[ CAS No. 25081-39-4 ] {[proInfo.proName]}

Name: 25081-39-4|Methyl 3,5-dimethylbenzoate|97%
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Quality Control of [ 25081-39-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 25081-39-4 ]

Product Details of [ 25081-39-4 ]

CAS No. :	25081-39-4	MDL No. :	MFCD00077971
Formula :	C₁₀H₁₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PEVXENGLERTHJE-UHFFFAOYSA-N
M.W :	164.20	Pubchem ID :	32786
Synonyms :

Calculated chemistry of [ 25081-39-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.3
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.65
TPSA :	26.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.53 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.5
Log Po/w (XLOGP3) :	2.5
Log Po/w (WLOGP) :	2.09
Log Po/w (MLOGP) :	2.55
Log Po/w (SILICOS-IT) :	2.64
Consensus Log Po/w :	2.46

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.67
Solubility :	0.35 mg/ml ; 0.00213 mol/l
Class :	Soluble
Log S (Ali) :	-2.7
Solubility :	0.329 mg/ml ; 0.00201 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.24
Solubility :	0.0947 mg/ml ; 0.000577 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.33

Safety of [ 25081-39-4 ]

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

Application In Synthesis of [ 25081-39-4 ]

* 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 [ 25081-39-4 ]
Downstream synthetic route of [ 25081-39-4 ]

[ 25081-39-4 ] Synthesis Path-Upstream 1~13

1
[ 499-06-9 ]
[ 67-56-1 ]
[ 25081-39-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	at 55 - 60℃; for 4 h; Autoclave	General procedure: benzoic acid (Table 3, entry 1) (1.0 g,0.0081 mol), bromobenzene (0.125 g, 0.0081 mol), 10percent palladium on carbon(50percent wet) (0.2 g) and methanol (3 mL) were placed in autoclave vessel. Autoclave was pressurized with 1–2 bar of nitrogen followed by 1–2 bar of hydrogen gas and then put under the desired pressure of hydrogen (5–6 bar).The reaction mixtures are then warmed to 55–60 C temperature and stirredfor 4 h at 300 rpm. After reaction, the catalyst was filtered through celite bed.Filtrate was added with water (30 mL). The reaction mixture was extracted with isopropyl acetate (2 15 mL). The combined organic layers were washedwith 5percent aqueous sodium bicarbonate solution (2 15 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated under vacuum togive of methyl benzoate product

Reference： [1] Helvetica Chimica Acta, 1996, vol. 79, # 7, p. 1967 - 1979
[2] Journal of Organic Chemistry, 2006, vol. 71, # 19, p. 7205 - 7213
[3] Monatshefte fur Chemie, 1996, vol. 127, # 2, p. 185 - 200
[4] European Journal of Organic Chemistry, 2009, # 26, p. 4480 - 4485
[5] Tetrahedron Letters, 2013, vol. 54, # 42, p. 5690 - 5694
[6] Journal of Medicinal Chemistry, 1980, vol. 23, # 11, p. 1198 - 1201
[7] Angewandte Chemie - International Edition, 1998, vol. 37, # 13-14, p. 1846 - 1850
[8] Tetrahedron, 2009, vol. 65, # 22, p. 4298 - 4303
[9] Tetrahedron Letters, 2009, vol. 50, # 49, p. 6803 - 6806
[10] Organic and Biomolecular Chemistry, 2012, vol. 10, # 5, p. 1088 - 1092
[11] Comptes Rendus Chimie, 2015, vol. 18, # 12, p. 1320 - 1327
[12] Synlett, 2017, vol. 28, # 11, p. 1373 - 1377
[13] Journal of Agricultural and Food Chemistry, 2018, vol. 66, # 44, p. 11797 - 11805

