[ CAS No. 98-66-8 ] {[proInfo.proName]}

Name: 98-66-8|4-Chlorobenzenesulfonic acid|98% (contains <5%H2O)
Brand: Ambeed
SKU: A212429
Rating: 96 (29 reviews)

,{[proInfo.pro_purity]}

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

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Quality Control of [ 98-66-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 98-66-8 ]

SDS Specification

Alternatived Products of [ 98-66-8 ]

Product Details of [ 98-66-8 ]

CAS No. :	98-66-8	MDL No. :	MFCD00065342
Formula :	C₆H₅ClO₃S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RJWBTWIBUIGANW-UHFFFAOYSA-N
M.W :	192.62	Pubchem ID :	7400
Synonyms :

Calculated chemistry of [ 98-66-8 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.31
TPSA :	62.75 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) :	-8.08 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.69
Log Po/w (XLOGP3) :	-0.85
Log Po/w (WLOGP) :	2.67
Log Po/w (MLOGP) :	1.71
Log Po/w (SILICOS-IT) :	0.87
Consensus Log Po/w :	1.02

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-0.84
Solubility :	28.1 mg/ml ; 0.146 mol/l
Class :	Very soluble
Log S (Ali) :	0.01
Solubility :	199.0 mg/ml ; 1.03 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-2.37
Solubility :	0.827 mg/ml ; 0.0043 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.16

Safety of [ 98-66-8 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P261-P280-P305+P351+P338-P310	UN#:	3261
Hazard Statements:	H302-H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 98-66-8 ]

* 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 [ 98-66-8 ]
Downstream synthetic route of [ 98-66-8 ]

[ 98-66-8 ] Synthesis Path-Upstream 1~6

1
[ 98-66-8 ]
[ 97-09-6 ]

Reference： [1] Chemische Berichte, 1891, vol. 24, p. 3188

2
[ 98-66-8 ]
[ 121-18-6 ]

Reference： [1] Grundlegende Operationen der Farbenchemie, 5.Aufl. <Wien 1943>, S.101,103,118,
[2] Chemische Berichte, 1891, vol. 24, p. 3188

3
[ 7664-93-9 ]
[ 98-66-8 ]
[ 121-18-6 ]
[ 100-00-5 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1867, vol. 143, p. 184
[2] Chemische Berichte, 1891, vol. 24, p. 3188

4
[ 98-66-8 ]
[ 97-08-5 ]

Reference： [1] Chemische Berichte, 1891, vol. 24, p. 3188

5
[ 64-17-5 ]
[ 98-66-8 ]
[ 33065-61-1 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 8, p. 1441 - 1445

6
[ 67-56-1 ]
[ 98-66-8 ]
[ 33065-61-1 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 8, p. 1441 - 1445

[ 98-66-8 ] Synthesis Path-Downstream 1~88

1
[ 98-66-8 ]
[ 98-67-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide at 300℃;
	With quicklime; water; copper at 180 - 200℃;
	With barium dihydroxide; water; copper at 180 - 200℃;

	With quicklime; water at 180 - 200℃; in Gegenwart von Kupferverbindungen;
	With barium dihydroxide; water at 180 - 200℃; in Gegenwart von Kupferverbindungen;

Reference： [1]Willson; Meyer,K.H. [Chemische Berichte, 1914, vol. 47, p. 3163]
[2]Current Patent Assignee: Boehringer & Soehne - DE288116, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159]
[3]Current Patent Assignee: Boehringer & Soehne - DE288116, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159]
[4]Current Patent Assignee: Boehringer & Soehne - DE288116, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159]
[5]Current Patent Assignee: Boehringer & Soehne - DE288116, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 12, p. 159]

2
[ 98-66-8 ]
[ 121-18-6 ]

Reference： [1]Grundlegende Operationen der Farbenchemie, 5.Aufl. <Wien 1943>, S.101,103,118,
[2]Chemische Berichte,1891,vol. 24,p. 3188

3
[ 98-66-8 ]
[ 108-90-7 ]
[ 80-07-9 ]

Yield	Reaction Conditions	Operation in experiment
11%	With sulfur trioxide; trifluoroacetic acid; at 40 - 100℃; for 8.5h;Inert atmosphere;Product distribution / selectivity;	In a dry 250 mL jacketed addition funnel, with pressure equalizing, maintained under a nitrogen blanket, fitted with an inlet tube connected to an oleum distillation set up, were introduced 213.67 g of TFA. The jacket of the addition funnel was heated to 45C and 75.02 g of SO3 vapors were slowly introduced into the TFA via a glass frit. The total time of addition was 2 hours. The mixture of trifluoroacetosulfate was then held at 45C for 3 hours and cooled down to 5C for storage. A blanket of nitrogen was maintained on the mixture at all time.In a dry 3-neck 250-mL round bottom flask, containing a PTFE-coated stir bar and fitted with a PTFE-coated thermocouple, a distillation receiver allowing returning the vapors to the mixture (Barrett trap) + reflux condenser + H2SO4 scrubber, and connected to the jacketed addition funnel containing the trifluoroacetosulfate, was introduced, under nitrogen, a third of thetrifluoraoacetate mixture prepared as described above (25.00 g SO3 +71.22 g TFA). 43.15 g of molten 4-chlorobenzene sulfonic acid (93 wt % pure) as prepared in comparative example 6 were added to the Barrett trap, along with 47.52 g of TFA. The trifluoroacetosulfate mixture was heated to 40C in the reaction flask. The mixture of 4-chlorobenzenesulfonic acid and TFA in the Barrett trap was then added slowly over 30 minutes to the reaction flask, under agitation. 24.61 g of MCB were then added to the Barrett trap and added slowly over 30 minutes to the reaction flask. The reaction medium was heated to 60C under agitation. The reaction medium was held at 60C for 3 hours. The temperature was increased to 100C with the Barrett trap in the collection position. 85.06 g of distillate were collected in the Barrett trap and removed. The Barrett trap was put in total reflux position again and the reaction medium was held at 100C for 5 hours.At the end of the reaction, the mixture was poured on 2,000 mL of deionized water. The precipitate formed was isolated by filtration, rinsed with more deionized water (2,000 mL) and dried at 60C under 0.13 atm for 20 hours. The dried solid (9.480 g) was analyzed by GC and shown to be4.4'-dichlorodiphenyl sulfone (98.9 % 4,4'-isomer), 11 % yield. Taking into account the isomer purity of the dichlorodiphenyl sulfone present in the starting 4-chlorobenzenesulfonic acid (97.3 %), the regioselectivity of the reaction with the trifluoroacetosulfate is 99.6 %.
2%	With acetic anhydride; at 100 - 120℃; for 3h;Product distribution / selectivity;	A mixture of 4-chlorobenzenesulfonic acid was produced by the reaction of MCB with sulfur trioxide. The mixture contained 70 wt %chlorobenzenesulfonic acid (96.5 % 4-isomer), 21 wt % dichlorodiphenyl sulfone (94.2 % 4,4'-isomer), 7 wt % H2S04 and 2 wt % MCB.In a dry 3-neck 250-mL round bottom flask, fitted with a thermocouple, a distillation receiver allowing returning the vapors to the mixture (Barrett trap) + reflux condenser + silicone oil bubbler, and containing a PTFE-coated stir bar, were introduced successively : 1. 40.98 g of the chlorobenzenesulfonic acid mixture (= 28.69 g acid, 8.61 g sulfone)2. 18.15 g of acetic anhydride.The 3 neck of the flask was then sealed with a stopper. The mixture was heated to 120C under total reflux conditions and held at 120C for 20 minutes. Then, at 120C, 69.74 g of MCB were added. The temperature of the reaction medium was decreased to 100C under total reflux conditions. The reaction medium was held at 100C for 3 hours. At the end of the reaction, the reaction medium was poured on 1,000 mL of deionized water. The precipitate formed was isolated by filtration, rinsed with more deionized water (1,000 mL) and dried at 60C/0.3 atm for 20 hours. The dried solid (8.95 g) was analyzed by GC and shown to be 4,4'-dichlorodiphenyl sulfone (94.6 % 4,4'-isomer), 2 % yield.

