13659-23-9|2-Bromo-5-chlorophenol| Ambeed

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Quality Control of [ 13659-23-9 ] Purity: 97% SDS Specification

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Product Details of [ 13659-23-9 ]

CAS No. :	13659-23-9
Formula :	C₆H₄BrClO
M.W :	207.45
SMILES Code :	BrC1=C(C=C(C=C1)Cl)O
MDL No. :	MFCD00142870
InChI Key :	FMRKYXVZQWHGDA-UHFFFAOYSA-N
Pubchem ID :	13284272

Safety of [ 13659-23-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 13659-23-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	41.18
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	20.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.01
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.16
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.81
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.84
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.7
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.7

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.61
Solubility	0.0509 mg/ml ; 0.000245 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.26
Solubility	0.115 mg/ml ; 0.000556 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.3
Solubility	0.105 mg/ml ; 0.000506 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.32 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.45

Application In Synthesis of [ 13659-23-9 ]

* 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.

Downstream synthetic route of [ 13659-23-9 ]

[ 13659-23-9 ] Synthesis Path-Downstream 1~35

1
[ 1193-72-2 ]
[ 124-41-4 ]
[ 13659-23-9 ]
[ 120-83-2 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1932,vol. 51,p. 98,109.
[2]Recueil des Travaux Chimiques des Pays-Bas,1932,vol. 51,p. 98,109.

2
[ 823-57-4 ]
[ 13659-23-9 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1932,vol. 51,p. 98,109.

3
[ 13659-23-9 ]
benzoic acid-(2-bromo-5-chloro-phenyl ester) [ No CAS ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1932,vol. 51,p. 98,109.

4
[ 108-43-0 ]
[ 40979-03-1 ]
[ 13659-23-9 ]
[ 13631-21-5 ]
[ 855836-62-3 ]

References: [1]Journal of Organic Chemistry,1997,vol. 62,p. 4504 - 4506.
[2]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

5
[ 108-43-0 ]
[ 89284-48-0 ]
[ 13659-23-9 ]
[ 13631-21-5 ]
[ 855836-62-3 ]

References: [1]Journal of Organic Chemistry,1997,vol. 62,p. 4504 - 4506.
[2]Journal of Organic Chemistry,1997,vol. 62,p. 4504 - 4506.
[3]Journal of Organic Chemistry,1997,vol. 62,p. 4504 - 4506.
[4]Tetrahedron,2007,vol. 63,p. 4959 - 4967.
[5]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

6
[ 13659-23-9 ]
[ 74-88-4 ]
[ 174913-09-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; In N,N-dimethyl-formamide; for 2h;	Preparation Example 27 Synthesis of 1-bromo-4-chloro-3-(4-ethoxybenzyl)-6-methoxybenzene; A suspension of <strong>[13659-23-9]2-bromo-5-chlorophenol</strong> (2.85 g, 13.7 mmol; synthesized in reference to International Patent Publication WO0109122), potassium carbonate (1.89 g, 13.7 mmol), n-BU4NI (50 mg, 0.137 mmol), methyl iodide (1.28 mL, 20.6 mmol) and N,N-dimethylformamide (8.0 mL) was stirred for two hours. An iced water was added and the obtained mixture was extracted with ethyl acetate twice. The combined organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=95:5) to obtain colorless oily 2-bromo-5-chloroanisole (2.94 g, 97%). Then, oxalyl chloride (1.23 mL, 15.1 mmol) and N,N-dimethylformamide (2 drops) were added to 4-ethoxybenzoic acid (2.28 g, 13.7 mmol) in chloroform (8 mL) and stirred for five hours. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (5 mL). To this solution, a chloroform solution (10 mL) of 2-bromo-5-chloroanisole (2.94 g, 13.3 mmol) was added and then aluminum chloride (2.07 g, 15.5 mmol) was added portion wise at -10C over five minutes. After stirred at 5C for one hour, the reaction mixture was to room temperature and stirred for 13 hours. The reaction mixture was poured into an iced water and extracted with chloroform three times. After washed with 1 M hydrochloric acid, water, brine, the combined organic layer was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by NH type silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain (5-bromo-2-chloro-6-methoxyphenyl)(4-ethoxyphenyl)methanone (1.53 g, 31%) as a colorless crystal. Then, Et3SiH (1.62 mL, 10.1 mmol) and BF3·Et2O (0.772 mL, 6.09 mmol) were added sequentially to a chloroform - acetonitrile (1:1; 16 mL) solution of (5-bromo-2-chloro-6-methoxyphenyl)(4-ethoxyphenyl)methanone (1.50 g, 4.06 mmol) at -5C. The reaction mixture was warmed to room temperature and stirred for 16 hours. After the reaction mixture was added with a saturated sodium carbonate aqueous solution and extracted with chloroform, the organic layer was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain a colorless oily title compound (1.48 g, 99%). 1H NMR (200 MHz, CHLOROFORM-d) delta ppm 1.40 (t, J=7.0 Hz, 3 H) 3.87 (s, 3 H) 3.93 (s, 2 H) 4.01 (q, J=7.0 Hz, 2 H) 6.77 - 6.87 (m, 2 H) 6.90 (s, 1 H) 7.03 - 7.12 (m, 2 H) 7.29 (s, 1 H). EI 354(M+), 356(M+2), 358(M+4).

