 2 (0.1 g, 0.5 mmol) and 1, 10- Phenanthroline monohydrate (0.1 g, 0.5 mmol) the intermediate compounds 3a-f (10 mmol) was added, triethylamine (1 mL) sub- sequently added under stirring in 5 min at room temperature, then the intermediate compound 5 (0.3 g, 11 mmol) was added. The re- action was kept on refluxing and monitored with TLC. Quenched with 100 mL cold water after reaction finishing, the reaction so- lution was extracted with ethyl acetate (50 mL ×3) for three times. After washing with water and saturated brine, drying with anhydrous Na 2 SO 4 , concentrating under vacuum, the organic ex- tract provided a crude product. Intermediate compounds 6a-f was obtained by purifying this crude product (petroleum ether/ethyl acetate = 20/3) by silica gel column flash chromatography. To in- termediate compounds 6a-f (5 mmol) in the mixture of EtOH (40 mL), DCM (5 mL) and H 2 O (5 mL) sodium hydroxide (0.4 g, 10 mmol) was added under stirring at room temperature. After 12 h, the reaction system was acidified with aqueous HCl solution (1M) to p H = 3, then water (70 mL) was added, subsequently ex- tracted with ethyl acetate (50 mL ×3) for three times. The ethyl acetate solution washed with saturated saline, dried with anhy- drous Na 2 SO 4 and concentrated to give intermediates compounds 7a-f .

Stage #1: 2-hydroxy-benzoic acid ethyl ester With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: propargyl bromide In N,N-dimethyl-formamide at 100℃; for 2h;

2.2.1. Step (i) (General procedure for the synthesis of 2a-2c) General procedure: To the solution of compound 1a-1c (1 eq.) in DMF at 0 °C fol- lowed by K 2 CO 3 (2 eq.) and stirred for 30 min. at room tempera- ture. Then added Proggyl bromide (1.5 eq.) dropwise and heated the reaction mixture at 100 °C for two h. The progress of the reaction was monitored by TLC for the consumption of start- ing material. The reaction mixture was cool to room temperature and poured in ice-cold water, stirred for 10 min, and extracted with EtOAc. The organic layer was separated and washed with cold brine solution. The organic phase was dried over anhydrousNa 2 SO 4 , filtered, and the solvent removed under reduced pressure to afford title crude compounds ( 2a-2c ). The crude compounds were used for the following reaction without further purification. Ethyl 2-(prop2-yn-1-yloxy)benzoate ( 2a ) The reaction was done on 2 g to obtain a pale yellow liquid with a 90% yield.

Reference： [1]Lingam, V.S. Prasada Rao; Vinodkumar, Ramanatham; Mukkanti, Khagga; Thomas, Abraham; Gopalan, Balasubramanian [Tetrahedron Letters, 2008, vol. 49, # 27, p. 4260 - 4264]
[2]Rosowsky, Andre; Forsch, Ronald A.; Queener, Sherry F. [Journal of Medicinal Chemistry, 2003, vol. 46, # 9, p. 1726 - 1736]
[3]Xie, Ziyue; Liang, Zhengcheng; Huang, Yunhou; Shi, Kaichuang; Zang, Ning; Wang, Mian; Liang, Taoyuan; Wei, Wanxing [Journal of Molecular Structure, 2023, vol. 1272]
[4]Shinde, Suraj R.; Inamdar, Shaukatali N.; Shinde, Mahadev; Pawar, Chandrakant; Kushwaha, Babita; Obakachi, Vincent A.; Kajee, Afsana; Chauhan, Ruchika; Karpoormath, Rajshekhar [Journal of Molecular Structure, 2023, vol. 1273]

25
[ 118-61-6 ]
[ 69-72-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With barium dihydroxide In methanol at 80℃; for 2h;
	Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 25 °C 2: sodium hydroxide; water / ethanol / 60 °C 3: [1,2-bis-(phenylsulfinyl)ethane]palladium(II) acetate; silver trifluoromethanesulfonate; silver carbonate / tetrahydrofuran / 12 h / 70 °C / Sealed tube; Inert atmosphere
45 %Chromat.	With water; lithium hydroxide In tetrahydrofuran at 25℃; for 15h;	General Procedure for Hydrolysis of Esters General procedure: To a THF (1.0 mL) solution of ester (1.0 mmol) was added a 3.0 mol/L solution of hydroxide (LiOH, NaOH, or KOH) (1.0 mL, 3.0 mmol), and the reaction mixture was stirred at 25 ± 0.02 °C for 0.25-60 h (see Tables 1-4). The reaction was then quenched with 1.0 mol/L HCl (9.0 mL) for 3 min, and the mixture was adjusted accurately to a 250-mL volume with aqueous CH3CN (50% (v/v)). The resulting diluted solution was used for the HPLC an sis as a sample solution with TSkgel ODS-80Ts (150 × 4.6 mm) as a separation column. In the mobile phase, CH3CN/phosphate buffer (1/15 mol/L,pH 7.0) = 1 : 1 (v/v) or CH3CN/H2O (0.1% trifluoroacetic acid(TFA) (v/v)) = 1 : 1 (v/v); flow rate, 1.0 mL/min; measurement at room temperature (20-25 °C); detection wavelength,254 nm. The yield (%) was determined by utilizing the peak area ratios of the reaction mixture to that of the standard acid in the chromatogram.

Reference： [1]Anderson, Marc O.; Moser, Jamie; Sherrill, John; Guy, R. Kiplin [Synlett, 2004, # 13, p. 2391 - 2393]
[2]Begam, Hasina Mamataj; Jana, Ranjan; Manna, Kartic; Samanta, Krishanu [Organic Letters, 2020, vol. 22, # 19, p. 7443 - 7449]
[3]Hayashi, Kazuhiko; Ichimaru, Yoshimi; Sugiura, Kirara; Maeda, Azusa; Harada, Yumi; Kojima, Yuki; Nakayama, Kanae; Imai, Masanori [Chemical and Pharmaceutical Bulletin, 2021, vol. 69, # 6, p. 581 - 594]

26
[ 7335-26-4 ]
[ 118-61-6 ]

Yield	Reaction Conditions	Operation in experiment
56%	With 2-(diethylamino)ethanethiol hydrochloride; sodium t-butanolate In N,N-dimethyl-formamide for 1h; Heating;

Reference： [1]Magano, Javier; Chen, Michael H.; Clark, Jerry D.; Nussbaumer, Thomas [Journal of Organic Chemistry, 2006, vol. 71, # 18, p. 7103 - 7105]

