[ CAS No. 66646-88-6 ] {[proInfo.proName]}

Name: 66646-88-6|Methyl 2-(benzylideneamino)acetate|95%
Brand: Ambeed
SKU: A375873
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Quality Control of [ 66646-88-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 66646-88-6 ]

Product Details of [ 66646-88-6 ]

CAS No. :	66646-88-6	MDL No. :	MFCD03701585
Formula :	C₁₀H₁₁NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YOIONBBMZSLNLR-UHFFFAOYSA-N
M.W :	177.20	Pubchem ID :	4169153
Synonyms :

Calculated chemistry of [ 66646-88-6 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	50.8
TPSA :	38.66 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) :	-6.25 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.24
Log Po/w (XLOGP3) :	1.59
Log Po/w (WLOGP) :	1.28
Log Po/w (MLOGP) :	1.32
Log Po/w (SILICOS-IT) :	2.39
Consensus Log Po/w :	1.76

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.02
Solubility :	1.7 mg/ml ; 0.0096 mol/l
Class :	Soluble
Log S (Ali) :	-2.01
Solubility :	1.72 mg/ml ; 0.00971 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.97
Solubility :	0.19 mg/ml ; 0.00107 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.22

Safety of [ 66646-88-6 ]

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 [ 66646-88-6 ]

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

Upstream synthesis route of [ 66646-88-6 ]
Downstream synthetic route of [ 66646-88-6 ]

[ 66646-88-6 ] Synthesis Path-Upstream 1~2

1
[ 66646-88-6 ]
[ 53386-64-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium tetrahydroborate In methanol at -5℃; for 2 h;	To a solution of methyl 2-aminoacetate hydrochloride (15.00 g, 1 16.00 mmol, 1.0 eq) in CH₂C1₂ (150 mL) was added Et₃N (20 mL, 143.3 mmol, 1.2eq) and PhCHO ( 14.6 mL, 143.3 mmol, 1.2eq) in turn. The reaction mixture was stirred at room temperature overnight, and concentrated in vacuo. The residue was diluted with EtOAc and filtered. The filtrate was concentrated in vacuo to afford the crude product methyl 2-(benzylideneamino) acetate, which was used for the next step without further purification.To a solution of methyl 2-(benzylideneamino) acetate in MeOH (200 mL) at -5 °C was added NaBH₄ (2.80 g, 72.8 mmol, 0.55 eq) slowly. The reaction mixture was stirred at -5 °C for 2 h. The reaction mixture was then quenched with water and extracted with EtOAc ( 100 mL x 3). The combined organic phases were washed with water followed bybrine, dried over anhydrous Na₂S0₄ and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20: 1 (v/v) PE/EtOAc) to afford the title compound as colorless oil (21.30 g, 99 percent).
21.3 g	at -5℃; for 2 h;	To a solution of methyl 2-aminoacetate hydrochloride (15.00 g, 116.00 mmol, 1.0 eq) in CH₂Cl₂(150 mL) was added Et₃N (20 mL, 143.3 mmol, 1.2eq) and PhCHO (14.6 mL, 143.3 mmol, 1.2eq) in turn. The reaction mixture was stirred at room temperature overnight, and concentrated in vacuo. The residue was diluted with EtOAc and filtered. The filtrate was concentrated in vacuo to afford the crude product methyl 2-(benzylideneamino)acetate, which was used for the next step without further purification. To a solution of methyl 2-(benzylideneamino) acetate in MeOH (200 mL) at −5° C. was added NaBH₄(2.80 g, 72.8 mmol, 0.55 eq) slowly. The reaction mixture was stirred at −5° C. for 2 h. The reaction mixture was then quenched with water and extracted with EtOAc (100 mL×3). The combined organic phases were washed with water followed by brine, dried over anhydrous Na₂SO₄and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) PE/EtOAc) to afford the title compound as colorless oil (21.30 g, 99percent).

Reference： [1] Patent: WO2013/71697, 2013, A1, . Location in patent: Paragraph 00211
[2] Tetrahedron Letters, 1994, vol. 35, # 49, p. 9293 - 9296
[3] Journal of Organic Chemistry, 1997, vol. 62, # 4, p. 982 - 991
[4] Chemistry - A European Journal, 2005, vol. 11, # 9, p. 2680 - 2688
[5] Patent: US2014/228361, 2014, A1, . Location in patent: Paragraph 0301-0302

2
[ 66646-88-6 ]
[ 119715-66-1 ]

Reference： [1] Tetrahedron Letters, 1988, vol. 29, # 38, p. 4819 - 4822

[ 66646-88-6 ] Synthesis Path-Downstream 1~37

1
[ 4519-46-4 ]
[ 66646-88-6 ]
[ 101235-91-0 ]