References: [1]Patent: EP1845095,2007,A1 .Location in patent: Page/Page column 41-42.
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 3247 - 3261.

7
[ 174913-09-8 ]
[ 13659-23-9 ]

Yield	Reaction Conditions	Operation in experiment
32%	With boron tribromide; In dichloromethane; at -40 - 20℃; for 12.33h;	To a solution of 1-bromo-5-chloro-2 methoxyphenyl 275 (2.5 g, 11 mmol, 1 eq) in DCM (100 mL) was added dropwise BBr3 (1 M solution in DCM, 38.5 mmol, 3.5 eq) over 20 min at -40 C. The solution was warmed to rt and stirred for 12 h. TLC (3:2 Hexane:DCM) showed complete consumption of 275. The solution was quenched with NaHCO3 and stirred until two phases appeared. The organic was separated, washed with brine, dried, filtered and concentrated in vacuo to afford 0.80 g of 276 as a white solid which was used without purification. Yield 32%
		2-Bromo-5-chloroanisole (461 mg, 2.08 mmol) was dissolved in anhydrous dichloromethane (5 mL) and cooled to 0 C. To the cooled solution was added boron tribromide solution (1M in dichloromethane, 2 eq). The reaction mixture was stirred at 0 C. for 5 minutes, warmed to room temperature and stirred at room temperature for 2 hours. The reaction mixture was then poured into ice-water and extracted with ethyl acetate (3×). The combined organic layer was then dried over sodium sulfate, filtered and concentrated to get the crude phenol which was used in the next step without further purification.

References: [1]Patent: US2008/114167,2008,A1 .Location in patent: Page/Page column 208.
[2]Patent: US2007/265332,2007,A1 .Location in patent: Page/Page column 20.

8
[ 13659-23-9 ]
[ 1895-39-2 ]
[ 1056942-37-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With caesium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 4h;	To a solution of <strong>[13659-23-9]2-bromo-5-chlorophenol</strong> (1 g, 4.8 mmol) in DMF/water (45 mL/5 mL) was added sodium chlorodifluoroacetate (1.95 g, 12.0 mmol) and cesium carbonate (3.14 g, 9.64 mmol), and the reaction mixture was heated to 100 C. for 4 hours. The reaction mixture was cooled and diluted with TBME (20 mL) and water (20 mL). The organic layer was collected, washed with saturated aqueous NaHCO3 solution, brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound (1.21 g, 98%), which was used without further purification.
	With caesium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 3h;	Sodium chlorodifluoroacetate (2.5 eq.) and cesium carbonate (1.5 eq.) were added to a solution of <strong>[13659-23-9]2-bromo-5-chlorophenol</strong> in DMF containing 10 volume % water, and the reaction mixture was heated for 3h at 100 C. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water (3×), then with brine (1×). The organic layer was dried over sodium sulfate and concentrated to obtain the crude product which was used in the next step without further purification.
	With caesium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 16h;	To a solution of <strong>[13659-23-9]2-bromo-5-chlorophenol</strong> (4.34 g, 20.92 mmol, Ark Pharm) in N,N-dimethylformamide (21.79 ml, 20.92 mmol) was added sodium chlorodifluoroacetate (7.34 g, 48.1 mmol), cesium carbonate (9.54 g, 29.3 mmol), and water (2.179 ml, 20.92 mmol). The reaction was heated at 100 C for 16 h. After 16 h, the reaction was partitioned between EtOAc (100 mL) and water (50 mL). The aqueous layer was extracted with EtOAc (2x70mL). The organic portions were combined and washed with water (2x50 mL), 10% aq citric acid (1x30 mL), and brine, dried over MgS04, filtered, and concentrated to provide 1- bromo-4-chloro-2-(difluoromethoxy)benzene (4.35 g, 16.90 mmol, 81 % yield) as a colorless oil. The material was used without further purification.