27
[ 540-88-5 ]
[ 118-61-6 ]
[ 936182-86-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: acetic acid tert-butyl ester With n-butyllithium; N-isopropylpropan-2-amine In tetrahydrofuran at -78℃; for 1.5h; Stage #2: 2-hydroxy-benzoic acid ethyl ester In tetrahydrofuran at -78 - 20℃; Further stages.;
75%	With n-butyllithium; N-isopropylpropan-2-amine In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	1 Example 1 Example 1 tert-butyl 3-(2-hydroxyphenyl)-3-oxopropanoate (18): To a N2 purged 250 mL RBF is added 30 mL of THF and diisopropylamine (12.0 mL, 86 mmol). The solution is cooled to -78° C. and nBuLi (50 mL, 1.6 M) is added and the solution is warmed to 0° C. for 45 min. The solution is cooled to -78° C. and t-butyl acetate (7.1 mL, 53 mmol) in 12 mL THF is added dropwise over 10 minutes. After 90 min., ethyl salicylate (2.2 mL, 15 mmol) in 15 mL of THF is added. The solution is allowed to warm to RT overnight and quenched with 90 mL of aq. NH4Cl (sat.), extracted with EtOAc (2*25 mL), washed brine (40 mL), dried Na2SO4, filtered, concentrated in vacuo. Purified via column chromatography (silica gel, 10% EtOAc/hex) to give 2.65 g of pale yellow oil (75% yield). IR (film) 2980.2; 2934.9; 1733.6; 1643.7; 1146.6; 757.0 cm-1; 1H NMR (500 MHz, CDCl3) δ 11.93 (s, 1H); 7.68 (d, J=7.9 Hz, 1H); 7.51 (t, J=7.3, 1H); 7.01 (d, J=8.2 Hz, 1H); 6.93 (t, J=7.3 Hz, 1H); 3.93 (s, 2H); 1.47 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 198.7, 165.8, 162.3, 136.6, 130.3, 118.8, 118.7, 118.3, 82.1, 46.9, 27.6; LRMS (electrospray): Mass calculated for C13H16O4, [M]+, 236.10. Found, [M+23]+259.5.
73%	Stage #1: acetic acid tert-butyl ester With n-butyllithium; N-isopropylpropan-2-amine In tetrahydrofuran; hexane at -78℃; for 1.66667h; Inert atmosphere; Stage #2: 2-hydroxy-benzoic acid ethyl ester In tetrahydrofuran; hexane at 20℃; Inert atmosphere;	3.8. Tert-Butyl 3-(2-hydroxyphenyl)-3-oxopropanoate (16) A solution of diisopropylamine (5.0 mL, 36.0 mmol) in THF (12.5 mL) under nitrogenatmosphere was cooled to 78 C and n-BuLi (21.0 mL, 1.6 M in hexane) was added. Thecooling was removed, and the solution was left warming to 0 C. Then it was cooledagain to 78 C and a solution of t-butyl acetate (2.95 mL, 22.0 mmol) in THF (5.0 mL)was added dropwise over 10 min. After 90 min of stirring, a solution of ethyl salicylate(0.92 mL, 6.3 mmol) in THF (6.5 mL) was added and the reaction mixture was warmedto room temperature and stirred overnight. The mixture was quenched with 40 mL of aq.NH4Cl (sat.) and extracted with EtOAc (2 x 25 mL). The collected organic phases werewashed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated atreduced pressure. The crude product was purified using column chromatography (silicagel, EP/AcOEt 9:1) providing pure 16 [49] as a pale-yellow oil (1.07 g, 73% yield). 1H NMR(500 MHz, CDCl3) 1.46 (s, 9H); 3.92 (s, 2H); 6.92 (t, J = 7.3 Hz, 1H); 7.00 (d, J = 8.2 Hz, 1H);7.50 (t, J = 7.3 Hz, 1H); 7.67 (d, J = 8.0 Hz, 1H); 11.92 (s, 1H). 13C NMR (125 MHz, CDCl3)27.6; 46.9; 82.1; 118.3; 118.7; 118.8; 130.3; 136.6; 162.3; 165.8; 198.7.

Reference： [1]Biddle, Margaret M.; Lin, Michael; Scheidt, Karl A. [Journal of the American Chemical Society, 2007, vol. 129, # 13, p. 3830 - 3831]
[2]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - US2009/259055, 2009, A1 Location in patent: Page/Page column 14
[3]Summa, Assunta; Scafato, Patrizia; Belviso, Sandra; Monaco, Guglielmo; Zanasi, Riccardo; Longhi, Giovanna; Abbate, Sergio; Superchi, Stefano [Molecules, 2022, vol. 27, # 16]

28
[ 99337-98-1 ]
[ 118-61-6 ]
[ 948304-25-4 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3825 - 3840

29
[ 118-61-6 ]
[ 2200-81-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 77 percent / K₂CO₃ / dimethylformamide / 3 h / 70 °C 2: 89 percent / aq. NaOH / dioxane / 1 h / Heating
	Multi-step reaction with 2 steps 1.1: potassium carbonate / butanone / 48 h / Heating / reflux 2.1: sodium hydroxide; water / ethanol / 2 h / 50 °C 2.2: 5 °C / pH 2

Reference： [1]Chung, De Michael; Nowick, James S. [Journal of the American Chemical Society, 2004, vol. 126, # 10, p. 3062 - 3063]
[2]Current Patent Assignee: NOVO NORDISK A/S - WO2008/116141, 2008, A1

30
[ 118-61-6 ]
[ 2100-31-4 ]

Reference： [1]Journal of the Chemical Society,1944,p. 19

31
[ 118-61-6 ]
[ 7120-43-6 ]

Reference： [1]Gazzetta Chimica Italiana,1899,vol. 29 I,p. 342,345

32
[ 4457-67-4 ]
[ 118-61-6 ]
[ 179993-32-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; potassium carbonate; In acetonitrile;	b) 2-(4-Methoxybutoxy)-benzoic acid ethyl ester A solution of <strong>[4457-67-4]4-methoxybutyl bromide</strong> (4.5 g) in acetonitrile (15 ml) is added dropwise under reflux to a mixture of salicylic acid ethyl ester (2.63 ml), powdered potassium carbonate (3.10 g) and potassium iodide (10 mg) in acetonitrile (50 ml), and the reaction mixture is then stirred overnight. After cooling, filtration is carried out, the filtrate is concentrated and the residue is added under a high vacuum. The title compound (4.4 g), Rf (C)=0.28, is obtained in the form of a pale-yellow oil.
	With potassium carbonate; potassium iodide; In acetonitrile;Heating / reflux;	A solution of <strong>[4457-67-4]4-methoxybutyl bromide</strong> (4.5 g) in acetonitrile (15 ml) is added dropwise under reflux to a mixture of salicylic acid ethyl ester (2.63 ml), powdered potassium carbonate (3.10 [G)] and potassium iodide (10 mg) in acetonitrile (50 ml), and the reaction mixture is then stirred overnight. After cooling, filtration is carried out, the filtrate is concentrated and the residue is added under a high vacuum. The title compound (4.4 g), Rf (C) =0.28, is obtained in the form of a pale-yellow oil.

Reference： [1]Patent: US5641778,1997,A
[2]Patent: WO2003/103652,2003,A1 .Location in patent: Page 161

33
[ 35654-56-9 ]
[ 118-61-6 ]
[ 666729-96-0 ]

Yield	Reaction Conditions	Operation in experiment
56%	With dmap In 1,2-dichloro-benzene at 120℃;	Compound 80: Ethyl 2-[(6,7-dimethoxy-4-quinolyl)oxy]benzoate Compound 80: Ethyl 2-[(6,7-dimethoxy-4-quinolyl)oxy]benzoate; 4-Chloro-6,7-dimethoxyquinoline (100 mg), ethyl salicylate (336 mg), and 4-dimethylaminopyridine (244 mg) were suspended in o-dichlorobenzene (1 ml), and the suspension was stirred at 120°C overnight. The reaction solution was cooled to room temperature, and the solvent was removed by distillation under the reduced pressure. Water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give the title compound (100 mg, yield 56%). 1H-NMR (CDCl3, 400 MHz): δ 0.87 (t, 3H), 4.06 (m, 8H), 6.28 (d, J = 5.4 Hz, 1H), 7.23 - 7.42 (m, 3H), 7.64 (m, 2H), 8.07 (dd, J = 7.8 Hz, 1.7 Hz, 1H), 8.45 (d, J = 5.4 Hz, 1H) Mass spectrometric value (ESI-MS, m/z): 354 (M+1)+

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO LTD - EP1548008, 2005, A1 Location in patent: Page/Page column 81-82

34
[ 321538-19-6 ]
[ 118-61-6 ]
ethyl 2-(3-phenyl-5-chloro-1-methyl-1H-pyrazol-4-ylmethoxy)-benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With caesium carbonate; In acetonitrile; for 4.0h;	The mixture of 3-phenyl-5-chloro-4-chloromethyl-1-methyl-lH-pyrazole (8. 44 g, 0.035 mol), ethyl 2-hydroxybenzoate (5. 82, 0.035 mol), cesium carbonate (11.40 g, 0.035 mol) and acetonitrile (200 ml) is heated under stirring for 4 hours. The reaction mixture is evaporated in vacuum, to the residue water (300 ml) is added and extracted with chloroform (3 x 150 ml) and evaporated in vacuum. The organic phase is washed with water (3 x 100 ml), dried over sodium sulphate and the solvent is removed in vacuum. The residual orange-coloured oil crystallises on addition of ethanol (10 ml). The crystals are collected, washed with ethanol (2 x 5 ml) to obtain 5.48 g (42 %) of white crystalline ester, m. p.: 77 C. NMR, 6H (200 MHz, DMSO-d6) : 1.10 (t, J=7.1 Hz, 3H), 3. 89 (s, 3H, 1-CH3), 4.12 (q, J=7, 1 Hz, 2H), 4.97 (s, 2H, CH20), 7.03-7. 10 (m, 1H), 7.29-7. 75 (m, 8H).