Reference： [1]Patent: WO2012/143279,2012,A1 .Location in patent: Page/Page column 14; 15
[2]Patent: WO2012/143281,2012,A1 .Location in patent: Page/Page column 19; 20
[3]Justus Liebigs Annalen der Chemie,1923,vol. 433,p. 342

4
[ 108-90-7 ]
[ 98-66-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With 1,3-disulfonic acid imidazolonium chloride; In water; at 50℃; for 0.0833333h;Green chemistry;	General procedure: To a round-bottomed flask (10 mL) containing of 1,3-disulfonic acid imidazolium chloride ([Dsim]Cl) (2 mmol, 0.513 g) were added water (2 mmol, 0.036 g) and the aromatic substrate (2mmol). The reaction mixture was stirred at 50 C for the requisite time. After the reaction was complete (monitored withTLC), CH2Cl2 (10 mL) was added and the reaction mixture stirred for 2 min. The organic solvent was removed, and the product was purified by short column chromatography.
	With sulfur trioxide; at 40℃; for 2h;exclusion of air humidity;Product distribution / selectivity;	Example 3Use of unstabilized sulfur trioxide and sulfur trioxide stabilized with BF3-dimethyl etherate in the sulfonation of chlorobenzene as a precursor of the preparation of 4,4'-dichlorodiphenyl sulfone64 g (0.8 mol) of sulfur trioxide which has been stabilized with different amounts of boron trifluoride dimethyl etherate was added with exclusion of air humidity at a maximum of 40 C. to 400 g (3.55 mol) of chlorobenzene within 120 min. The resulting solution can be used for synthesis of dichlorodiphenyl sulfone, for example according to U.S. Pat. No. 2,593,001. The ratio of the chlorobenzenesulfonic acid isomers formed as a function of the stabilizer content can be found in the table which follows. Boron-free sulfur trioxide was obtained in example 3 by distillation out of oleum. TABLE 1 Boron content [ppm] from BF3-DME 0 50 100 300 500 Ratio of 4-chloro- 95:1 92:1 89:1 60:1 61:1 benzenesulfonic acid to 2-chlorobenzenesulfonic acid
	With sulfur trioxide; at 45℃;exclusion of air humidity;Product distribution / selectivity;	Example 5The monochlorobenzene used in example 5 was obtained by additionally subsequently distilling the monochlorobenzene used in example 1 over P2O5 in a batch distillation column and hence purifying it. The monochlorobenzene used in example 5 comprised, according to gas chromatography separation and subsequent detection by means of flame ionization, the following secondary components: hydrocarbons having from 5 to 8 carbon atoms <1 ppm.With exclusion of air humidity, 680 g (8.5 mol) of freshly distilled sulfur trioxide were added at a maximum of 45 C. to 1914 g (17 mol) of monochlorobenzene. The pale brown solution (chlorobenzenesulfonic acid in monochlorobenzene) can be used to synthesize dichlorodiphenyl sulfone, for example according to U.S. Pat. No. 2,593,001.

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2020
[2]Tetrahedron Letters,2004,vol. 45,p. 6607 - 6609
[3]Synlett,2016,vol. 27,p. 1682 - 1684
[4]Justus Liebigs Annalen der Chemie,1867,vol. 143,p. 184
[5]Justus Liebigs Annalen der Chemie,1867,vol. 143,p. 102
[6]Justus Liebigs Annalen der Chemie,1923,vol. 433,p. 333
[7]Journal of the Chemical Society,1920,vol. 117,p. 1407
[8]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1926,vol. 182,p. 856
[9]Journal of the Chemical Society,1915,vol. 107,p. 1822
[10]Patent: US2011/263902,2011,A1 .Location in patent: Page/Page column 4
[11]Patent: US2011/263903,2011,A1 .Location in patent: Page/Page column 4

5
[ 67-56-1 ]
5-bromoindan-2-yl chlorobenzene-p-sulfonate [ No CAS ]
[ 98-66-8 ]
[ 33065-61-1 ]
5-bromo-2-methoxy-2,3-dihydro-1H-indene [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1993,p. 1441 - 1445

6
[ 98-64-6 ]
[ 98-66-8 ]

Reference： [1]Tetrahedron Letters,1990,vol. 31,p. 3893 - 3894

7
[ 64-17-5 ]
5-bromoindan-2-yl chlorobenzene-p-sulfonate [ No CAS ]
[ 98-66-8 ]
[ 33065-61-1 ]
5-Bromo-2-ethoxy-indan [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1993,p. 1441 - 1445

8
[ 98-66-8 ]
[ 1142-19-4 ]

Reference： [1]Synthesis,1982,p. 152 - 155
[2]Bulletin of the Chemical Society of Japan,1983,vol. 56,p. 3813 - 3817

9
[ 98-66-8 ]
[ 106-54-7 ]

Reference： [1]Tetrahedron Letters,1980,vol. 21,p. 4921 - 4924
[2]Tetrahedron Letters,1982,vol. 23,p. 4701 - 4704
[3]Bulletin of the Chemical Society of Japan,1983,vol. 56,p. 3802 - 3812