2
[ 499-06-9 ]
[ 25081-39-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sulfuric acid In methanol	Example 1 Preparation of methyl-3,5-dimethyl-benzoate A solution of 3,5-dimethyl benzoic acid (25 g, 0.17 mol) in methanol (250 ml) was treated with sulfuric acid (1 ml, cat. amount) and heated to reflux. After 10 hours, the solution was cooled to room temperature, concentrated to approximately 1/2 volume and poured into 200 ml of crushed ice. The mixture was extracted twice with 200 ml portions of diethyl ether. The organic phase was extracted with saturated aqueous sodium carbonate, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting solid was recrystallized from hexanes to yield the product (24.5 g, 90percent yield) as volatile white plates. mp=32°-35° C. (lit. mp=35°-36° C.)
90%	With sulfuric acid In methanol	EXAMPLE 1 Preparation of methyl-3,5-dimethyl-benzoate: A solution of 3,5-dimethyl benzoic acid (25 g, 0.17 mol) in methanol (250 ml) was treated with sulfuric acid (1 ml, cat. amount) and heated to reflux. After 10 hours, the solution was cooled to room temperature, concentrated to approximately 1/2 volume and poured into 200 ml of crushed ice. The mixture was extracted twice with 200 ml portions of diethyl ether. The organic phase was extracted with saturated aqueous sodium carbonate, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting solid was recrystallized from hexanes to yield the product (24.5 g, 90percent yield) as volatile white plates. mp=32°-35° C. (lit. mp=35°-36° C.)

Reference： [1] Patent: US5342934, 1994, A,
[2] Patent: US5599926, 1997, A,
[3] Bulletin de la Societe Chimique de France, 1948, p. 593,596

3
[ 4749-37-5 ]
[ 866918-70-9 ]
[ 25081-39-4 ]

Reference： [1] Angewandte Chemie - International Edition, 2005, vol. 44, # 31, p. 4914 - 4917

4
[ 67-56-1 ]
[ 5779-95-3 ]
[ 25081-39-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	for 3 h; Reflux	General procedure: The starting aldehydematerials (1 mmol) were dissolved in MeOH (5 mL),and Oxone (1 mmol) and 10 mol percent of In(OTf)3 were added atroom temperature. The reaction mixture was heated at reflux,and was monitored for completion by TLC. After the reactionmixture was filtered, the filtrate was condensed using arotary evaporator. Flash column chromatography on silica gelfurnished the corresponding products, which were confirmedby spectroscopy.

Reference： [1] Chemical and Pharmaceutical Bulletin, 2013, vol. 61, # 8, p. 870 - 872

5
[ 4919-37-3 ]
[ 25081-39-4 ]

Reference： [1] Patent: US6090836, 2000, A,

6
[ 51329-15-8 ]
[ 80-48-8 ]
[ 25081-39-4 ]

Reference： [1] Chemical Communications, 2017, vol. 53, # 73, p. 10180 - 10183

7
[ 67-56-1 ]
[ 108-67-8 ]
[ 25081-39-4 ]

Reference： [1] Green Chemistry, 2016, vol. 18, # 19, p. 5122 - 5126

8
[ 67-56-1 ]
[ 6613-44-1 ]
[ 25081-39-4 ]

Yield	Reaction Conditions	Operation in experiment
2.98 g	for 2 h; Reflux	To the crude acid chloride (3), methanol (25.0 ml) was added,and heated under the reflux conditions for 2 h. The excess methanolwas evaporated in vacuo. The ester (4) was crystallized fromhexane yielding 2.98 g (55percent), mp. = 26–29 C.

Reference： [1] Bulletin de la Societe Chimique de France, 1948, p. 593,596
[2] Journal of Molecular Structure, 2013, vol. 1048, p. 172 - 178

9
[ 556-96-7 ]
[ 25081-39-4 ]

Reference： [1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 23, p. 5033 - 5040

10
[ 22445-41-6 ]
[ 25081-39-4 ]

Reference： [1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 23, p. 5033 - 5040

11
[ 186581-53-3 ]
[ 499-06-9 ]
[ 25081-39-4 ]

Reference： [1] Magnetic Resonance in Chemistry, 2004, vol. 42, # 10, p. 844 - 851
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 23, p. 5033 - 5040