Reference： [1]Patent: WO2005/60959,2005,A1 .Location in patent: Page/Page column 30

35
[ 1077-28-7 ]
[ 118-61-6 ]
[ 1028262-79-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h;	6 A 1N solution of dicyclohexylcarbodiimide (DCC)(1,100 g, 5,3 mmol) in dichloromethane was added to a solution of ethyl salicylate (645 mg, 3,88 mmol), lipoicacid (1,050 g, 5 mmol) and dimethylaminopyridine (DMAP)(20,5 mg) in 50 ml of anhydrous dichloromethane.The mixture was stirred at room temperature for 3 hours under nitrogen. At the end of the reaction, the resulting mixture was filtered and the solution was evaporated and the residue chromatographed on silica gel eluting with dichloromethane/cyclohexane (1/1) .The resulting product was a viscous yellow oil with anyield >90%.

Reference： [1]Current Patent Assignee: C T G PHARMA - WO2006/66894, 2006, A1 Location in patent: Page/Page column 17

36
[ 3153-32-0 ]
[ 118-61-6 ]
ethyl 2-(3-tert-butoxycarbonylpropoxy)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With caesium carbonate In <i>N</i>-methyl-acetamide; hexane	7.f (Compound 29) (f) A mixture comprising ethyl salicylate (3.14 g, 18.9 mmol) and cesium carbonate (6.2 g, 18.9 mmol), dimethylformamide (25 mL) and tert-butyl 4-chlorobutyrate (4.08 g, 22.8 mmol) was heated at 70° C. and stirred for 12 hours. The mixture was partitioned between ethyl ether (100 mL) and water and the organic layer was separated and washed with additional water (3*) and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a colorless oil. The residue was purified by silica gel flash chromatography using pure hexane to (10:1) hexane:ethyl acetate to provide ethyl 2-(3-tert-butoxycarbonylpropoxy)benzoate (3.6 g, 62% yield) as a colorless oil; 1H NMR (300 MHz, CDCl3): 7.80 (d, 1H), 7.49 (tr, 1H), 7.00 (m, 2H), 4.40 (q, 2H), 4.10 (tr, 2H), 2.50 (tr, 2H), 2.10 (m, 2H), 1.45 (s, 9H), 1.40 (tr, 3H).

Reference： [1]Current Patent Assignee: QUEST DIAGNOSTICS INC - US2001/53779, 2001, A1

37
[ 506-96-7 ]
[ 507-20-0 ]
[ 118-61-6 ]
[ 187273-02-5 ]

Yield	Reaction Conditions	Operation in experiment
45%	With hydrogenchloride In dichloromethane	S.21 Synthesis of 5-t-butyl-3-ethoxycarbonyl-2-hydroxyacetophenone Synthesis Example 21 Synthesis of 5-t-butyl-3-ethoxycarbonyl-2-hydroxyacetophenone Ethyl salicylate (10 g, 60 mmol) was dissolved in 50 ml of dichloromethane, followed by the addition of 11.75 g (88 mmol) of anhydrous aluminum chloride. Then, 5.6 g (60 mmol) of t-butyl chloride were dropped. After the resultant mixture was stirred at room temperature for 3 hours, 14.8 g (120 mmol) of acetyl bromide were added slowly. Subsequent to overnight stirring, the reaction mixture was poured into ice water which contained 3 M hydrochloric acid. The resulting mixture was extracted with ethyl acetate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (ethyl acetate/petroleum ether=1/20), whereby 7.20 g of the title compound were obtained (yield: 45%). Melting point: 63.5-65.3° C. 1 H-NMR(CDCl3)δ(ppm): 1.24(9H,s,C(CH3)3), 1.36(3H,t,J=7.1 Hz,CO2 CH2 CH3), 2.62(3H,s,COCH3), 4.36(2H,q,J=7.1 Hz,Co2 CH2 CH3), 7.93(1H,d,J=2.7 Hz,H4), 7.98(1H,d,J=2.7 Hz,H6).

Reference： [1]Current Patent Assignee: KOWA COMPANY, LTD. - US6046212, 2000, A

38
[ CAS Unavailable ]
[ 118-61-6 ]
[ 16697-77-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With acetic acid In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; toluene	1.6 (6) (6) Synthesis of 2'-hydroxy-2-(methylsulfinyl) acetophenone: To 28.6 g (60% oily, 3.4 equivalent) of sodium hydride, 447 ml of toluene and 192 ml of N,N-dimethysulfoxide (hereinafter "DMSO") were added in an atmosphere of argon, and the mixture obtained was heated at 80° C. for 1 hour. The reaction solution was cooled to 35° C., and a toluene 220 ml solution of 31.4 g (188.9 mmols) of ethyl salicylate was dropwise added thereto, followed by heating at 80° C. for 2 hours. The resultant reaction solution was cooled to room temperature, and thereafter the toluene was evaporated off. The residue thus obtained was poured into 1,000 ml of ice water, and acetic acid was added to adjust the pH to 4. Crystals thus deposited were collected by filtration, and then washed with water and hexane, followed by natural drying for 1 hour. To 38.5 g of the crude-purified product thus obtained, 350 ml of ethanol was added to effect dissolution with heating using a 90° C. hot water bath, which was then left overnight at room temperature. Crystals thus deposited were collected by filtration, and then washed with ethanol, followed by vacuum drying (60° C./5 torr) for 2 hours to obtain 32.1 g of 2'-hydroxy-2-(methylsulfinyl)acetophenone (yield: 85%). 1 H-NMR Spectrum [δ(ppm)]: 2.78(s, 3H), 4.36(q, 2H, J=15.3 Hz), 6.97(t, 1H, J=7.8 Hz), 7.00(d, 1H, J=7.8 Hz), 7.55(t, 1H, J=1.5 Hz, 8.0 Hz), 7.76(dd, 1H, J=1.5 Hz, 8.0 Hz), 11.80(s, 1H)

Reference： [1]Current Patent Assignee: RESONAC HOLDINGS CORPORATION - US6051722, 2000, A

39
[ 119-26-6 ]
[ 118-61-6 ]
[ 79616-09-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	In ethanol at 20℃; for 2h;	3 A mixture of ethyl salicylate (0.1M), 2,4-dinitrophenylhydrazine (0.1M) in ethanol (150 mL) was stirred at room temperature for 2 hours. The separated orange solid was filtered, washed with ethanol and dried. Recrystallization from ethanol furnished pure hydrazide in 94% yield.

Reference： [1]Current Patent Assignee: C2C TECHNOLOGIES LLC - US2006/222601, 2006, A1 Location in patent: Page/Page column 32

40
[ 57616-74-7 ]
[ 584-08-7 ]
[ 118-61-6 ]
2-(3-morpholino-propoxy)-benzoic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	(a) To a mixture of ethyl 2-hydroxybenzoate (2.4 ml, 16.38 mmol), K2 CO3 (4.98 g), and DMF (30 ml) was added <strong>[57616-74-7]N-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong> (3.93 g). The mixture was stirred at room temperature for 30 minutes, then was warmed on a steam bath overnight. The reaction mixture was cooled, filtered and stripped to afford a liquid which was partitioned between EtOAc (350 ml) and water. The organic layer was separated, washed with water (2*200 ml), dried over MgSO4 and stripped to afford ethyl 2-[3-(4-morpholinyl)propoxy]benzoate.

Reference： [1]Patent: US5736548,1998,A

41
[ 100-16-3 ]
[ 118-61-6 ]
[ 911213-08-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	In ethanol at 20℃; for 2h;	5 A mixture of ethyl salicylate (0.1M), 4-nitrophenylhydrazine (0.1M) in ethanol (150 mL) was stirred at room temperature for 2 hours. The separated yellow solid was filtered, washed with ethanol and dried. Recrystallization from ethanol furnished pure hydrazide in 89% yield.

Reference： [1]Current Patent Assignee: C2C TECHNOLOGIES LLC - US2006/222601, 2006, A1 Location in patent: Page/Page column 32

42
[ 5470-11-1 ]
[ 118-61-6 ]
[ 89-73-6 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; sodium hydroxide;	(1) Hydroxylammonium hydrochloride (15 g) was dissolved in 10% aqueous sodium hydroxide solution (220 mL), and a solution of ethyl salicylate (24 g) in 1,4-dioxane (70 mL) was gradually added, and the mixture was stirred at room temperature for 5 hr. The reaction mixture was concentrated until the amount thereof became almost the half, and acidified with conc. hydrochloric acid. The precipitated solid was collected by filtration, which was then recrystallized from methanol to give salicylhydroxamic acid (12 g) as white crystals.