References: [1]Patent: US2014/315878,2014,A1 .Location in patent: Paragraph 0493; 0494.
[2]Patent: US2007/265332,2007,A1 .Location in patent: Page/Page column 20.
[3]Patent: WO2013/122897,2013,A1 .Location in patent: Page/Page column 248; 249.

9
[ 108-43-0 ]
[ 13659-23-9 ]
[ 13631-21-5 ]
[ 855836-62-3 ]

References: [1]Tetrahedron,2007,vol. 63,p. 4959 - 4967.
[2]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

10
[ 108-43-0 ]
[ 13659-23-9 ]
[ 13631-21-5 ]

References: [1]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

11
[ 108-43-0 ]
[ 13659-23-9 ]
[ 13631-21-5 ]
[ 855839-02-0 ]

References: [1]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

12
[ 108-43-0 ]
[ 89284-48-0 ]
[ 13659-23-9 ]
[ 13631-21-5 ]
[ 855839-02-0 ]

References: [1]Tetrahedron,2007,vol. 63,p. 4959 - 4967.
[2]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

13
[ 108-43-0 ]
[ 40979-03-1 ]
[ 13659-23-9 ]
[ 13631-21-5 ]
[ 855839-02-0 ]

References: [1]Tetrahedron,2007,vol. 63,p. 4959 - 4967.
[2]Tetrahedron,2007,vol. 63,p. 4959 - 4967.

14
[ 41513-04-6 ]
[ 13659-23-9 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1932,vol. 51,p. 98,109.

15
[ 13659-23-9 ]
[ 100-39-0 ]
[ 690261-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetone; for 3h;Heating / reflux;	A mixture OF 2-BROMO-5-CHLOROPHENOF (3. 93G, 18. 94MMOL), benzyl bromide (3. 42G, 20MMOL) and potassium carbonate (10g, 72. 46MMOL) in acetone (80MUT) was stirred and REFLUXED for 3 hours then cooled, evaporated and dissolved in ETHER/WATER. The organic phase was dried (magnesium sulphate) evaporated and purified by chromatography on silica eluting with ethyl ACETATE/ISO-HEXANE (1: 99) to give 5. 51G of white solid. 1H NMR (CDCL3) delta: 5.13 (2H, s), 6.84 (1H, dd, J=8HZ, 2Hz), 6.93 (1H, d, J=2Hz), 7.34-7. 48 (6H, m).

References: [1]Patent: WO2004/39753,2004,A2 .Location in patent: Page 87-88.

16
[ 108-43-0 ]
[ 13659-23-9 ]

Yield	Reaction Conditions	Operation in experiment
25%	With bromine; In dichloromethane; at 0 - 20℃; for 16h;	A solution of 5.03 gm (39.1 mMol) 3-chlorophenol in 20 mL dichloromethane was cooled in an ice bath as 6.25 gm (39.1 mMol) bromine were added dropwise. The reaction mixture was allowed to warm to room temperature and was stirred for 16 hours. The reaction mixture was diluted with water, the phases separated, and the organic phase dried over magnesium sulfate. The residue was subjected to silica gel chromatography, eluting with 3:2 dichloromethane:hexanes. Fractions containing product were combined and concentrated under reduced pressure to provide 2.04 gm (25%) of 2-bromo-5-chlorophenol. HRMS: Calculated for C4H4OClBr: 205.9134. Found: 205.9125. EA: Calculated for C4H4OClBr: C, 34.74; H, 1.94. Found: C, 34.74; H, 1.76.

References: [1]Patent: EP1204659,2003,B1 .Location in patent: Page/Page column 30.

17
[ 255051-38-8 ]
[ 108-43-0 ]
[ 13659-23-9 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine;	The requisite 4-(4-chloro-2-(R,S)-methylsulfinylphenyl)piperidine was prepared according to the procedures described in Example 2 except 3-chlorophenol was used in place of 3-methoxyphenol. The oxidation of the thiomethyl adduct was carried out according to the procedure described in Example 16, sub-part (e). 3-Chlorophenol (24.28 g) was reacted with bromine (29.78 g) to give 6.15 g of 2-bromo-5-chlorophenol (minor isomer) and 24.60 g 4-bromo-3-chlorophenol (major isomer) after purification by column chromatography (10:1 hexane:EtOAc); minor isomer-1H NMR (CDCl3) delta 7.37 (d, 1H), 7.04 (d, 1H), 6.82 (dd, 1H), 5.55 (s, 1H).

References: [1]Patent: US6365602,2002,B1 .