12
[ 675-09-2 ]
[ 624-48-6 ]
[ 50919-64-7 ]
[ 25081-39-4 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1992, vol. 29, # 4, p. 811 - 813

13
[ 675-09-2 ]
[ 624-49-7 ]
[ 50919-64-7 ]
[ 25081-39-4 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1992, vol. 29, # 4, p. 811 - 813

[ 25081-39-4 ] Synthesis Path-Downstream 1~88

1
[ 25081-39-4 ]
[ 29333-41-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In acetonitrile; at 75 - 80℃; for 3h;	A mixture of 3,5-dimethylbenzoic acidMethyl ester82 g (0.5 mol),AIBN (0.5 g) and acetonitrile (500 mL) were added to the reaction flask,NBS180 g (1.0 mol) was added and heated to reflux at 75 to 80 C with stirring,Stirring 3h, the reaction is complete, below 60 under reduced pressure, cold to room temperature,250 mL of dichloromethane was added, followed by 50 mL of 10% sodium sulfite solution,10% sodium carbonate solution 50mL, purified water 50mL washing,Dried over anhydrous sodium sulfate and concentrated at 35-40 C to give a yellow oil.Recrystallization from anhydrous ethanol (300 mL) gave 90 g of white solid crystals,Yield 85.0%
56%		Methyl 3,5-bis[[bis(2-pyridylmethyl)amino]methyl]benzoate (3) Methyl 3,5-bis(bromomethyl)-benzoate (500 mg, 1.6 mmol) and di-(2-picolyl)-amine (800 mg, 725 muL, 4 mmol) were dissolved in ACN followed by the addition of dry K2CO3 (1.1 g, 7.9 mmol). The reaction mixture was refluxed overnight under reflux condenser equipped with a CaCl2 tube. The reaction mixture was filtered and filtrate was evaporated under reduced pressure. Yellow residue was purified by flash chromatography (Al2O3 neutral, firstly AcOEt was used to elute impurities and then MeOH/AcOEt=1:9 (v/v)) affording a pure product as a yellow oil. Yield: 850 mg (95%). 1H NMR (500 MHz, CDCl33) delta 8.51 (m, 4H), 7.94 (d, J=1.5 Hz, 2H), 7.70 (s, 1H), 7.61 (m, 8H), 7.12 (m, 4H), 3.92 (s, 3H), 3.81 (s, 8H), 3.73 (s, 4H). 13C NMR (101 MHz, CDCl3) delta 197.9, 167.1, 159.5, 148.9, 139.7, 136.2, 133.8, 130.2, 128.7, 122.8, 121.9, 60.1, 58.2, 52.0. MS (ESI, m/z): calculated: 558.7 observed: 559.5 [M+H]+.
55%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;	Example 2 Preparation of methyl-3,5-bis(bromomethyl)-benzoate A solution of <strong>[25081-39-4]methyl-3,5-dimethyl-benzoate</strong> (16.8 g, 0.10 mol) in carbon tetrachloride (150 ml) was treated with N-bromosuccinimide (35.6 g, 0.20 mmol), and benzoyl peroxide (500 mg, cat. amount), and heated to reflux. After 3 hours, the mixture was cooled to room temperature and filtered through a sintered glass funnel. The filtrate was concentrated under reduced pressure and recrystallized from diethyl ether/hexanes (1:1) to yield the product (18.0 g, 55% yield) as a granular white solid. mp 64-70C. (lit. mp 65-69 C.); TLC (20% ethyl acetate/hexanes): Rf =0.65 (UV active, CAM stain)