10
[ 94-25-7 ]
[ 98-66-8 ]
4-Amino-benzoic acid butyl ester; compound with 4-chloro-benzenesulfonic acid [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,1994,vol. 250,p. 161 - 166

11
[ 98-66-8 ]
[ 40496-65-9 ]
2-(3-Cyclohexenyl)ethylammonium p-chlorobenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether at 0℃;

Reference： [1]Asensio, Gregorio; Mello, Rossella; Boix-Bernardini, Carmen; Gonzalez-Nunez, Maria Elena; Castellano, Gloria [Journal of Organic Chemistry, 1995, vol. 60, # 12, p. 3692 - 3699]

12
[ 7664-93-9 ]
[ 98-66-8 ]
[ 121-18-6 ]
[ 100-00-5 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1867,vol. 143,p. 184

13
[ 26971-85-7 ]
[ 100-46-9 ]
[ 100-02-7 ]
[ 14309-92-3 ]
[ 98-66-8 ]
[ 10504-90-2 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile at 65℃;

Reference： [1]Choi, Jin Heui; Lee, Byung Choon; Lee, Hai Whang; Lee, Ikchoon [Journal of Organic Chemistry, 2002, vol. 67, # 4, p. 1277 - 1281]

14
[ 98-66-8 ]
[ 98-60-2 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; sulfur trioxide; In N,N-dimethyl-formamide;	it is disclosed that reacting a monosubstituted benzene with sulfur trioxide in the presence of at least a stoichiometric excess of thionyl chloride produces a mixture of aromatic sulfonyl chloride and diaryl sulfone. The reaction of p-chlorobenzenesulfonic acid with thionyl chloride in the presence of at least molar amounts of dimethylformamide to produce p-chlorobenzenesulfonyl chloride is disclosed in Gregory, U.S. Patent No. 2,888,486.

Reference： [1]Synlett,2011,p. 2671 - 2674
[2]Tetrahedron Letters,2003,vol. 44,p. 1499 - 1501
[3]Patent: EP62736,1982,A1

15
[ 591-50-4 ]
[ 98-66-8 ]
[ 61477-32-5 ]

Yield	Reaction Conditions	Operation in experiment
65%	With 3-chloro-benzenecarboperoxoic acid; In chloroform; at 20℃; for 2h;	General procedure: In a round-bottom flask, iodine benzene (10.0 mmol), sulfonic acid (11.0 mmol), and chloroform (10.0 mL) were added successively and the mixture was stirred for 5 minutes at room temperature. Then m-CPBA (11.0 mmol) was put in slowly and the reaction mixture was stirred at room temperature. After the reaction, the reaction mixture was filtered, and the solid was washed with ether.

Reference： [1]Synlett,2005,p. 2486 - 2488
[2]Synthetic Communications,2018,vol. 48,p. 1957 - 1965

16
[ 98-66-8 ]
[ 98-86-2 ]
[ 110143-20-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	With 1-iodo-propane; 3-chloro-benzenecarboperoxoic acid; In 2,2,2-trifluoroethanol; acetonitrile; at 20℃; for 8h;	General procedure: To a mixture solvent of MeCN-CF3CH2OH (7:3) (5 mL), ketone 1 (0.5 mmol), mCPBA (1.0 mmol), 1-iodopropane (0.125 mmol) and TsOH*H2O (1.25 mmol) were added. The resulting solution was stirred at rt for several hours. After the reaction completed, H2O (10 mL), satd aq Na2S2O3 (5 mL) and satd aq Na2CO3 (5 mL) were added to the mixture, then it was extracted with CH2Cl2 (3 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and the filtration was concentrated under reduced pressure. The residue was then purified on a silicagel plate (4:1 hexane-ethyl acetate) to furnish alpha-tosyloxyketones 2.
54%	With 1,1,1-trifluoro-2-iodoethane; boron trifluoride diethyl etherate; water; 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 35 - 40℃; for 8h;	General procedure: Ketone 1 (0.5 mmol), MCPBA (0.75 mmol), CF3CH2I (0.15 mmol), BF3*Et2O(1.5 mmol), H2O (3.0 mmol), and sulfonic acid 2 (1.0 mmol) were added to CH2Cl2(5mL). The resulting mixture was stirred at 35-40 C for 12 h. Then, water(10mL), saturated aqueous Na2S2O3 (5mL), and saturated aqueous Na2CO3(5mL) were poured into the reaction mixture. After separation of the organic layer,the water layer was extracted with CH2Cl2 (310 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative thin-layer chromatography (TLC) on silica gel using hexane-AcOEt (4:1) as eluent to give the pure product 3.

Reference： [1]Synlett,2009,p. 3360 - 3364
[2]Tetrahedron,2007,vol. 63,p. 4680 - 4687
[3]Tetrahedron Letters,2014,vol. 55,p. 5851 - 5854
[4]Synthetic Communications,2014,vol. 44,p. 3264 - 3270

17
[ 98-66-8 ]
[ 97-08-5 ]

Reference： [1]Chemische Berichte,1891,vol. 24,p. 3188

18
[ 98-66-8 ]
[ 97-09-6 ]

Reference： [1]Chemische Berichte,1891,vol. 24,p. 3188

19
[ 686350-63-0 ]
[ 98-66-8 ]
[ 686350-90-3 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 21℃;	4-CHLOROBENZENE sulfonate 4-CHLOROBENZENE SULFONIC ACID (19MG) was added to a solution of 4-{(1R)-2-[(6-{4-[3- (cyclopentylsulfonyl)phenyl]butoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol (55mg) (dissolved by gentle warming) in propan-2-ol (0. 5ml) at 21. After a few minutes crystals had separated out. These were collected, and rinsed with propan-2-ol to give crystals of the title compound, 8 (DMSO-d6) 9.40 (1H, s), 8.42 (2H, br s), 7.72-7. 67 (2H, m), 7.62-7. 55 (4H, m), 7.38 (2H, m), 7.32 (1H, d, J 2Hz), 7.05 (1H, dd, J 2, 8 HZ), 6.75 (1H, d, J 8Hz), 5.97 (1H, BRS), 5.00 (1H, v br s), 4.76 (1H, br d, J 9 Hz), 4.49 (2H, s), 3.75 (1H m), 3.32 (4H, partially obscured t), 3.10-2. 87 (4H, 2m), 2.71 (2H, t, J 7Hz), 1.90- 1.25 (20H, m). The XRPD pattern of this product is shown in Figure 1.