Reference： [1]Patent: EP1308439,2003,A1

43
[ 105-36-2 ]
[ 118-61-6 ]
[ 56424-77-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium carbonate In acetone at 60℃; for 3h;
96%	With potassium carbonate In acetone at 60℃; for 3h;	Intermediate 4: Ethyl-2-(2-ethoxy-2-oxoethoxy)benzoate Intermediate 4: Ethyl-2-(2-ethoxy-2-oxoethoxy)benzoate To a solution of ethyl-2-hydroxybenzoate (884 μ, 6.02 mmol) in acetone (11 mL) was added potassium carbonate (2.50 g, 18.1 mmol) and ethyl bromoacetate (667 μ, 6.02 mmol). The reaction mixture was stirred at 60 °C for 3 h. The white solid was removed by filtration and the filtrate concentrated under reduced pressure, yielding the desired product as an orange oil (1.46 g, yield: 96%). Vppm (400 MHz, CDC13) 7.83 (IH), 7.45 (IH), 7.06 (IH), 6.90 (IH), 4.71 (2H), 4.38 (2H), 4.28 (2H), 1.40 (3H), 1.30 (3H).
96%	With potassium carbonate In acetone at 60℃; for 3h;

With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 20℃; for 24h;

Reference： [1]Rackham, Mark D.; Brannigan, James A.; Moss, David K.; Yu, Zhiyong; Wilkinson, Anthony J.; Holder, Anthony A.; Tate, Edward W.; Leatherbarrow, Robin J. [Journal of Medicinal Chemistry, 2013, vol. 56, # 1, p. 371 - 375]
[2]Current Patent Assignee: IP GROUP PLC - WO2013/83991, 2013, A1 Location in patent: Page/Page column 67
[3]Zhao, Long; Huang, Guanxin; Guo, Beibei; Xu, Lijun; Chen, Jie; Cao, Weiguo; Zhao, Gang; Wu, Xiaoyu [Organic Letters, 2014, vol. 16, # 21, p. 5584 - 5587]
[4]Hadj-esfandiari, Narges; Navidpour, Latifeh; Shadnia, Hooman; Amini, Mohsen; Samadi, Nasrin; Faramarzi, Mohammad Ali; Shafiee, Abbas [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6354 - 6363]

44
[ 28237-14-1 ]
[ 118-61-6 ]
[ 1065043-49-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With trifluorormethanesulfonic acid In chloroform at 20℃; for 4h;

Reference： [1]Sai, Kiran Kumar Solingapuram; Tokarz, Matthew J.; Malunchuk, Andrew P.; Zheng, Chong; Gilbert, Thomas M.; Klumpp, Douglas A. [Journal of the American Chemical Society, 2008, vol. 130, # 44, p. 14388 - 14389]

45
[ 4530-18-1 ]
[ 118-61-6 ]
ethyl 2-(2-(tert-butoxycarbonylamino)-3-phenylpropanoyloxy)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 3h;	Example 27; Preparation of ethyl 2-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamido-3-phenylpropanoyloxy)benzoate (22); To a solution of ethyl 2-hydroxybenzoate (0.5 g, 3.0 mmol) in CH2Cl2 (8 mL) was added 2-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (0.8 g, 3.0 mmol), EDCl (0.63 g, 3.3 mmol) and dimethylaminopyridine (0.037 g, 0.3 mmol). The reaction was stirred (RT, 3 h) and then partitioned between CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 and the combined organic extracts were dried over MgSO4. The crude material was purified by silica chromatography (0-10% MeOH/CH2Cl2) to afford 1.2 g of ethyl 2-(2-(tert-butoxycarbonylamino)-3-phenylpropanoyloxy)benzoate. Mass calculated for C235H27NO6=413.46; found: [M+Na]+=437.1.

Reference： [1]Patent: US2010/41748,2010,A1 .Location in patent: Page/Page column 127-128

46
[ 1892612-91-7 ]
[ 118-61-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
67%	With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran; acetonitrile at -10 - 20℃;	15 To a solution of 2-docosa-4,7,10,13,16,19-hexaenamido-4-methylpentanoic acid (50 mg, 0.11 mmol) and ethyl 2-hydroxybenzoate (19 mg, 0.11 mmol) in CH3CN/THF (1:1, 0.5 mL) at -10° C. was added DCC (12 mg, 0.11 mmol) and DMAP (1 mg). The mixture was stirred (RT, 16 h), filtered and concentrated under reduced pressure. The crude product was purified by silica chromatography (EtOAc-PE, 0-20%) to afford ethyl 2-(2-docosa-4,7,10,13,16,19-hexaenamido-4-methylpentanoyloxy)benzoate (40 mg, 67%) as colorless oil. Mass calculated for C37H51NO5=589.80; found: [M+H]+=590.4.

Reference： [1]Current Patent Assignee: ASTRIA THERAPEUTICS INC - US2010/41748, 2010, A1 Location in patent: Page/Page column 118

47
[ 1003572-77-7 ]
[ 64-19-7 ]
[ 118-61-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
85.9%	Stage #1: 3-(diethyl-amino)propionyl chloride hydrochloride; 2-hydroxy-benzoic acid ethyl ester With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	8 8. Preparation of ethyl 3-N, N-dimethylaminopropionyl salicylateAcOH[47] 16.6 g (0.1 mol) of ethyl salicylate was dissolved in 100 ml of chloroform (100 ml).The mixture was cooled to 0°C. 21 ml (0.2 mol) of triethylamine and 17.2 g (0.1 mol) of 3-N, N-dimethylaminopropionyl chloride hydrochloride were added into the reaction mixture. The mixture is stirred for 3 h at RT. The solid is removed by filtration. Acetic acid (6 g) was added into the reaction mixture with stirring. Hexane (200 ml) was added. The solid product was collected by filtration. After drying, it yielded 28 g of the desired product (85.9%). Hygroscopic product; Solubility in water: 400 mg/ml; Elementary analysis: C H NO ; MW: 325.36. Calculated % C: 59.06; H: 7.13; N: 4.31; O: 29.50; Found % C: 59.03; H: 7.15; N: 4.30; O: 29.52. 1H-NMR (400 MHz, CDCl3): δ: 1.31 (t, 3H), 2.20 (s, 3H), 2.68 (t, 2H); 2.92 (m, 4H), 3.50 (m, 2H), 4.30 (m, 2H), 6.8 (b, IH), 7.18 (m, 2H), 7.44 (m, IH), 7.92 (m, IH).

Reference： [1]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - WO2008/12603, 2008, A1 Location in patent: Page/Page column 18

48
[ 112-92-5 ]
[ 118-61-6 ]
[ 14971-14-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With iron(III)-acetylacetonate In n-heptane at 105℃; for 35h; Inert atmosphere;	Representative procedure for transesterification reactions catalyzed by Fe(acac)3 in the absence of Na2CO3 General procedure: To a dry 25 mL, bottomed flask equipped with a Dean-Stark trap containing a plug of 4Å molecular sieves (pellets) and topped with a reflux condenser was added of Fe(acac)3 ( 36 mg, 0.10 mmol, 5 mol%) and a solution of methyl bezoate (272 mg, 256 .L, 2.0 mmol), benzyl alcohol (216 mg, 208 .L, 2.0 mmol) and triphenyl methane (488 mg, 2 mmol, as internal standard) in heptane (20 mL). The mixture was heated to reflux (105 ° C) for an indicated time periods. After completion of the reaction as monitored by TLC, 1H NMR and GC, the reaction mixture was cooled to room temperature and the solvent was evaporated. The crude product was purified by column chromatography on silica gel to afforded benzyl benzoate 403 mg, 95% yield. The product obtained was characterized by 1H, 13C NMR, ESI-MS or GC-MS spectroscopic methods. The conversions of the products determined by GC are based on triphenyl methane as an internal standard and are response-corrected based on authentic samples.