55%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;	EXAMPLE 2 Preparation of methyl-3,5-bis(bromomethyl)-benzoate: A solution of <strong>[25081-39-4]methyl-3,5-dimethyl-benzoate</strong> (16.8 g, 0.10 mol) in carbon tetrachloride (150 ml) was treated with N-bromosuccinimide (35.6 g, 0.20 mmol), and benzoyl peroxide (500 mg, cat. amount), and heated to reflux. After 3 hours, the mixture was cooled to room temperature and filtered through a sintered glass funnel. The filtrate was concentrated under reduced pressure and recrystallized from diethyl ether/hexanes (1:1) to yield the product (18.0 g, 55% yield) as a granular white solid. mp 64-70 C. (lit. mp 65-69 C.); TLC (20% ethyl acetate/hexanes): Rf =0.65 (UV active, CAM stain)
45%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); Methyl formate; for 20h;Reflux;	A mixture of the above <strong>[25081-39-4]methyl 3,5-dimethylbenzoate</strong> (5, 29.3 g, 178 mmol), N- bromosuccinimide (NBS, 111 g, 623 mmol) and a spatula of azobisisobutyronitrile in methyl formate (450 mL) was irradiated with visible light while heating to reflux for 20 hours. The solvent was evaporated and the residue was dissolved in dichloromethane (200 mL). The precipitated succinimide was filtered off and the filtrate was washed with saturated aqueous solution of sodium sulfite (2 x 150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (Silicagel 60, 0.040-0.063 mm; eluent: hexane/ethyl acetate 15: 1). The product was crystallized from ethyl acetate/cyclohexane mixture giving methyl 3,5-bis(bromomethyl)benzoate 6 as white solid. Yield : 25.6 g (45%). RF (Si02, hexanes/ethyl acetate 9: 1) : 0.50. JH NMR spectrum (300 MHz, CDCI3, deltaEta) : 8.02-7.95 (m, 2 H); 7.62 (s, 1 H); 4.51 (s, 4 H); 3.94 (s, 3 H).
30%	With N-Bromosuccinimide; dibenzoyl peroxide; In chloroform; for 3h;Inert atmosphere; Reflux;	The overall synthetic plan for the bicyclization scaffold is shown in Scheme 2. To a 50-mL round-bottom flask charged with<strong>[25081-39-4]methyl 3,5-dimethylbenzoate</strong> (2.0 g, 12.2 mmol) in carbon tetrachloride (20 mL, sparged with nitrogen) was added N-bromosuccinimide (4.25 g, 23.9 mmol) and benzoyl peroxide (6O mg) as an initiator. The reaction was refluxed for 3 h under nitrogen atmosphere. The reaction mixture was cooled, and filtered. The filtrate was washed with water (20 mL), dried withMg504, and concentrated in vacuo. The crude product was recrystallized in petroleum ether to yield the title compound (1.2 g, 3.8 mmol) in 30% yield. ?HNMR (300 MHz, CDC13): 7.99 (s, 2H), 7.62 (s, 1H), 4.50 (s, 4H), 3.94 (s, 3H).
29%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Reflux;	This compound was prepared based on literature procedure with minor modifications as described below. Methyl-3, 5-dimethylbenzoate (1.0 g, 6.09 mmol), N-bromosuccinimide (2.16 g, 12.2 mmol), and benzoyl peroxide (29.5 mg, 0.12 mmol) were dissolved in 10 mL of carbon tetrachloride. The mixture was refluxed (with stirring) for 3 h. The reaction mixture was allowed to cool to 25 C and filtered and the filtrate was washed with 6 mL of water. The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The pale yellow residue was re-suspended in 50 mL of petroleum ether and kept at 4 C for 48 h. The precipitated product was purified by column chromatography on silica gel and eluted with 15: 1 (v/v) hexane/ethyl acetate. The product was obtained as white crystalline solid (564 mg, 1.76 mmol, 29% yield). 1 H NMR (300 MHz, CDCI3) d = 7.99 (s, 2H) 7.62 (s, 1 H) 4.50 (s, 4H) 3.94 (s, 3H).
25%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 3h;Reflux;	(iii) Methyl-3,5-bis(bromometylene)benzoate (5) The ester (4, 2.76 g, 0.0168 mol), N-bromosuccinimide (6.07 g, 0.0341 mol) and benzoyl peroxide (85 mg, 0.35 mmol) were placed in 100 ml round-bottom flask. Then dried carbon tetrachloride (25 ml) was added and heated under the reflux conditions for 3 h. After cooling to room temperature, the mixture was filtered and the solvent was evaporated in vacuo to obtain the crude product as residue (5.39 g). The crude product was crystallized from hexane to yield the dibromide (5): 1.37 g (25%), mp. 94-98 C. 1H NMR (300 MHz, CDCl3) delta: 8.00 (s, 2H, arom. H); 7.61 (s, 1H, arom. H); 4.50 (s, 4H, CH2Br); 3.93 ppm (s, 3H, COOCH3).
	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;	The chloromethyl compound used as starting material in the above process may be prepared as follows: A mixture of <strong>[25081-39-4]methyl 3,5-dimethylbenzoate</strong> (6 g), N-bromosuccinimide (13 g), benzoyl peroxide (50 mg) and carbon tetrachloride (150 ml) was heated under reflux for 1 h. The mixture was then cooled and filtered, the filtrate was evaporated to dryness under reduced pressure, and the residue was crystallized from cyclohexane to give methyl 3,5-bis(bromomethyl)benzoate mp. 99-101.