Reference： [1]Tetrahedron,1985,vol. 41,p. 2707 - 2716

2
[ 4519-46-4 ]
[ 66646-88-6 ]
[ 101235-81-8 ]
[ 101235-81-8 ]

Reference： [1]Tetrahedron,1985,vol. 41,p. 2707 - 2716

3
[ 66646-88-6 ]
[ 53386-64-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium tetrahydroborate; In methanol; at -5℃; for 2h;	To a solution of methyl 2-aminoacetate hydrochloride (15.00 g, 1 16.00 mmol, 1.0 eq) in CH2C12 (150 mL) was added Et3N (20 mL, 143.3 mmol, 1.2eq) and PhCHO ( 14.6 mL, 143.3 mmol, 1.2eq) in turn. The reaction mixture was stirred at room temperature overnight, and concentrated in vacuo. The residue was diluted with EtOAc and filtered. The filtrate was concentrated in vacuo to afford the crude product methyl 2-(benzylideneamino) acetate, which was used for the next step without further purification.To a solution of methyl 2-(benzylideneamino) acetate in MeOH (200 mL) at -5 C was added NaBH4 (2.80 g, 72.8 mmol, 0.55 eq) slowly. The reaction mixture was stirred at -5 C for 2 h. The reaction mixture was then quenched with water and extracted with EtOAc ( 100 mL x 3). The combined organic phases were washed with water followed bybrine, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20: 1 (v/v) PE/EtOAc) to afford the title compound as colorless oil (21.30 g, 99 %).
21.3 g	With methanol; sodium tetrahydroborate; at -5℃; for 2h;	To a solution of methyl 2-aminoacetate hydrochloride (15.00 g, 116.00 mmol, 1.0 eq) in CH2Cl2 (150 mL) was added Et3N (20 mL, 143.3 mmol, 1.2eq) and PhCHO (14.6 mL, 143.3 mmol, 1.2eq) in turn. The reaction mixture was stirred at room temperature overnight, and concentrated in vacuo. The residue was diluted with EtOAc and filtered. The filtrate was concentrated in vacuo to afford the crude product methyl 2-(benzylideneamino)acetate, which was used for the next step without further purification. To a solution of methyl 2-(benzylideneamino) acetate in MeOH (200 mL) at -5 C. was added NaBH4 (2.80 g, 72.8 mmol, 0.55 eq) slowly. The reaction mixture was stirred at -5 C. for 2 h. The reaction mixture was then quenched with water and extracted with EtOAc (100 mL×3). The combined organic phases were washed with water followed by brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) PE/EtOAc) to afford the title compound as colorless oil (21.30 g, 99%).

Reference： [1]Patent: WO2013/71697,2013,A1 .Location in patent: Paragraph 00211
[2]Tetrahedron Letters,1994,vol. 35,p. 9293 - 9296
[3]Journal of Organic Chemistry,1997,vol. 62,p. 982 - 991
[4]Chemistry - A European Journal,2005,vol. 11,p. 2680 - 2688
[5]Patent: US2014/228361,2014,A1 .Location in patent: Paragraph 0301-0302

4
[ 66646-88-6 ]
[ 174953-30-1 ]
(1R,2S)-2-Methyl-1-[1-phenyl-meth-(E)-ylidene]-amino}-cyclopropanecarboxylic acid methyl ester [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,1996,vol. 7,p. 283 - 284

5
[ 66646-88-6 ]
[ 111836-35-2 ]

Reference： [1]Tetrahedron Letters,1987,vol. 28,p. 1397 - 1400

6
[ 66646-88-6 ]
[ 103057-10-9 ]
2-(Benzylidene-amino)-3-(1-trityl-1H-imidazol-4-yl)-2-(1-trityl-1H-imidazol-4-ylmethyl)-propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hexamethylsilazane; In tetrahydrofuran;	1A. 2-(Benzylidene-amino)-3-(1-trityl-1H-imidazol-4-yl)-2-(1-trityl-1H-imidazol-4-ylmethyl)-propionic acid methyl ester A solution of potassium bis(trimethylsilyl)amide (11.34 g, 54 mmol) in THF (100 ml) was added dropwise to a mixture of (benzylidene-amino)-acetic acid methyl ester (3.83 g, 21.63 mmol) and 4-chloromethyl-1-trityl-1H-imidazole (21.6 g, 60.18 mmol) in THF (200 ml) at -78 C. The resulting solution was warmed to ambient temperature and stirred for 24 hours. After removal of THF, the reaction mixture was subsequently partitioned between ethyl acetate and brine. The aqueous layer was washed two times with ethyl acetate. The ethyl acetate extracts were combined, dried over MgSO4, filtered and concentrated to give the crude title compound of example 1A.
	With potassium hexamethylsilazane; In tetrahydrofuran;	53A. 2-(Benzylidene-amino)-3-(1-trityl-1H-imidazol-4-yl)-2-(1-trityl-1H-imidazol-4-ylmethyl)-propionic acid methyl ester A solution of potassium bis(trimethylsilyl)amide (11.34 g, 54 mmol) in THF (100 ml) was added dropwise to a mixture of (benzylidene-amino)-acetic acid methyl ester (3.83 g, 21.63 mmol) and 4-chloromethyl-1-trityl-1H-imidazole (21.6 g, 60.18 mmol) in THF (200 ml) at -78 C. The resultant solution was warmed to ambient temperature and stirred for 24 hours. After removal of THF, the reaction mixture was subsequently partitioned between ethyl acetate and brine. The aqueous layer was washed two times with ethyl acetate. The ethyl acetate extracts were combined, dried over MgSO4, filtered and concentrated to give the crude title compound of 53A.