Reference： [1]Weng, Shiue-Shien; Ke, Chih-Shueh; Chen, Fong-Kuang; Lyu, You-Fu; Lin, Guan-Ying [Tetrahedron, 2011, vol. 67, # 9, p. 1640 - 1648]

49
[ 118-61-6 ]
[ 15125-84-5 ]

Reference： [1]European Journal of Organic Chemistry,2017,vol. 2017,p. 3234 - 3239
[2]Organic and Biomolecular Chemistry,2012,vol. 10,p. 5230 - 5237

50
[ 194222-05-4 ]
[ 118-61-6 ]
[ 1307254-73-4 ]

Yield	Reaction Conditions	Operation in experiment
	With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 20℃;	To a mixture of ethyl salicylate (2.8 mL), Compound I (3.46 g), triphenylphosphine (4.9 g) and toluene (78 mL) was added diisopropyl azodicarboxylate (3.7 mL), and the mixture was stirred at room temperature overnight. The reaction solution was washed successively with 1M aqueous sodium hydroxide solution, 1M hydrochloric acid and a saturated brine. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=6/1) to give Compound II (5.17 g).

Reference： [1]Patent: US2012/225876,2012,A1 .Location in patent: Page/Page column 38-39

51
[ 100-51-6 ]
[ 118-61-6 ]
[ 110519-56-7 ]

Yield	Reaction Conditions	Operation in experiment
51%	With tert.-butylhydroperoxide; copper diacetate In water; dimethyl sulfoxide at 80℃; for 20h; Sealed tube;	10 Typical procedure for the esterification of 2-carbonyl substituted phenols General procedure: To an oven-dried sealed tube charged with 2-hydroxyacetophenone (1a) (40.8mg, 0.3mmol, 1.0equiv), Cu(OAc)2 (2.7mg, 0.015mmol, 5mol%), and TBHP (70% in water) (0.16mL, 1.2mmol, 4.0equiv) in DMSO (1mL, 0.3M) was added benzyl alcohol (2a) (65.4mg, 0.6mmol, 2equiv). The reaction mixture was allowed to stir at 80°C for 20h. After cooling at room temperature, the reaction mixture was evaporated onto silica gel. Purification of the product by column chromatography (SiO2: n-hexanes/EtOAc=40:1) provided 3a (50.5mg) in 70% yield 4.2.10 Ethyl 2-(benzoyloxy)benzoate (3j) Colorless sticky solid; Rf=0.45 (n-hexanes/EtOAc=6:1); 1H NMR (700 MHz, CDCl3) δ 8.21 (d, J=8.0 Hz, 2H), 8.07 (d, J=7.9 Hz, 1H), 7.63-7.56 (m, 2H), 7.50 (t, J=7.9 Hz, 2H), 7.34 (t, J=8.8 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 4.19 (q, J=7.1 Hz, 2H), 1.07 (t, J=7.0 Hz, 3H); 13C NMR (175 MHz, CDCl3) δ 165.2, 164.7, 150.5, 133.6, 133.5, 131.9, 130.2, 129.4, 128.5, 126.0, 123.9, 123.8, 61.1, 13.8; IR (KBr) ν 2982, 1742, 1720, 1606, 1451, 1295, 1266, 1204, 1125, 1061, 1023 cm-1; HRMS (EI) calcd for C16H14O4 [M]+ 270.0892, found 270.0892.

Reference： [1]Sharma, Satyasheel; Park, Jihye; Kim, Mirim; Kwak, Jong Hwan; Jung, Young Hoon; Kim, In Su [Tetrahedron, 2013, vol. 69, # 45, p. 9391 - 9397]

52
[ 303224-88-6 ]
[ 118-61-6 ]
[ 1552276-12-6 ]

Yield	Reaction Conditions	Operation in experiment
68%	With potassium carbonate In acetonitrile at 90℃; for 5h;	3 2.2.3. Synthesis of ethyl 2-((4-chloroquinolin-2-yl)methoxy)benzoate (5a) Intermediate 1 (10 mmol, 2.11 g) was dissolved in 50 mL CH3CN. After the addition of ethyl 2-hydroxybenzoate (11 mmol, 1.83 g), followed by K2CO3 (10 mmol, 1.38 g), the mixture was heated at 90 °C for 5 h. The solution was poured into water, and filtered to give a white solid 5a (2.32 g, 68%). 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 9.2 Hz, 1H), 8.10 (d, J = 10.0 Hz, 2H), 7.88 (dd, J = 7.8, 1.8 Hz, 1H), 7.82 - 7.78 (m, 1H), 7.67 - 7.63 (m, 1H), 7.46 (m, 1H), 7.05 (dd, J = 16.0, 8.0 Hz, 2H), 5.44 (s, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 181.1, 166.3, 157.8 157.5, 148.2, 143.7, 133.5, 132.0, 130.6, 129.2, 127.4, 125.9, 124.2, 121.11, 121.05, 119.4, 113.5, 71.2, 61.1, 14.4; ESI-HRMS m/z: calcd for C19H16NO3Cl [M + Na]+ 364.0711, found 364.0703.

Reference： [1]Liu, Jinggong; Liu, Weilin; Ge, Hu; Gao, Jinbo; He, Qingqing; Su, Lijuan; Xu, Jun; Gu, Lian-Quan; Huang, Zhi-Shu; Li, Ding [Biochimica et Biophysica Acta - General Subjects, 2014, vol. 1840, # 3, p. 1051 - 1062]

53
[ 579-75-9 ]
[ 118-61-6 ]
[ 7335-26-4 ]
[ 69-72-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 2-Methoxybenzoic acid With potassium carbonate In N,N-dimethyl acetamide at 110℃; for 0.5h; Stage #2: 2-hydroxy-benzoic acid ethyl ester at 130℃; for 24h;	Methyl 2-Methoxybenzoate (3a); Typical Procedure General procedure: A mixture of 2-methoxybenzoic acid (3.8 g, 25 mmol) and K2CO3 (2.07 g, 15 mmol) in DMA (50 mL) was stirred at 110 °C for 0.5 h. Methyl salicylate (5.70 g, 37.5 mmol) was added and the resulting mixture was stirred for 24 h. The solvent was then removed in vacuo. After cooling to r.t., K2CO3 (2.42 g, 17.5 mmol) and water (50mL) were added to hydrolyze the excess methyl salicylate. The resulting mixture was heated at 60 °C until methyl salicylate disappeared on TLC. Then, the solution was extracted with EtOAc (3 ×20 mL). The organic layer was washed with water, sat. aq NaCl solution,and dried (anhyd MgSO4). Evaporation of solvent in vacuoafforded methyl 2-methoxybenzoate (3.82 g, 92%). More than 90% of salicylic acid was recovered as a white precipitate by acidifying the aqueous phase with 1 M HCl.

Reference： [1]Chen, Si; Jia, Lei; Li, Xiaonan; Luo, Meiming [Synthesis, 2014, vol. 46, # 2, p. 263 - 268]

54
[ 118-61-6 ]
[ 20237-92-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 2 h / 170 °C 2: thionyl chloride / dichloromethane / 0 °C

Reference： [1]Schachner, Jörg A.; Terfassa, Belina; Peschel, Lydia M.; Zwettler, Niklas; Belaj, Ferdinand; Cias, Pawel; Gescheidt, Georg; Mösch-Zanetti, Nadia C. [Inorganic Chemistry, 2014, vol. 53, # 24, p. 12918 - 12928]

55
[ 69-72-7 ]
[ 554-70-1 ]
[ 118-61-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	With 1,3-diazido-propane In neat (no solvent) at 20℃; for 0.333333h;	General procedure forthe synthesis of alkyl esters from trialkylphosphite (3a-v) General procedure: To a mixture oftrimethylphosphite/triethylphosphite (1.0mmol) and carboxylic acid (1.0mmol),1,3-diazidopropane (0.5mmol) was added slowly in a drop wise manner (to avoidaccumulation of azide) and the mixture was stirred at room temperature for10-20 minutes. (Caution As azides arepotentially explosive, all the reactions should be carried out behind a blastshield with personal protective equipment. In particular, the sequence of addition of thereactants should be strictly followed to avoid the accumulation of organicazides. This has been achieved in thepresent investigation by the slow drop wise addition of the bis azide to thereaction mixture containing trialkylphosphite during which the azide group isinstantaneously converted to iminophosphorane and hence no difficulty wasencountered). After the completion ofthe reaction (as monitored by TLC), the mixture was poured onto crushedice. Then the reaction mixture wasextracted with dichloromethane and the organic layer was dried over anhydrousNa2SO4. Thesolvent was removed and the residue was purified by column chromatography usingsilica gel as the adsorbent and petroleum ether: ethyl acetate (98:2) as themobile phase to afford the corresponding carboxylic esters (3a-v) as colourless oily liquids. Yield (71-80%)