Reference： [1]Journal of Medicinal Chemistry,1980,vol. 23,p. 1198 - 1201
[2]Patent: CN104387332,2016,B .Location in patent: Paragraph 0026-0027
[3]Helvetica Chimica Acta,1996,vol. 79,p. 1967 - 1979
[4]Synthesis,2001,p. 2078 - 2080
[5]Green Chemistry,2011,vol. 13,p. 2161 - 2166
[6]European Journal of Organic Chemistry,2009,p. 4480 - 4485
[7]Journal of Organic Chemistry,1999,vol. 64,p. 8588 - 8593
[8]Organic and Biomolecular Chemistry,2011,vol. 9,p. 7697 - 7704
[9]Patent: US9377466,2016,B2 .Location in patent: Page/Page column 43; 44
[10]Patent: US5342934,1994,A
[11]Patent: US5599926,1997,A
[12]Chemistry - A European Journal,2006,vol. 12,p. 6841 - 6851
[13]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3780 - 3783
[14]ChemMedChem,2018,vol. 13,p. 1303 - 1307
[15]Patent: WO2019/92125,2019,A1 .Location in patent: Page/Page column 47; 48; 49
[16]European Journal of Organic Chemistry,2008,p. 3190 - 3199
[17]Chemical Communications,2013,vol. 49,p. 9158 - 9160
[18]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 271 - 273
[19]Tetrahedron Letters,2000,vol. 41,p. 7737 - 7741
[20]Angewandte Chemie - International Edition,2017,vol. 56,p. 1525 - 1529
Angew. Chem.,2017,vol. 129,p. 1547 - 1551,5
[21]Photochemical and Photobiological Sciences,2017,vol. 16,p. 1371 - 1374
[22]Patent: WO2018/89648,2018,A2 .Location in patent: Page/Page column 102; 103
[23]Angewandte Chemie - International Edition,2018,vol. 57,p. 17183 - 17188
Angew. Chem.,2018,vol. 130,p. 17429 - 17434,6
[24]Patent: WO2019/213662,2019,A1 .Location in patent: Paragraph 00201; 00204-00205
[25]Organic and Biomolecular Chemistry,2008,vol. 6,p. 2282 - 2294
[26]Journal of Molecular Structure,2013,vol. 1048,p. 172 - 178
[27]Journal of the American Chemical Society,2002,vol. 124,p. 10797 - 10809
[28]Organic and Biomolecular Chemistry,2007,vol. 5,p. 2940 - 2952
[29]Liebigs Annalen der Chemie,1979,p. 886 - 898
[30]Patent: US4935437,1990,A
[31]Tetrahedron,2009,vol. 65,p. 4298 - 4303
[32]Organic and Biomolecular Chemistry,2012,vol. 10,p. 1088 - 1092