Reference： [1]Patent: WO2004/37773,2004,A1 .Location in patent: Page 66-67

20
[ 20859-02-3 ]
[ 98-66-8 ]
L-tert-leucine·p-chlorobenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.6%	In water; at 10 - 80℃; for 18h;	To pure water (12 ml) were added L-tert-leucine (3.94 g, 0.030 mol) and p-chlorobenzenesulfonic acid (5.79 g, 0.030 mol) and the mixture was treated at 80C to give a homogeneous solution. This solution was allowed to cool to 10C and the crystals were allowed to precipitate at 10C for 18 hr. The precipitated crystals were collected by filtration, washed with cold water (2 ml) and acetonitrile (15 ml) and vacuum dried at 40C for 5 hr to give L-tert-leucine·p-chlorobenzenesulfonate (5.65 g). The crystals were analyzed under HPLC analysis condition 1 to find that the L-tert-leucine content was 39.5 wt% and the rate of recovery was 56.6%. Furthermore, an analysis under HPLC analysis condition 2 revealed that the optical purity was 100%ee. Measurement by powder X-ray diffraction method (using CuKalpha ray as a radiation source) revealed a powder X-ray diffraction pattern as shown in Fig. 7. The melting point was 214-217C (decomposition).

Reference： [1]Patent: EP1498410,2005,A1 .Location in patent: Page/Page column 9-10

21
[ 64-17-5 ]
[ 56-41-7 ]
[ 98-66-8 ]
L-alanine ethyl ester 4-chlorobenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63.2%		Example 7. L-alanine (1.50 g, 16.84 mmol) and 4-chlorobenzenesulfonic acid (4-CBS) (3.89 g, 20.20 mmol) were added to ethanol (15 ml) and the mixture was heated overnight at 70 C to perform esterification. To complete the esterification reaction, the mixture was heated to 90 C and ethanol (200 ml) was added over 3.5 hr while distilling away almost the same amount of ethanol. Thereafter, the solvent was evaporated under reduced pressure and the residue was dried under reduced pressure. Ethanol (1 ml) and diethyl ether (60 ml) were added to partially crystallize an oily residue and' the mixture was stirred at room temperature to give a slurry. This slurry was cooled overnight in a refrigerator and the crystals were separated and dried to give 3.52 g of L-alanine ethyl ester <strong>[98-66-8]4-chlorobenzenesulfonate</strong> (L-Ala-OEt 4-CBS salt) dry crystals (L-Ala-OEt 4-CBS salt content 93.6%, 10.64 mmol, yield 63.2%).

Reference： [1]Patent: EP1541546,2005,A1 .Location in patent: Page/Page column 8

22
2-{4-[N-(1-hydroxy-2-methylprop-2-yl)sulphamoyl]anilino}-4-(1,2-dimethylimidazol-5-yl)pyrimidine [ No CAS ]
[ 98-66-8 ]
[ 602306-70-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	With pyridine; at 0 - 20℃; for 18.1667h;	2- {4-[N-(1-Hydroxy-2-methylprop-2-yl) sulphamoyl] anilino}-4-(1, 2-dimethylimidazol- 5-yl) pyrimidine (Example 59 ; 2.36g, 5.66mmol) was dissolved in dry pyridine (55ml) and the solution stirred and cooled to 0 C under inert gas. Solid p-toluenesulphonyl chloride (5.61g, 29. 4mmol) was added portionwise over 2 minutes. The reaction was stirred at 0 C for 10 minutes and then at room temperature for 18hr. The reaction mixture was diluted with water (200ml) and the precipitated oil allowed to settle out. The supernatant water layer was decanted off and the residual oil was washed with more water and this was decanted off. This process was repeated and then the oil partitioned between EtOAc (100ml) and water (50ml). The layers were separated and the organic layer washed with water (50ml), dried and the solvent evaporated in vacuo to yield the title compound as a gum (1.94g, 60%) NMR 1.0 (s, 6H), 2.36 (s, 3H), 2.38 (s, 3H), 3.77 (s, 2H), 3.93 (s, 3H), 7.20 (d, 1H), 7.43 (d, 2H), 7.55 (s, 1H), 7.65 (m, 5H), 7.87 (d, 2H), 8.45 (d, 1H), 9.9 (s, 1H) ; m/z 571.

Reference： [1]Patent: WO2003/76436,2003,A1 .Location in patent: Page/Page column 71

23
[ 98-66-8 ]
[ 60962-92-7 ]
N-{3,5-Dichloro-4-[3-(4-chloro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-oxamic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate;	Step A A mixture of 2',6'-dichloro-4-methoxy-4'-nitrodiphenyl ether (250 mg, 0.80 mmol), p-chlorobenzene sulfonic acid (90%, 290 mg, 1.4 mmol) and Eaton's reagent was stirred at 80 C. for 5 h and cooled to RT. The reaction mixture was quenched by adding dropwise into 30 mL of ice water. A white precipitate formed. The precipitate was collected by filtration and taken up in CH2Cl2, dried and concentrated. The product was purified by preparative TLC (25% EtOAc in Hex). NMR (400 MHz, CDCl3) d 8.29-8.30 (s, 2H), 7.83-7.86 (d, 2H), 7.53-754 (d, 1H), 7.42-7.46 (d, 2H), 7.04-7.07 (dd, 1H), 6.82-6.87 (d, 1H), 3.73 (s, 3H). MS Calc.: 486.9, Found: 486.0 (M-1).
	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate;	Step A A mixture of 2',6'-dichloro-4-methoxy-4'-nitrodiphenyl ether (250 mg, 0.80 mmol), p-chlorobenzene sulfonic acid (90%, 290 mg, 1.4 mmol) and Eaton's reagent was stirred at 80 C. for 5 h and cooled to RT. The reaction mixture was quenched by adding dropwise into 30 mL of ice water. A white precipitate formed. The precipitate was collected by filtration and taken up in CH2Cl2, dried and concentrated. The product was purified by preparative TLC (25% EtOAc in Hex). NMR (400 MHz, CDCl3) d 8.29-8.30 (s, 2H), 7.83-7.86 (d, 2H), 7.53-7.54 (d, 1H), 7.42-7.46 (d, 2H), 7.04-7.07 (dd, 1H), 6.82-6.87 (d, 1H), 3.73 (s, 3H). MS Calc.: 486.9, Found: 486.0 (M-1).