Reference： [1]Dinesh, Murugan; Archana, Sivasubramaniyan; Ranganathan, Raja; Sathishkumar, Murugan; Ponnuswamy, Alagusundaram [Tetrahedron Letters, 2015, vol. 56, # 50, p. 6975 - 6979]

56
[ 627-63-4 ]
[ 118-61-6 ]
[ 1588866-69-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 40℃; for 48h; Inert atmosphere;	Synthesis of bis-(2-(ethoxycarbonyl)phenyl) fumarate (40) Ethyl salicylate 39a (6.5g, 39.0 mmol, 5.7 mL) was dissolved in anhydrous CH2CI2 (100 mL) under nitrogen and cooled to 0 °C. Diisopropylethylamine (DIPEA, 4.8g, 6.5 mL, 37.2 mmol) was then added in one batch and fumaryl chloride (2.0 mL, 18.6 mmol) was then added dropwise. Following full addition, the reaction was then allowed to warm to ambient, and stirred for 24 hours, then warmed to 40 °C and stirred for an additional 24 hours. The reaction was monitored by TLC (4:1 hexanes: ethyl acetate) and once the reaction ceased to progress further, the reaction mixture was quenched by the addition of water (30 mL) and saturated ammonium chloride (30 mL). The reaction mixture was then further diluted with CH2CI2, the phases separated, and the combined organic phases, washed sequentially with saturated sodium bicarbonate and brine before drying with magnesium sulfate, filtration through a cotton plug, and concentration under reduced pressure. Column chromatography of the resulting purple solid provided the title compound as white crystals (7.6 g) in 98 % yield. Colourless crystals; Rf = 0.4 (4:1 hexanes: ethyl acetate); 1H NMR (600 MHz, CDCb): 5ppm 8.08 (dd, J = 7.84, 1 .65 Hz, 2H), 7.61 (ddd, J = 7.92, 7.81 , 1 .71 Hz, 2H), 7.37 (ddd, J = 7.73, 7.72, 1 .09 Hz, 2H), 7.31 (s, 2H), 7.18 (dd, J = 8.08, 0.91 Hz, 2H), 4.33 (q, J = 7.15 Hz, 4H), 1 .36 (t, J = 7.14 Hz, 6H); 13C NMR (150 MHz, CDCI3): 5ppm 164.3, 163.3, 149.9, 134.3, 133.9, 131 .9, 126.5, 123.5, 61 .3, 14.2.

Reference： [1]Current Patent Assignee: UNIVERSITY OF WESTERN ONTARIO - WO2015/168809, 2015, A1 Location in patent: Page/Page column 27

57
[ 118-61-6 ]
[ 13099-95-1 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 5584 - 5587

58
[ 17605-06-0 ]
[ 118-61-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With oxygen; copper diacetate; palladium diacetate; In dimethyl sulfoxide; at 45℃; under 760.051 Torr; for 23h;	General procedure: Methyl 2-hydroxybenzoate (2a).10 Pd(OAc)2 (11.7 mg, 0.052 mmol) and Cu(OAc)2 (19.0 mg, 0.105 mmol) were placed in a screw-top test tube, and a solution of m<strong>[17605-06-0]ethyl 3-oxohept-6-enoate</strong> (1a) (81.4 mg, 0.522 mmol) in DMSO (0.03 mL) was added at room temperature. The reaction mixture was stirred at 45 C for 16 h under one atmosphere of oxygen. After cooling to room temperature, the palladium residue was removed by filtering through Celite. The organic solvent was removed under reduced pressure. Then, the reaction was quenched by addition of saturated aqueous NaHCO3 solution. The solution was extracted three times with hexane-EtOAc (4:1 v/v). The combined organic layers were washed with saturated aqueous NaCl solution. The organic layers were dried over MgSO4, and filtered through Celite. The filtrate was concentrated to afford methyl 2-hydroxybenzoate (2a) (61.1 mg, 77%) as an oil.

Reference： [1]Tetrahedron Letters,2019,vol. 60,p. 1653 - 1657
[2]ChemCatChem,2016,vol. 8,p. 2472 - 2475

59
[ 357204-84-3 ]
[ 118-61-6 ]
[ 2015201-44-0 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 16h;	14.B Ethyl 2-(2-(2-(2-(tetrahydro-2H-pyran-2-yloxy)-ethoxy)-ethoxy)-ethoxy)benzoate (14-3A). To a solution of 14-1 (800 mg, 2.56 mmol) in DMF (10 mL) was added potassium carbonate (353 mg, 2.56 mmol) followed by ethyl 2-hydroxybenzoate 14-2A (553 mg, 3.33 mmol) and stirred at 70 °C for 16 hr. The reaction was cooled to RT and diluted with EtOAc (100 mL), washed with water (100 mL), and brine (50 mL) and dried over Na2S04, and the organic phase was concentrated under reduced pressure. Obtained crude compound was purified using silica gel chromatography (40% EtOAc in hexanes) to afford 14-4A (700 mg, 1.83 mmol, 71% yield). MS (ESI): m/z 382.73 (M+l)+.

Reference： [1]Current Patent Assignee: COCRYSTAL PHARMA, INC. - WO2016/154241, 2016, A1 Location in patent: Paragraph 511; 513

60
[ 98-79-3 ]
[ 118-61-6 ]
(S)-2-(ethoxycarbonyl)phenyl 5-oxopyrrolidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: L-Pyroglutamic acid; 2-hydroxy-benzoic acid ethyl ester With dmap In dichloromethane for 0.166667h; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 14h;	4.2.2. General procedure for the synthesis of L-pyroglutamic acid ester (2a-2k) and L-pyroglutamines (3a-3j) General procedure: To a round bottom flask with a stirring bar, L-pyroglutamic acid(10 mmol), phenol/aromatic amine (11 mmol) and DMAP (1 mmol) in dry CH2Cl2 (30 mL) was stirred for 10 min, followed by addition of DCC(11 mmol). The mixture was allowed to stir at room temperature overnight. The reaction was filtered through a coarse frit and the filtrate diluted with CH2Cl2 (50 mL), washed with brine (3×20 mL), dried over MgSO4, and concentrated to dryness. The crude mixture was purified using flash column chromatography (MeOH/ CH2Cl2=1/30) to give the pure products.

Reference： [1]Gang, Fang-li; Zhu, Feng; Li, Xiao-ting; Wei, Jie-lu; Wu, Wen-jun; Zhang, Ji-wen [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 16, p. 4644 - 4649]

61
[ 1586765-00-5 ]
[ 118-61-6 ]
[ 2254004-68-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium carbonate In acetone for 10h; Reflux;	17 4.4.17 Ethyl 2-[2-(adamant-1-yl)prop-2-en-1-yloxy]benzoate (44) The solution of 2-(adamant-1-yl)-3-bromopropene (43) [ 99 ] (20 mmol), ethyl salicylate (21 mmol), and sodium carbonate (21 mmol) in 10 ml of acetone is refluxed for 10 h. The reaction mixture is poured into 100 ml of water and extracted with toluene (3 * 15 ml). The combined organic layers are washed with water and dried with sodium sulfate. The solvent is removed under reduced pressure and the product is purified by chromatography (eluent - petroleum ether). Colorless oil; yield 85%; IR (KBr) υ (cm-1) = 3024, 2977 (С-Нar), 2900, 2846 (С-Нalk), 1720 (C=O), 1674, 1604 (С = C), 1450 (С-Н), 1303, 1268 (C-O), 1087 (СН = СНtrans), 756; MS, m/z: 340 (M+, 12), 295 (5), 204 (100), 176 (16), 159 (23), 135 (45), 133 (20), 93 (16), 79 (19); 1H NMR (400 MHz, CDCl3) δ 1.37 (t, 3Н, 3J = 7.1 Hz), 1.60-1.80 (m, 12Н), 1.99-2.08 (m, 3Н), 4.35 (q, 2Н, 2J = 7.1 Hz), 4.64 (s, 2Н), 5.05 (s, 1Н), 5.35 (s, 1Н), 6.93-6.97 (m, 2Н), 7.41 (td, 1Н, 3J = 7.5 Hz, 3J = 1.6 Hz), 7.77 (dd, 1Н, 3J = 1.6 Hz, 3J = 8 Hz); 13C NMR (100 MHz, CDCl3) δ 14.43, 28.68, 36.64, 36.94, 41.38, 60.95, 68.34, 109.55, 113.30, 120.18, 121.06, 131.61, 133.17, 151.98, 158.20, 166.70; elemental analysis calcd. for C22H28O3: C 77.61, H 8.29; found: C: 77.74; H: 8.23.