18
[ 16817-43-9 ]
[ 13659-23-9 ]

Yield	Reaction Conditions	Operation in experiment
	With boron tribromide; In dichloromethane;	9 ml of boron tribromide is added dropwise to a solution containing 20 g of 5-bromo 2-chloro anisole in 200 ml of methylene chloride. Agitation is carried out for 10 minutes at 0 C., then for 24 hours at 20 C. and the reaction medium is poured into a water and ice mixture. The resultant suspension is agitated for 30 minutes, extraction is carried out with methylene chloride, followed by saturation with sodium chloride and extraction twice with methylene chloride. The organic phases are collected, dried over magnesium sulphate, evaporated under reduced pressure and 18.5 g of 5-chloro 2-bromophenol is obtained. M.p.=56 C.

References: [1]Patent: US5985853,1999,A .

19
[ 54537-47-2 ]
[ 13659-23-9 ]
2-(2-Bromo-5-chlorophenoxy)-N,N-dimethylpropionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In 4-methyl-2-pentanone;	EXAMPLE 3 2-(2-Bromo-5-chlorophenoxy)-N,N-dimethylpropionamide (Compound no. 11) <strong>[13659-23-9]2-Bromo-5-chlorophenol</strong> (8 g), 2-bromo-N,N-dimethylpropionamide (6.66 g) and anhydrous potassium carbonate (2.6 g) in methyl iso-butyl ketone (100 ml) were refluxed with stirring overnight. The mixture was cooled to 50 and washed with 5% sodium hydroxide (220 ml) and then water (250 ml). The organic solution was dried and evaporated under reduced pressure to yield a pale red oil, which solidified on cooling. Recrystallisation from 50% aqueous ethanol gave the title compound, m.p. 76-77. Compounds 2, 9, 10 to 13, 17 and 21 were made by a similar procedure.

References: [1]Patent: US4354034,1982,A .

20
[ 50-00-0 ]
[ 13659-23-9 ]
[ 147460-41-1 ]
[ 1009094-06-7 ]

Yield	Reaction Conditions	Operation in experiment
47%		To a solution of MgCl2 (powder 325 mesh, 0.734 g, 7.71 mmol, 2 eq), paraformaldehyde (0.347 g, 11.57 mmol, 3 eq) and Et3N (1.08 mL, 7.71 mmol, 2 eq) in THF (20 mL) was added 276 (0.800 g, 3.68 mmol, 1 eq), heated in the microwave at 160 C for 15 min. TLC (3:2 Hexane:DCM) showed complete consumption of 3. THF was evaporated and the reaction mixture was taken up in EtOAc, washed with brine, dried, filtered and concentrated in vacuo to afford 0.52 g of 277 which was used without purification. Yield 47%

References: [1]Patent: US2008/114167,2008,A1 .Location in patent: Page/Page column 208.

21
[ 13659-23-9 ]
[ 158984-76-0 ]
[ 1150315-94-8 ]

Yield	Reaction Conditions	Operation in experiment
74%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 16.3333h;	A: 4- { [(2-bromo-4-chlorophenyl)oxy]methyl} - 1 -(phenylmethyl)- 1 ,2,3,6- tetrahydropyridineTriphenylphosphine (6.9 g, 26.3 mmol) was dissolved in THF (175 niL) and the solution cooled to 0 0C in an ice bath under nitrogen. Diisopropyl azodicarboxylate (5.3 g, 26.2 mmol) was then added dropwise and the mixture stirred at 0 0C for 20 minutes, during which a white ppt was seen to form. <strong>[13659-23-9]2-Bromo-5-chlorophenol</strong> (4.4 g, 21 mmol) was then added as a solid followed by [1 -(phenylmethyl)- 1,2,3, 6- tetrahydro-4-pyridinyl]methanol (4.3 g, 21 mmol). The mixture was allowed to warm to ambient temperature overnight. The reaction was evaporated to a residue after 16 hours and then purified by FCC on the ISCO (0% to 25% EtOAc/Hex). Fractions containing product were concentrated to give a colorless oil (6.14g, 74%). MS (ES) m/e 393.8 [M+H]+.

References: [1]Patent: WO2009/61881,2009,A1 .Location in patent: Page/Page column 27.

22
[ 13659-23-9 ]
4-(4-chloro-2-(difluoromethoxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide 2,2,2-trifluoroacetate [ No CAS ]

References: [1]Patent: WO2013/122897,2013,A1 .

23
[ 13659-23-9 ]
C₂₆H₂₂ClF₂N₃O₅S₂ [ No CAS ]

References: [1]Patent: WO2013/122897,2013,A1 .

24
[ 16331-46-7 ]
[ 13659-23-9 ]
[ 74-88-4 ]
[ 1006590-10-8 ]