2
[ 499-06-9 ]
[ 67-56-1 ]
[ 25081-39-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sulfuric acid; for 48h;Reflux;	1 3,5-Dimethylbenzoic acid (4, 27.6 g, 18.4 mmol) was suspended in methanol (80 mL) and treated with concentrated sulfuric acid (8 mL) . The mixture was refluxed for 2 days. After neutralization with sodium carbonate (50 g), the mixture was dissolved in water (250 mL) and extracted with diethyl ether (2 x 300 mL) . The organic phases were dried over anhydrous sodium sulfate, filtered and evaporated to dryness affording methyl 3,5-dimethylbenzoate 5 as pale yellow oil. Yield : 29.3 g (97%) . *H NM R spectrum (300 MHz, CDCI3, deltaEta) : 7.67 (s, 2 H) ; 7.19 (s, 1 H) ; 3.91 (s, 3 H) ; 2.37 (s, 6 H) .
87%	With bromobenzene; at 55 - 60℃; under 3750.38 - 4500.45 Torr; for 4h;Autoclave;	General procedure: benzoic acid (Table 3, entry 1) (1.0 g,0.0081 mol), bromobenzene (0.125 g, 0.0081 mol), 10% palladium on carbon(50% wet) (0.2 g) and methanol (3 mL) were placed in autoclave vessel. Autoclave was pressurized with 1-2 bar of nitrogen followed by 1-2 bar of hydrogen gas and then put under the desired pressure of hydrogen (5-6 bar).The reaction mixtures are then warmed to 55-60 C temperature and stirredfor 4 h at 300 rpm. After reaction, the catalyst was filtered through celite bed.Filtrate was added with water (30 mL). The reaction mixture was extracted with isopropyl acetate (2 15 mL). The combined organic layers were washedwith 5% aqueous sodium bicarbonate solution (2 15 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated under vacuum togive of methyl benzoate product
		General procedure: A mixture of benzoic acids (20.0 mmol), CH3OH (30.0 mL) were placed in a 100mL round-bottomed flask equipped with a magnetic stirrer. Stirring for 10 minutes in 0 C. Then thionyl chloride (1.5 eq.) was addedto the flask. The mixture was stirred under reflux 6h. The progress wasmonitored by TLC. After the reaction, the reaction system wereconcentrated to remove CH3OH and most of thionylchloride. Aftercooling, the H2O (50 mL) and EtOAc (30 mL) were added into thecontents. The aqueous phase was extracted with EtOAc (30 mL×3), andthe organic phase was washed with saturated aqueous NaHCO3 solutionand brine. Then it was dried over anhydrous Na2SO4, filtered, and concentrated to give the ester as a faint yellow solid (liquid). The step yield was 80%~95%.

Reference： [1]Helvetica Chimica Acta,1996,vol. 79,p. 1967 - 1979
[2]Patent: WO2019/92125,2019,A1 .Location in patent: Page/Page column 47; 48
[3]Journal of Organic Chemistry,2006,vol. 71,p. 7205 - 7213
[4]Monatshefte fur Chemie,1996,vol. 127,p. 185 - 200
[5]European Journal of Organic Chemistry,2009,p. 4480 - 4485
[6]Tetrahedron Letters,2013,vol. 54,p. 5690 - 5694
[7]Journal of Medicinal Chemistry,1980,vol. 23,p. 1198 - 1201
[8]Angewandte Chemie - International Edition,1998,vol. 37,p. 1846 - 1850
[9]Tetrahedron,2009,vol. 65,p. 4298 - 4303
[10]Tetrahedron Letters,2009,vol. 50,p. 6803 - 6806
[11]Organic and Biomolecular Chemistry,2012,vol. 10,p. 1088 - 1092
[12]Comptes Rendus Chimie,2015,vol. 18,p. 1320 - 1327
[13]Synlett,2017,vol. 28,p. 1373 - 1377
[14]Journal of Agricultural and Food Chemistry,2018,vol. 66,p. 11797 - 11805

3
[ 112043-57-9 ]
[ 25081-39-4 ]
[ 112043-58-0 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 391 - 395

4
[ 25081-39-4 ]
[ 39922-13-9 ]
C₁₀H₁₃O₂⁽¹⁺⁾ [ No CAS ]
[ 98-86-2 ]