Reference： [1]Shiryaev, Vadim A.; Radchenko, Eugene V.; Palyulin, Vladimir A.; Zefirov, Nikolay S.; Bormotov, Nikolay I.; Serova, Olga A.; Shishkina, Larisa N.; Baimuratov, Marat R.; Bormasheva, Kseniya M.; Gruzd, Yulia A.; Ivleva, Elena A.; Leonova, Marina V.; Lukashenko, Anton V.; Osipov, Dmitry V.; Osyanin, Vitaliy A.; Reznikov, Alexander N.; Shadrikova, Vera A.; Sibiryakova, Anastasia E.; Tkachenko, Ilya M.; Klimochkin, Yuri N. [European Journal of Medicinal Chemistry, 2018, vol. 158, p. 214 - 235]

62
[ 118-61-6 ]
[ 119171-39-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium carbonate / butanone / 48 h / Heating / reflux 2.1: sodium hydroxide; water / ethanol / 2 h / 50 °C 2.2: 5 °C / pH 2

Reference： [1]Current Patent Assignee: NOVO NORDISK A/S - WO2008/116141, 2008, A1

63
[ CAS Unavailable ]
[ 118-61-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
41.42%	With potassium carbonate In acetonitrile at 75℃; for 12h; Inert atmosphere;	Ethyl 2-(2-((3R,4aR,6aS,7R,10bR)-3-cyclopentyl-6a,10b-dimethyl-8-dihydromethylene decahydro-1H-naphtho[2,1-d][1,3]dioxin-7-yl)ethoxy)benzoate Step 1 Ethyl 2-(2-((3R,4aR,6aS,7R,10bR)-3-cyclopentyl-6a,10b-dimethyl-8-dihydromethylene decahydro-1H-naphtho[2,1-d][1,3]dioxin-7-yl)ethoxy)benzoate (3R,4aR,6aS,7R,10bR)-7-(2-bromoethyl)-3-cyclopentyl-6a,10b-dimeth yl-8-methylenedecahydro-1H-naphtho[2,1-d][1,3]dioxin (400.00 mg, 972.27 umol) was dissolved in acetonitrile (10.00 mL), and potassium carbonate (134.38 mg, 972.27 umol) and ethyl 2-hydroxybenzoate (193.87 mg, 1.17 mmol) were successively added, and then stirred under nitrogen atmosphere at 75° C. for 12 hours. The reaction was quenched with 30 mL water and then extracted with ethyl acetate (30 mL). The organic phase was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography (silica, petroleum ether/ethyl acetate=8/1) to give ethyl 2-(2-((3R,4aR,6aS,7R,10bR)-3-cyclopentyl-6a,10b-dimethyl-8-dihydromethylene decahydro-1H-naphtho[2,1-d][1,3]dioxin-7-yl)ethoxy)benzoate (a yellow oil, 200 mg, yield: 41.42%). 1H NMR (400 MHz, CDCl3) 7.74 (dd, J=1.5, 7.8 Hz, 1H), 7.44-7.36 (m, 1H), 6.95 (t, J=7.5 Hz, 1H), 6.89 (d, J=8.3 Hz, 1H), 4.86 (s, 1H), 4.67-4.56 (m, 2H), 4.36 (q, J=7.0 Hz, 2H), 4.19-4.09 (m, 1H), 4.03 (d, J=11.3 Hz, 1H), 3.92-3.79 (m, 1H), 3.55-3.37 (m, 2H), 2.41 (d, J=13.3 Hz, 1H), 2.27 (dq, J=3.1, 13.2 Hz, 1H), 2.14-2.02 (m, 2H), 2.01-1.84 (m, 4H), 1.83-1.75 (m, 1H), 1.73-1.63 (m, 3H), 1.62-1.57 (m, 1H), 1.55-1.43 (m, 4H), 1.42-1.32 (m, 7H), 1.28-1.19 (m, 3H), 0.78 (s, 3H).

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD.; HEILONGJIANG ZBD PHARMACEUTICAL CO LTD - US2018/346438, 2018, A1 Location in patent: Paragraph 0178-0183

64
[ 118-61-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
96%	With hydroxylamine hydrochloride; sodium carbonate at 20℃; Milling;	4 Preparation of salicyl hydroxamic acid Control the reactor temperature to room temperature, and the purity of 16.60 parts is 99%.Ethyl salicylatewith6.95 parts of hydroxylamine hydrochloride Add to the reactor, add and then10.60 parts of sodium carbonate is added to the above reactor, ground or ball milled,The reaction takes 5 to 30 minutes,Sodium salicylate salicylate. After drying, the purity was 72.3%.(The impurity was sodium chloride or sodium carbonate), and the yield was 96%. The product was confirmed as the target product by mass spectrometry

Reference： [1]Current Patent Assignee: HUNAN UNIVERSITY OF CHINESE MEDICINE - CN108929246, 2018, A Location in patent: Paragraph 0037-0039

65
[ 75-36-5 ]
[ 118-61-6 ]
[ 16475-93-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With aluminum (III) chloride In dichloromethane at 0 - 20℃; for 6h;	1.1 (1) Preparation of ethyl 2-hydroxy-5-acetylbenzoate Add 30 g (0.181 mol) of ethyl salicylate and 300 ml to a 500 ml three-necked vialDichloromethane, cooled to 0 ° C, and 18.4 g (0.231 mol) of acetyl chloride was added thereto.Stir well to obtain a mixed solution. Weighing 60.4 g (0.457 mol) of anhydrous AlCl3,In order to avoid a violent exotherm, add the mixed solution in portions, about 6 g of aluminum trichloride each time.After about 10 additions, each interval is about 3 minutes. After the addition, it naturally rises to room temperature for 6 hours.The reaction solution after the reaction was slowly poured into 300 g of ice, and the mixture was stirred and layered.The organic phase was washed twice with water and then washed once with saturated sodium bicarbonate solution.Wash once with saturated saline solution,The organic layer was dried over anhydrous sodium sulfate.Filtered and dried to give a solidEthyl 2-hydroxy-5-acetylbenzoate 33.2 g, yield 88%.

Reference： [1]Current Patent Assignee: JINAN UNIVERSITY (GUANGZHOU); DONGGUAN CHUANGSU BIOLOGICAL TECH - CN109678707, 2019, A Location in patent: Paragraph 0040-0043

66
[ 683-08-9 ]
[ 118-61-6 ]
[ 2674205-93-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With lithium diisopropyl amide In tetrahydrofuran at -30 - 0℃; for 2h;	2.1. Synthesis of diethyl (2-(2-hydroxyarylo)-2-oxoethyl)phosphonates 10a-c General procedure: The solution of diethyl methylphosphonate 9 (1.52 g, 10.0 mmol) and ethyl salicylate 8a-c (10.0mmol) in THF (20 mL) was cooled to -30° C and LDA generated from n-butyllithium (14 mL of 2.5 M solution in hexanes, 35.0 mmol) and diisopropylamine (4.95 mL 35.0 mmol) in THF (20.0 mL) was added dropwise maintaining the temperature bellow -10° C. The mixture was stirred for 2 hour at 0 °C and the solution was quenched by adding saturated ammonium chloride (100 mL). The water layer was extracted with DCM (3 × 50 mL), the organic layers were combined, washed with water, brine and dried over MgSO4. Filtration and concentration of the filtrate gave the crude product, which was purified by column chromatography on silica gel (ethyl DCM/Acetone = 10 : 1) to provide the desired product. Diethyl (2-(2-hydroxyphenyl)-2-oxoethyl)phosphonate (10a) (2.17 g, 80%). Yellow oil. 31P NMR (101 MHz, Chloroform-d) δ 19.69.1H NMR (250 MHz, Chloroform-d) δ 1.29 (t, J = 7.1 Hz, 6H), 3.63 (d, J = 22.8 Hz, 2H), 3.94 - 4.34 (m, 4H), 6.74 - 7.07 (m, 2H), 7.49 (ddd, J = 8.5, 7.1, 2.0 Hz, 1H), 7.68 - 8.07 (m1H), 11.81 - 12.14 (m, 1H). 13C NMR (63 MHz, Chloroform-d) δ 16.29 (d, J = 6.3 Hz), 38.66 (d, J = 130.0 Hz), 62.88 (d, J = 6.6 Hz), 118.50 , 119.11 , 119.49 , 131.62 , 137.19 , 162.94 , 197.93 (d, J = 6.2 Hz). Anal. Calcd for C12H17O5P: C, 52.94; H, 6.29. Found: C, 52.72; H, 6.43.