Reference： [1]Patent: US2003/114521,2003,A1
[2]Patent: US6326398,2001,B1

24
triisopentyl-phosphine sulfide [ No CAS ]
[ 98-66-8 ]
[ 23079-28-9 ]

Yield	Reaction Conditions	Operation in experiment
	In chlorobenzene;	EXAMPLE 9 Preparation of triisoamylphosphine oxide 4.1 g (15 mmol) of triisoamylphosphine sulfide in 70 ml of chlorobenzene (b.p.=132 C.) are combined with 34.7 g (0.18 mol) of p-chlorobenzenesulfonic acid and then heated for 8 hours at reflux. After cooling to room temperature, the reaction mixture is extracted several times with 80 ml portions of ice water and then the chlorobenzene solution is washed with sodium bicarbonate solution. The solution is dried over sodium sulfate and the chlorobenzene is removed in vacuum. Yield: 3 g of solid identified by mass spectroscopy as triisoamylphosphine oxide.

Reference： [1]Patent: US4745224,1988,A

25
12-tungstosilicic acid (H₄ SiW₁₂ O_40.24H₂ O) [ No CAS ]
[ 98-66-8 ]
dichlorodiphenyl sulfone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In chlorobenzene;	EXAMPLE 10 A 193 g (1.0 mole) quantity of p-chlorobenzenesulfonic acid, 169 g (1.5 moles) of chlorobenzene and 10 g of 12-tungstosilicic acid (H4 SiW12 O40.24H2 O) were refluxed with heating and stirring. The reaction system was kept at the reflux temperature for 20 hours, while refluxing the chlorobenzene and removing the produced water by subjecting the azeotropic mixture with the chlorobenzene to phase separation. The reaction mixture was cooled and the catalyst was separated by filtration. After the mother liquor was washed with water, the chlorobenzene was distilled off under reduced pressure, giving 267 g of dichlorodiphenylsulfone in a yield of 93% (melting point 145 to 148 C.).

Reference： [1]Patent: US4778932,1988,A

26
[ 98-66-8 ]
[ 76917-15-2 ]
[ 80519-87-5 ]

Yield	Reaction Conditions	Operation in experiment
75.3%		EXAMPLE 11 A 1.2 g quantity of 1-diazo-2-undecanone is dissolved in 50 ml of ether, and 1.6 g of p-chlorobenzenesulfonic acid is slowly added to the solution at room temperature. The mixture is stirred until no nitrogen is evolved. The reaction mixture is washed with water, and the ethereal layer is dried over anhydrous sodium sulfate and distilled in a vacuum to remove the solvent. The residue is recrystallized from ether/petroleum ether to give 1.62 g of 2-oxoundecyl-p-chlorobenzene sulfonate (Compound 68), m.p. 51 to 51.5 C. Yield 75.3%. MS (M+): 360

Reference： [1]Patent: US4411911,1983,A

27
[ 98-66-8 ]
[ 5003-71-4 ]
[3-(7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]carbamic acid tert-butyl ester 4-chlorobenzenesulfonic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%		Example 12 r3-r7-Benzyl-9-oxa-3.7-diazabicvclor3.3.11non-3-yl*)rhoropyl1carbamic acid tert- butyl ester. 4-chlorobenzenesulfonic acid saltTo 3-bromopropylamine hydrobromide (139.32 g, 636.40 mmol) was added a solution of di-tert-butyl dicarbonate (112.46 g, 510.13 mmol) in MIBK (800 mL) and 2.5 M sodium hydroxide (310 mL). The resulting mixture was stirred for 1 hour at room temperature. The reaction was monitored by TLC (9:1 isohexane: ethyl acetate, potassium permanganate stain). Water (345 mL) was added and the mixture stirred for 10 minutes. The phases were separated and the lower (aqueous) phase discarded. To the retained organic phase was added 3-benzyl-9- oxa-3,7-diazabicyclo[3.3.1]nonane dihydrochloride (148.43 g, 509.68 mmol; see Preparation O above) and 2.5 M sodium hydroxide (660 mL). This mixture was heated at 650C for 7 hours. At 65C, the phases were separated and the lower (aqueous) phase discarded. The organic phase was re-heated to 65C and extracted with 10% w/w aqueous citric acid (562 mL). The phases were separated and the upper (organic) phase discarded. To the resulting aqueous phase was added MIBK (800 mL) and 5 M sodium hydroxide (230 mL) containing approximately 10% w/v sodium chloride (22.84 g). The resulting mixture was stirred at room temperature for 15 minutes. The phases were separated and the lower (aqueous) phase discarded. The organic phase was azeo-dried by removal of solvent (300 mL) by distillation under reduced pressure (keeping the temperature below 7O0C). The mixture was clarified by filtration whilst still hot and the residue washed with MIBK (115 mL). The temperature was adjusted to 6O0C and a solution of purified (see J. Am. Pharm. Assoc. 239-241 (1949)) 4-chlorobenzenesulfonic acid (99.24 g, 515.20 mmol) in MIBK (225 mL) was added over 90 minutes. The reaction mixture was then cooled to room temperature causing the product to crystallize from solution. The mixture was cooled to 5C, the product was collected by filtration and the cake washed with MIBK (225 mL). The product was dried as far as possible on the filter, then oven dried in vacuo (50C, 24 h) to give the title compound as a white solid (257.44 g, 453.13 mmol,%).1H NMR (300 MHz, DMSOd6): delta 7.61 (d, J= 8.7 Hz, 2H)5 7.46 - 7.35 (m, 7H), 7.10 (t, J= 5.7 Hz, IH), 4.15 (s, 2H), 3.70 (s, 2H), 3.40 (d, J= 12.1 Hz, 3H), 3.07 EPO <DP n="131"/>(d, J= 11.9 Hz, 4H)5 2.97 (q, J= 6.3 Hz, 2H), 2.84 (t, J= 7.1 Hz, 2H), 2.76 (d, J=11.9 Hz, 2H), 1.70 (quintet, J= 6.7 Hz, 2H), 1.45 (s, 9H).

Reference： [1]Patent: WO2006/135316,2006,A1 .Location in patent: Page/Page column 129-130