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 951 - 954

5
[ 675-09-2 ]
[ 624-48-6 ]
[ 50919-64-7 ]
[ 25081-39-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1992,vol. 29,p. 811 - 813

6
[ 675-09-2 ]
[ 624-49-7 ]
[ 50919-64-7 ]
[ 25081-39-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1992,vol. 29,p. 811 - 813

7
[ 25081-39-4 ]
[ 109-70-6 ]
[ 111112-92-6 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 391 - 395

8
E-(1,3-dimethylbuta-1,3-dienyl)carbamic acid methyl ester [ No CAS ]
[ 4749-37-5 ]
[ 866918-70-9 ]
[ 25081-39-4 ]

Reference： [1]Angewandte Chemie - International Edition,2005,vol. 44,p. 4914 - 4917

9
[ 25081-39-4 ]
[ 145665-38-9 ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 7205 - 7213
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3780 - 3783

10
[ 25081-39-4 ]
[ 105995-42-4 ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 7205 - 7213
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3780 - 3783

11
[ 25081-39-4 ]
3,5-bis-[(9<i>H</i>-fluoren-9-ylmethoxycarbonylamino)-methyl]-benzoic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3780 - 3783

12
[ 25081-39-4 ]
[ 105995-43-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3780 - 3783

13
[ 25081-39-4 ]
3,5-Bis-(1,4,7,10-tetraaza-cyclododec-1-ylmethyl)-benzoic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 6841 - 6851

14
[ 25081-39-4 ]
C₃₀H₄₆N₈O₂⁽²⁺⁾*2Br^(1-) [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 6841 - 6851

15
[ 25081-39-4 ]
3,5-bis(di-t-butylphosphinomethyl)benzoate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 10797 - 10809

16
[ 25081-39-4 ]
[ 376364-28-2 ]

Reference： [1]Tetrahedron Letters,2001,vol. 42,p. 6459 - 6461

17
[ 25081-39-4 ]
[ 217192-38-6 ]

Reference： [1]Tetrahedron Letters,2001,vol. 42,p. 6459 - 6461

18
[ 25081-39-4 ]
[ 367927-29-5 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5814 - 5821

19
[ 25081-39-4 ]
lithium 3,5-bis(dimethoxyphosphorylmethyl)benzoate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5814 - 5821

20
[ 25081-39-4 ]
trilithium 3,5-bis(methylphosphonatomethyl)benzoic acid ethylphosphomatomethyl amide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5814 - 5821

21
[ 25081-39-4 ]
3C₁₆H₃₆N⁽¹⁺⁾*C₁₁H₁₃O₈P₂^(3-) [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5814 - 5821

22
[ 25081-39-4 ]
[ 75594-35-3 ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 7737 - 7741

23
[ 25081-39-4 ]
3,5-Bis-[(E)-2-(4',5'-bis-dodecylsulfanyl-[2,2']bi[[1,3]dithiolylidene]-4-yl)-vinyl]-benzoic acid methyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 7737 - 7741

24
[ 25081-39-4 ]
[ 318267-12-8 ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 7737 - 7741

25
[ 25081-39-4 ]
[ 318267-11-7 ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 7737 - 7741

26
[ 25081-39-4 ]
[ 206551-23-7 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4485 - 4499

27
[ 25081-39-4 ]
methyl 2-[{3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thienyl}carbonyl]amino}-3,5-dimethylbenzoate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4485 - 4499

28
[ 25081-39-4 ]
[ 252289-78-4 ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 8588 - 8593

29
[ 25081-39-4 ]
[ 224961-41-5 ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 8588 - 8593

30
[ 25081-39-4 ]
[ 252289-77-3 ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 8588 - 8593

31
[ 25081-39-4 ]
[ 185963-31-9 ]

Reference： [1]Angewandte Chemie - International Edition,1998,vol. 37,p. 1846 - 1850
[2]Helvetica Chimica Acta,1996,vol. 79,p. 1967 - 1979
[3]Patent: WO2019/92125,2019,A1

32
[ 25081-39-4 ]
C₁₂H₁₃NO₄ [ No CAS ]