Reference： [1]Kedzia, Jacek; Bartosik, Tomasz; Drogosz, Joanna; Janecka, Anna; Krajewska, Urszula; Janecki, Tomasz [Molecules, 2019, vol. 24, # 10]

67
[ 380430-53-5 ]
[ 118-61-6 ]

Reference： [1]Journal of Organic Chemistry,2020,vol. 85,p. 2040 - 2047

68
[ 637-69-4 ]
[ 118-61-6 ]
[ 875884-45-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With tert.-butylhydroperoxide; copper diacetate In acetonitrile at 80℃; for 15h;	General procedure for the synthesis of 2-acetylphenyl 4-methoxybenzoate General procedure: To an oven-dried pressure tube charged with 2-acetylphenol 1a(68.0 mg, 0.5 mmol), Cu(OAc)2 (18.0 mg, 20 mol %, 0.1 mmol) andTBHP (0.50 mL, 2.50 mmol, 5.5 M in decane) in MeCN (1.0 mL) was added 4-methoxystyrene 2a (134 mg, 1.0 mmol). The resultant reaction mixture was allowed to stir in pressure tube at 80 C for 15 h. After completion of reaction as monitored by TLC, the reaction mixture was cooled at room temperature and evaporated onto silica gel. Purication of product by silica gel column chromatography (n-hexane/EtOAc, 15:1) furnished the 2-acetylphenyl 4-methoxybenzoate 3aa (109 mg) in 81% yield.

Reference： [1]Kumar, Upendra; Sharma, Ajay; Kumar, Naveen; Pandey, Satyendra Kumar [Tetrahedron, 2021, vol. 84]

69
[ 64-17-5 ]
[ 444-30-4 ]
[ 118-61-6 ]

Yield	Reaction Conditions	Operation in experiment
53%	With water; potassium carbonate In toluene at 120℃; for 12h;	2. General procedure for the reaction General procedure: 1 (0.2 mmol, 1.0 equiv.), 2 (0.24mmol, 1.2 equiv.), K2CO3 (0.4 mmol, 2.0 equiv.), and toluene/H2O (V/V = 95:5, 2.0 mL) were added to a test tube at 120 °C in an oil bath under air overnight. After the disappearance of the substrate as indicated by TLC, the mixture was extracted by DCM (3 × 5 mL). The organic layers were combined and dried by Na2SO4. The solvent was removed under vacuum and the residue was purified by silica gel chromatography, using a mixture of petroleum ether/ethyl acetate to give the desired product 3.

Reference： [1]Lin, Chuankai; Liu, Jin-Biao; Wang, Ruixiang; Xie, Huilin [Tetrahedron Letters, 2022, vol. 89]

Recommend Products

Same Skeleton Products

Related Products

Isomers

Technical Information

• Acidity of Phenols • Acyl Group Substitution • Alcohols Convert Acyl Chlorides into Esters • Alcoholysis of Anhydrides • Alkyl Halide Occurrence • Amines Convert Esters into Amides • An Alkane are Prepared from an Haloalkane • Benzylic Oxidation • Birch Reduction • Birch Reduction of Benzene • Blanc Chloromethylation • Bouveault-Blanc Reduction • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Claisen Condensations Produce β-Dicarbonyl Compounds • Claisen Condensations Produce β-Dicarbonyl Compounds • Complete Benzylic Oxidations of Alkyl Chains • Complete Benzylic Oxidations of Alkyl Chains • Complex Metal Hydride Reductions • Conjugate Additions of p-Benzoquinones • Conversion of Amino with Nitro • Convert Esters into Aldehydes Using a Milder Reducing Agent • Decarboxylation of 3-Ketoacids Yields Ketones • Decomposition of Arenediazonium Salts to Give Phenols • Deprotection of Cbz-Amino Acids • Deprotonation of Methylbenzene • Diazo Coupling • Directing Electron-Donating Effects of Alkyl • Electrophilic Chloromethylation of Polystyrene • Electrophilic Substitution of the Phenol Aromatic Ring • Ester Cleavage • Ester Hydrolysis • Etherification Reaction of Phenolic Hydroxyl Group • Friedel-Crafts Alkylation of Benzene with Acyl Chlorides • Friedel-Crafts Alkylation of Benzene with Carboxylic Anhydrides • Friedel-Crafts Alkylation of Benzene with Haloalkanes • Friedel-Crafts Alkylation Using Alkenes • Friedel-Crafts Alkylations of Benzene Using Alkenes • Friedel-Crafts Alkylations Using Alcohols • Friedel-Crafts Reaction • Grignard Reagents Transform Esters into Alcohols • Groups that Withdraw Electrons Inductively Are Deactivating and Meta Directing • Halogenation of Benzene • Halogenation of Phenols • Hantzsch Pyridine Synthesis • Hydrogenation to Cyclohexane • Hydrogenolysis of Benzyl Ether • Ketones Undergo Mixed Claisen Reactions to Form β-Dicarbonyl Compounds • Kolbe-Schmitt Reaction • Nitration of Benzene • Nucleophilic Aromatic Substitution • Nucleophilic Aromatic Substitution with Amine • Oxidation of Alkyl-substituted Benzenes Gives Aromatic Ketones • Oxidation of Phenols • Pechmann Coumarin Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Reactions of Benzene and Substituted Benzenes • Reactions with Organometallic Reagents • Reduction of an Ester to an Alcohol • Reduction of an Ester to an Aldehyde • Reductive Removal of a Diazonium Group • Reimer-Tiemann Reaction • Reverse Sulfonation——Hydrolysis • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Sulfonation of Benzene • The Acylium Ion Attack Benzene to Form Phenyl Ketones • The Claisen Rearrangement • The Cycloaddition of Dienes to Alkenes Gives Cyclohexenes • The Nitro Group Conver to the Amino Function • Transesterification • Vilsmeier-Haack Reaction

Historical Records

Related Functional Groups of
[ 118-61-6 ]

Aryls

[ 6520-83-8 ]

Ethyl 2-methoxy-6-methylbenzoate

Similarity: 0.96

[ 87-20-7 ]

Isopentyl 2-hydroxybenzoate

Similarity: 0.96

[ 5985-24-0 ]

Dimethyl 4-hydroxyisophthalate

Similarity: 0.96

[ 79128-78-2 ]

2-Hydroxy-5-(methoxycarbonyl)benzoic acid

Similarity: 0.96

[ 5870-38-2 ]

Diethyl 2,5-dihydroxyterephthalate

Similarity: 0.92

Esters

[ 6520-83-8 ]

Ethyl 2-methoxy-6-methylbenzoate

Similarity: 0.96

[ 87-20-7 ]

Isopentyl 2-hydroxybenzoate

Similarity: 0.96

[ 5985-24-0 ]

Dimethyl 4-hydroxyisophthalate

Similarity: 0.96

[ 79128-78-2 ]

2-Hydroxy-5-(methoxycarbonyl)benzoic acid

Similarity: 0.96

[ 14963-96-3 ]

4-Methoxyisobenzofuran-1,3-dione

Similarity: 0.92

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	Inquiry	{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]}	{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price) ]}	{[ item.pr_usastock ]}		{[ item.pr_chinastock ]}	{[ item.pr_remark ]}

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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

[ CAS No. 118-61-6 ] {[proInfo.proName]}

Quality Control of [ 118-61-6 ]

Related Doc. of [ 118-61-6 ]

Product Details of [ 118-61-6 ]

Calculated chemistry of [ 118-61-6 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 118-61-6 ]

Application In Synthesis of [ 118-61-6 ]

[ 118-61-6 ] Synthesis Path-Upstream 1~5

[ 118-61-6 ] Synthesis Path-Downstream 1~69

Technical Information

Related Functional Groups of [ 118-61-6 ]

Aryls

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 118-61-6 ]