28
[3-(7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]carbamic acid tert-butyl ester [ No CAS ]
[ 98-66-8 ]
[3-(7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]carbamic acid tert-butyl ester, 4-chlorobenzenesulfonic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In MIBK (methyl isobutyl ketone); at 60℃; for 1.5h;	To 3-bromopropylamine hydrobromide (139.32 g, 636.40 mmol) was added a solution of di-tert-butyl dicarbonate (112.46 g, 510.13 mmol) in MIBK (800 mL) and 2.5 M sodium hydroxide (310 mL). The resulting mixture was stirred for 1 hour at room temperature. The reaction was monitored by TLC (9:1 isohexane: ethyl acetate, potassium permanganate stain). Water (345 mL) was added and the mixture stirred for 10 minutes. The phases were separated and the lower (aqueous) phase discarded. To the retained organic phase was added 3-benzyl-9- oxa-3,7-diazabicyclo[3.3.1]nonane dihydrochloride (148.43 g, 509.68 mmol; .; see WO 02/083690) and 2.5 M sodium hydroxide (660 mL). This mixture was heated at 65C for 7 hours. At 650C, the phases were separated and the lower (aqueous) phase discarded. The organic phase was re-heated to 650C and extracted with 10% w/w aqueous citric acid (562 mL). The phases were separated and the upper (organic) phase discarded. To the resulting aqueous phase was added MIBK (800 mL) and 5 M sodium hydroxide (230 mL) containing approximately 10% w/v EPO <DP n="41"/>sodium chloride (22.84 g). The resulting mixture was stirred at room temperature for 15 minutes. The phases were separated and the lower (aqueous) phase discarded. The organic phase was azeo-dried by removal of solvent (300 mL) by distillation under reduced pressure (keeping the temperature below 7O0C). The mixture was clarified by filtration whilst still hot and the residue washed with MIBK (115 mL). The temperature was adjusted to 6O0C and a solution of purified (see J. Am. Pharm. Assoc. 239-241 (1949)) 4-chlorobenzenesulfonic acid (99.24 g, 515.20 mrnol) in MIBK (225 mL) was added over 90 minutes. The reaction mixture was then cooled to room temperature causing the product to crystallize from solution. The mixture was cooled to 5C, the product was collected by filtration and the cake washed with MIBK (225 mL). The product was dried as far as possible on the filter, then oven dried in vacuo (50C, 24 h) to give the title compound as a white solid (257.44 g, 453.13 mmol, 89%). 1H NMR (300 MHz, DMSO-d6) delta 7.61 (d, J= 8.7 Hz, 2H), 7.46 - 7.35 (m, 7H), 7.10 (t, J= 5.7 Hz, IH), 4.15 (s, 2H), 3.70 (s, 2H), 3.40 (d, J= 12.1 Hz, 3H), 3.07 (d, J= 11.9 Hz, 4H), 2.97 (q, J= 6.3 Hz, 2H), 2.84 (t, J= 7.1 Hz, 2H), 2.76 (d, J= 11.9 Hz, 2H), 1.70 (quintet, J= 6.7 Hz, 2H), 1.45 (s, 9H).

Reference： [1]Patent: WO2006/137770,2006,A1 .Location in patent: Page/Page column 38-39

29
10-phenylphenothiabismine 5,5-dioxide [ No CAS ]
[ 98-66-8 ]
[ 2437-33-4 ]

Reference： [1]Heterocycles,2007,vol. 74,p. 771 - 790

30
[ 106-54-7 ]
[ 98-66-8 ]

Reference： [1]Synthesis,2012,vol. 2012,p. 316 - 322
[2]Tetrahedron Letters,2008,vol. 49,p. 3291 - 3293

31
[ 98-66-8 ]
[ 4547-68-6 ]

Yield	Reaction Conditions	Operation in experiment
98%		General procedure: To a solution of CCA(0.1548 g, 0.6 mmol) in tetrahydrofuran (3-5 mL), PPh3 (0.5246 g, 2 mmol)was added at 0-5C with stirring. A white suspension was formed to which p-toluenesulfonic acid (0.1720 g, 1 mmol) was added and stirring continued for 15 min. NaN3 (0.065 g, 1 mmol) was added and the temperature was raised up to room temperature. Stirring was continued for 1 min at room temperature. After completion of the reaction (TLC), the reaction mixture was concentrated, washed with EtOAc (4-6 mL), and cold distilled water (5 mL). The organic layer was dried with anhydrous Na2SO4, passed through a short silica-gel column using n-hexane/ethylacetate (10/1) as eluent. p-Toluenesulfonyl azide was obtained with 98% yield after removing the solvent under reduced pressure.

Reference： [1]Journal of Sulfur Chemistry,2014,vol. 35,p. 119 - 127
[2]Synlett,2008,p. 2885 - 2887

32
[ 98-66-8 ]
[ 637-87-6 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 5950 - 5953

33
[ 38980-51-7 ]
[ 27886-58-4 ]
[ 98-66-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; at 170℃; for 3h;	Example 11 g (3.5 mmol) of 2,4-dichlorodiphenyl sulfone was suspended in 10 ml (18.4 g corresponding to 180 mmol) of concentrated sulfuric acid (96% by weight), and stirred at 170 C. for 3 h.After a reaction time of 3 h, no dichlorodiphenyl sulfone, nor any monochlorobenzene, was present in the reaction discharge. According to HPLC analysis, the reaction product comprised a mixture of 2-, 3- and 4-chlorobenzenesulfonic acid. Instead of an isomerization, exclusively the splitting products of dichlorodiphenyl sulfone were obtained. An isomerization of dichlorodiphenyl sulfone is not possible in this way.

Reference： [1]Patent: US2011/218357,2011,A1 .Location in patent: Page/Page column 4

34
[ 1142-19-4 ]
[ 98-66-8 ]

Reference： [1]Synthesis,2012,vol. 2012,p. 316 - 322

35
[ 57103-02-3 ]
[ 98-66-8 ]
[ 551951-03-2 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 3382 - 3384

36
[ 57103-02-3 ]
[ 98-66-8 ]
[ 551951-18-9 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 3382 - 3384

37
[ 98-66-8 ]
[ 99685-96-8 ]
[ 1373042-68-2 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2176 - 2179

38
[ 98-66-8 ]
calcium 4-chlorobenzenesulfonate [ No CAS ]

Reference： [1]Green Chemistry,2012,vol. 14,p. 2129 - 2132

39
[ 98-66-8 ]
[Co(phen)₂CO₃]Cl*5H₂O [ No CAS ]
[Co(phen)₂CO₃](4-chlorobenzenesulphonate)*3H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydroxide; In water; at 20℃;	[Co(phen)2CO3]Cl?5H2O (0.2 g, 0.33 mmol) was dissolved in 5 mL of water and to this, 5 mL aqueous solution of 0.063 g (0.33 mmol) 4-chlorobenzenesulphonic acid and 0.013 g (0.33 mmol) sodium hydroxide was added. When the resultant solution was allowed to evaporate slowly at room temperature, reddish-pink coloured crystals started appearing next day, which were collected and dried in air (yield 75%). The complex salt decomposed at 210 C. Anal. Calcd. for C31H26CoClN4O9S: C, 51.31; H, 3.59; N, 7.72; Co, 8.14. Found (%): C, 51.03; H, 3.40; N, 7.50; Co, 7.96. IR/cm-1 (KBr pellet, b = broad, s = strong, m = medium, w = weak): 3440(b), 3057(w), 1657(s), 1633(s), 1517(m), 1427(s), 1341(w), 1223(m), 1190(s), 1120(w), 1004(s), 856(s), 752(s), 719(s), 647(s), 562(w), 482(m). 1H NMR/ppm (DMSO-d6): cation, [Co(phen)2CO3]+, delta = 9.25(d, H9), 9.20(d, H7), 8.91(d, H2), 8.89-8.40(m, H8/6/5), 7.83-7.75(m, H3/4); anion [C6H4SO3Cl]- delta = 7.57(d, H2/6), 7.35(d, H3/5). 13C NMR/ppm (DMSO-d6): delta = 163.14, 154.11, 151.66, 147.31, 147.04, 146.82, 140.83, 139.82, 139.73, 132.88, 130.31, 130.16, 128.12, 127.99, 127.79, 127.66, 127.49, 127.45, 126.85. Solubility (H2O, 25 C) = 0.205 g/100 mL, Ksp = 8.0 × 10-6. UV/Vis (lambdamax, H2O): 509, 351, 272 and 224 nm.