Reference： [1]Patent: US6080769,2000,A
[2]Patent: US6194438,2001,B1

7
[ 7283-69-4 ]
[ 66646-88-6 ]
[ 1062148-82-6 ]
3,4-diisobutyl 2-methyl (2R,3R,4R,5S)-5-phenylpyrrolidine-2,3,4-tricarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,4-diaza-bicyclo[2.2.2]octane; (S)-(+)-(3,5-dioxa-4-phosphacyclohepta[2,1-a;3,4-a']dinaphthalen-4-yl)-bis-[(1R)-1-phenethyl]amine; lithium perchlorate In toluene at 0℃; for 17h; optical yield given as %ee; enantioselective reaction;

Reference： [1]Location in patent: experimental part Najera, Carmen; Retamosa, M. De Gracia; Sansano, Jose M. [Angewandte Chemie - International Edition, 2008, vol. 47, # 32, p. 6055 - 6058]

8
[ 585-07-9 ]
[ 66646-88-6 ]
C₁₈H₂₅NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; (22α)-21,22-dihydroxy-2,3-dimethoxy-21,22-dihydrostrychnidin-10-one; 1,8-diazabicyclo[5.4.0]undec-7-ene In chloroform at 0 - 25℃; for 22h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;

Reference： [1]Kim, Hun Young; Shih, Hui-Ju; Knabe, William E.; Oh, Kyungsoo [Angewandte Chemie - International Edition, 2009, vol. 48, # 40, p. 7420 - 7423][Angewandte Chemie, 2009, vol. 121, # 40, p. 7556 - 7559]

9
[ 585-07-9 ]
[ 66646-88-6 ]
C₁₈H₂₅NO₄ [ No CAS ]
C₁₈H₂₅NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl 2-(benzylideneamino)acetate With (22α)-21,22-dihydroxy-2,3-dimethoxy-21,22-dihydrostrychnidin-10-one; silver(I) acetate In toluene at 0℃; for 1h; Inert atmosphere; Stage #2: tert-Butyl methacrylate In toluene at 0 - 25℃; for 22h; Inert atmosphere; Molecular sieve; optical yield given as %ee; enantioselective reaction;

10
[ 128-53-0 ]
[ 66646-88-6 ]
[ 1140972-17-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With silver perchlorate; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); triethylamine; In toluene; at 25℃; for 16h;Darkness;	General procedure: A solution of the imino ester (1 mmol) and dipolarophile (1 mmol) in toluene (5 mL) was added to a suspension containing (R)- or (S)-Binap (0.05 mmol, 31 mg) and AgX (0.05 mmol) in toluene (5 mL). To the resulting suspension triethylamine (0.05 mmol, 7 muL) was added and the mixture was stirred at room temperature and in the absence of the light for 16-48 h (see main text). The precipitate was filtered and the complex was recovered. The organic filtrate was directly evaporated and the residue was purified by recrystallization or by flash chromatography yielding pure endo-cycloadducts.

Reference： [1]Tetrahedron Asymmetry,2010,vol. 21,p. 1184 - 1186
[2]Tetrahedron Asymmetry,2012,vol. 23,p. 1596 - 1606
[3]Synlett,2010,p. 962 - 966
[4]Chemistry - A European Journal,2011,vol. 17,p. 14224 - 14233

11
[ 941-69-5 ]
[ 66646-88-6 ]
[ 118133-86-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With silver(I) acetate In toluene at 20 - 30℃; for 18h;	Pyrrolidines 4a-f; General Procedure General procedure: To a suspension of AgOAc in toluene (3 mL) was added a solution of imino ester (1 mmol) and N-phenylmaleimide (1 mmol) in toluene (2 mL). To the resulting suspension was added Et3N (0.05 mmol, 7 μL) and the mixture stirred at r.t. (20-30 °C) for 18-24 h. The crude reaction mixture was filtered through a small Celite pad. The residue was purified by flash chromatography or the solid products were recrystallized from a mixture of n-hexane/Et2O.
88%	With 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-silver trifluoroacetate; N-ethyl-N,N-diisopropylamine In toluene at 20℃; Darkness;
80%	With cellulose sulfuric acid In ethanol at 20℃; for 28h; diastereoselective reaction;