Reference： [1]Journal of Molecular Structure,2013,vol. 1033,p. 208 - 214

40
[ 40015-10-9 ]
[ 98-66-8 ]
[ 1440957-38-9 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 906 - 910
Angew. Chem.,2012,vol. 125,p. 940 - 944,5

41
[ 108-90-7 ]
[ 80-07-9 ]
[ 98-66-8 ]
[ 38980-51-7 ]

Yield	Reaction Conditions	Operation in experiment
67%Chromat.	With sulfur trioxide; at 75℃; for 2h;Inert atmosphere;	The MCB produced in example 8 was washed with the same volume of 0.02 % aq. potassium hydroxide solution, then washed again with 3 times the same volume of deionized water. The final moisture content of the MCB was approx. 1000 ppm by weight as measured by Karl-Fisher titration. In a dry 3 -neck 250-mL round bottom flask, containing a PTFE-coated stir bar and fitted with a thermocouple, a distillation receiver allowing returning the vapors to the mixture (Barrett trap) + reflux condenser + H2SO4 scrubber, and a inlet tube connected to an oleum distillation set up and a nitrogen inlet, was introduced under nitrogen 90.06 g of MCB from example 8 neutralized as detailed above (0.80 mol). The flask was then sealed and the mixture was heated to 75C under agitation. When the mixture had reached 75C, 55.00 g of SO3 vapors (0.14 mol) were slowly introduced to the reactor from an adjacent oleum distillation set up. The addition lasted 60 minutes, during which the temperature was maintained at 75C by applying external cooling to the reaction flask. At the end of the addition, the reaction mixture was held at 75C for 1 hour. At the end of the reaction, the mixture was analyzed by GC and found to contain : ? 61 wt % chlorobenzenesulfonic acid (0.49 mol, 67 % yield, 95.7 % pCBSA/4.3 % oCBSA) ? 14 wt % DCDPS (0.07 mol, 9 % yield, 90 % / 5.5 % / 3.5 % 4,472,473,4') ? 9 wt H2S04 (0.13 mol, 19 % yield) ? 16 wt % MCB (0.19 mol).

Reference： [1]Patent: WO2013/87594,2013,A1 .Location in patent: Page/Page column 18; 19

42
[ 98-66-8 ]
[ 536-74-3 ]
1-phenylvinyl 4-chlorobenzenesulfonate [ No CAS ]

Reference： [1]ChemCatChem,2013,vol. 5,p. 3005 - 3013
[2]Journal of Catalysis,2018,vol. 365,p. 43 - 54
[3]Green Chemistry,2017,vol. 19,p. 3530 - 3534

43
[ 591-80-0 ]
[ 98-66-8 ]
[ 1604837-57-1 ]

Reference： [1]Helvetica Chimica Acta,2014,vol. 97,p. 137 - 145

44
[ 1575-74-2 ]
[ 98-66-8 ]
[ 1604837-58-2 ]

Reference： [1]Helvetica Chimica Acta,2014,vol. 97,p. 137 - 145

45
[ 75371-78-7 ]
[ 98-66-8 ]
(tetrahydro-3-methyl-5-oxofuran-2-yl)methyl 4-chlorobenzenesulfonate [ No CAS ]

Reference： [1]Helvetica Chimica Acta,2014,vol. 97,p. 137 - 145

46
[ 13668-61-6 ]
[ 98-66-8 ]
[ 1604837-62-8 ]

Reference： [1]Helvetica Chimica Acta,2014,vol. 97,p. 137 - 145

47
[ 98-66-8 ]
[ 536-74-3 ]
[ 16215-12-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 1861 - 1864

48
[ 928-49-4 ]
[ 98-66-8 ]
6-chloro-3,4-diethylbenzo[c][1,2]oxathiine 1,1-dioxide [ No CAS ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 9776 - 9778

49
[ 98-66-8 ]
[ 140-88-5 ]
(E)-4-chloro-2-(3-ethoxy-3-oxoprop-1-en-1-yl)benzenesulfonic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 15248 - 15251

50
[ 319460-85-0 ]
[ 98-66-8 ]
axitinib 4-chlorobenzenesulphonic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	In isopropyl alcohol; at 20 - 50℃;	Example 2 Preparation of salt of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethanyl]- indazole and 4-chlorobenzenesulphonic acid 250 mg (0.647 mmol) of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethanyl]- indazole was dissolved in 5 mL of 2-propanol by heating to 50C. 125 mg (0.649 mmol) of 4- chlorobenzenesulphonic acid was dissolved in 0.5 mL of 2-propanol at room temperature and the solution of the counterion was drop-wise added to the solution of the API of 50C.The solution at 50C is stirred for 1 hour in closed vial, cooled back to room temperature and stirred overnight the resulting suspension was filtered off and dried at laboratory condition. Yield: 277 mg (74%)1H-NMR analysis showed a 1:1 stoichiometry of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E- [2-(pyridin-2-yl)ethanyl]indazoleand 4-chlorobenzenesulphonic acid.

Reference： [1]Patent: WO2015/67224,2015,A1 .Location in patent: Page/Page column 17

51
[ 98-66-8 ]
[ 109-73-9 ]
[ 6419-73-4 ]

Yield	Reaction Conditions	Operation in experiment
92%		General procedure: To a cold solution of PPh3 (0.327 g, 1.25 mmol) in CH2Cl2 (3 mL), freshly preparedNCBT (0.188 g, 1.25 mmol) was added with continuous stirring. p-Toluenesulfonic acid(0.172 g, 1 mmol)was then added and stirringwas continued for 15min at room temperature.Benzylamine (0.267 g, 2.5 mmol) was added. The white suspension was neutralized by triethylamine (0.139 mL). Stirring was continued for 80 min at room temperature. Theprogress of the reaction was followed by TLC. Upon completion of the reaction, theconcentrated residue was passed through a short silica-gel column using n-hexane-ethylacetate (3:1) as eluent. N-Benzyl-4-methylbenzenesulfonamide was obtained with 90%(0.236 g) yield after removing the solvent under reduced pressure

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2015,vol. 190,p. 1703 - 1714

52
[ 109-99-9 ]
[ 103-30-0 ]
[ 98-66-8 ]
4-(2-bromo-1,2-diphenylethoxy)butyl 4-chlorobenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-Bromosuccinimide; at 25℃; for 24h;Inert atmosphere;	General procedure: Sulfonic acid 2a-2i (0.101 mmol, 1.01 Equiv.) was addedto the solution of olefin 1a-1k (0.10 mmol, 1. Equiv.) and NXS (0.20mmol, 0.20 Equiv.) in respective cyclicether (3 mL). The reaction mixture was stirred for 24 to 36 h at roomtemperature. The solvent was then removed under reduce pressure and residue waspurified by flash column chromatography (gradient elution, EtOAc : n-hexane; 1:100 V/V, 50 mL; 1:20, V/V400 mL), to yield the corresponding products

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 5743 - 5746

53
[ 98-66-8 ]
C₁₅H₁₇NO [ No CAS ]
C₂₁H₂₀ClNO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With palladium diacetate; N-fluorobis(benzenesulfon)imide; In 1,2-dichloro-ethane; at 90℃; for 7h;Inert atmosphere; Glovebox;	General procedure: A 4 ml vial was charged with Pd(OAc)2 (3.5 mg, 0.015 mmol, 0.1 equiv.), p-toluenesulfonic acid (56.8 mg, 0.33 mmol, 2.2 equiv.), NFSI (95 mg, 0.3 mmol,2.0 equiv.), DCE (2.2 ml) and oxime substrate 2a (34.2 mg, 0.15 mmol, 1.0 equiv.).The vial was sealed with a polytetrafluoroethylene-lined cap and transferred into aglove box. The vial was opened and purged under a N2 atmosphere for five minutes.The vial was then sealed again and heated in a pie block at 90 C for seven hours under stirring. After being cooled to room temperature (r.t.), Na2CO3 (150 mg) and 1,10-phenanthroline (5.1 mg) were added to quench the reaction, and the mixture was further stirred at r.t. for 36 hours. The mixture was filtered through a small plugof Celite to remove the precipitate and washed with dichloromethane. The solvent was then removed in vacuo and the residue was further purified by flash chromatography. Product 3a was obtained as a yellowish oil (40.7 mg, 68%). The procedure to prepare compound 3a is generally representative for all the products shown in Table 2. Any deviations from this protocol are specified in the footnotes ofTable 2 and in the Supplementary Information.

Reference： [1]Nature Chemistry,2015,vol. 7,p. 829 - 834

54
[ 98-66-8 ]
[ 530-62-1 ]
C₉H₇ClN₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetonitrile; at 20℃; for 0.00833333h;Sonication;	General procedure: In a 100 mL round-bottom flask, benzoic acid 1 (0.122 g= 1 mmol) / benzene sulfonic acid 18 (0.152 g = 1 mmol),and triethylamine (0.1 ml = 1.2 mmol) in acetonitrile (10mL) were taken. 1,1-carbonyldiimidazole (0.162 g = 1mmol) was added to the above-mentioned mixture and reflux for 15 to 30 min. Acyl imidazole formation was confirmedby TLC monitoring. Then, hydrazine hydrate 55% (SigmaAldrich) (1 mL) was added into the reaction mixture andfurther reflux for 2-4 h. After completion (TLC monitoring), the reaction mixture was poured onto crushed ice, formed precipitates were filtered and washed with plenty of distilled water and then with hexane. The crude products were recrystallized from ethyl acetate and hexane.

Reference： [1]Letters in Organic Chemistry,2015,vol. 12,p. 637 - 644

55
vismodegib [ No CAS ]
[ 98-66-8 ]
C₁₉H₁₄Cl₂N₂O₃S*C₆H₅ClO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 50℃; for 1h;	100 mg (0.237 m mol) of 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide was dissolved in 4 mL of acetonitrile by heating to 50C. 45.7 mg(0.237 mmol) of 4-chlorobenzenesulphonic acid was dissolved in 0.5 mL of acetonitrile atroom temperature and the solution of the counterion was drop-wise added to the solution ofthe API of 50C.The solution at 50C is stirred for 1 hour in closed vial, cooled back to room temperature and stirred overnight. The solvent was evaporated completely by rotary evaporation and then 2 mL of methyl tert-butyl ether was added and stirred at room temperature for 5 hours. Theresulting suspension was filtered off and dried at laboratory conditions.1H-N MR analysis showed a 1:1 stoichiometry of 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamideand 4-chlorobenzenesulphonic acid.This salt was characterized by Raman spectroscopy (Fig. 20), 1H-NMR (Fig. 21), XRPD (Fig. 22), and by DSC technique (Fig. 23).

Reference： [1]Patent: WO2015/169269,2015,A1 .Location in patent: Page/Page column 18

56
[ 941678-49-5 ]
[ 98-66-8 ]
(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile4-chlorobenzenesulphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	In methanol; at 50℃; for 1h;	200 mg (0.653 mmol) of (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-l- yllpropanenitrile was dissolved in 8 mL of methanol by heating to 50C applying a continuous agitation. 125.7 mg (0.653 mmol) of 4-chlorobenzenesulphonic acid was dissolved in 2 mL of methanol at room temperature. The methanol solution of 4-chlorobenzenesulphonic acid was drop-wise added to the solution of (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2f3-d]pyrimidin-4-yl)pyrazol-l- yl]propanenitrile at 50eC, agitated for additional 60 minutes at 50C and then cooled back to room temperature. The suspensions was stirred at room temperature overnight and then filtered and dried with vacuum suction. Product: 235 mg; yield: 72% HPLC purity: 99.0% The sligthly yellowish powder obtained was analyzed by FTIR spectroscopy. Similarly, the same result was obtained using any of the recrystallization solvents listed in the Table 3.

Reference： [1]Patent: WO2016/74650,2016,A1 .Location in patent: Page/Page column 22-23

57
[ 609-14-3 ]
[ 98-66-8 ]
ethyl 2-[(4-chlorophenyl)sulfonyl]oxy}-2-methyl-3-oxobutanoate [ No CAS ]
ethyl 2-[(4-chlorophenyl)sulfonyl]oxy}-2-methyl-3-oxobutanoate [ No CAS ]