With 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-silver trifluoroacetate In toluene at 20℃; enantioselective reaction;

Reference： [1]Belveren, Samet; Larrañaga, Olatz; Poyraz, Samet; Dondas, H. Ali; Ülger, Mahmut; Şahin, Ertan; Ferrándiz-Saperas, Marcos; Sansano, José M.; De Gracia Retamosa; De Cózar, Abel [Synthesis, 2019, vol. 51, # 7, p. 1565 - 1577]
[2]Location in patent: experimental part Martin-Rodriguez, Maria; Najera, Carmen; Sansano, Jose M.; De Cozar, Abel; Cossio, Fernando P. [Chemistry - A European Journal, 2011, vol. 17, # 50, p. 14224 - 14233]
[3]Location in patent: experimental part Kumar, Atul; Gupta, Garima; Srivastava, Suman [Journal of Combinatorial Chemistry, 2010, vol. 12, # 4, p. 458 - 462]
[4]Location in patent: experimental part Martin-Rodriguez, Maria; Najera, Carmen; Sansano, Jose M.; Wu, Feng-Liu [Tetrahedron Asymmetry, 2010, vol. 21, # 9-10, p. 1184 - 1186]

12
[ 66646-88-6 ]
[ 624-49-7 ]
[ 479499-50-8 ]
(2R,3R,4R,5S)-trimethyl 5-phenylpyrrolidine-2,3,4-tricarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-((S)-3,3-dimethyl-1-oxo-1-(((S)-1-phenylethyl)amino)butan-2-yl)-2-(diphenylphosphino)benzamide; silver carbonate; In toluene; at 20℃; for 2h;Inert atmosphere;	General procedure: Ligand of 1g (3.132 mg, 0.006 mmol) and Ag2CO3 (0.83 mg, 0.003 mmol,) were dissolved in toluene(1.4 ml). The reaction mixture was stirred for 1h at room temperature, followed by the addition of the activated olefins (0.33 mmol), Et3N (0.015 mmol) and imine substrate (0.3 mmol). Once starting material was consumed (monitored by TLC), the mixture purified by column chromatography to give the corresponding cycloaddition product, which was then directly analyzed by chiral HPLC
	With 2-(diphenylphosphino)-N-((S)-2-(((1S,2S)-2-(isobutylamino)-1,2-diphenylethyl)amino)-2-oxo-1-phenylethyl)benzamide; silver carbonate; In toluene; at 20℃;Inert atmosphere;	General procedure: Precat. 1g (5.51 mg, 0.008 mmol) and Ag2CO3 (1.09 mg, 0.004 mmol), were dissolved in toluene (1.4 ml). The reaction mixture was stirred for 1h at room temperature, followed by the addition of the diethyl maleate 2a (34.4 mg, 0.2 mmol), and imine substrate 3 (0.24 mmol). Once starting material was consumed (monitored by TLC), the mixture was purified by column chromatography to give the corresponding cycloaddition product, which was then directly analyzed by chiral HPLC.

Reference： [1]Tetrahedron Asymmetry,2010,vol. 21,p. 2535 - 2541
[2]Synlett,2017,vol. 28,p. 999 - 1003
[3]Synthesis,2018,vol. 50,p. 2347 - 2358
[4]Heterocycles,2020,vol. 100,p. 585 - 599

13
[ 5117-12-4 ]
[ 66646-88-6 ]
[ 1310430-72-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With (R)-DTBM-segphos; silver trifluoromethanesulfonate; potassium hexamethylsilazane In diethyl ether at 0℃; for 24h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
92%	With (R)-((4,4’-bi-1,3-benzodioxole)-5,5’-diyl)bis(bis(3,5-di-t-butyl-4-methoxyphenyl))phosphine; silver bis(trimethylsilyl)amide In diethyl ether at 0℃; for 24h; Inert atmosphere; optical yield given as %ee; stereoselective reaction;
92%	With (R)-((4,4’-bi-1,3-benzodioxole)-5,5’-diyl)bis(bis(3,5-di-t-butyl-4-methoxyphenyl))phosphine; silver bis(trimethylsilyl)amide In diethyl ether at 0℃; for 24h; enantioselective reaction;

Reference： [1]Yamashita, Yasuhiro; Imaizumi, Takaki; Kobayashi, Sha [Angewandte Chemie - International Edition, 2011, vol. 50, # 21, p. 4893 - 4896]
[2]Yamashita, Yasuhiro; Imaizumi, Takaki; Guo, Xun-Xiang; Kobayashi, Shu [Chemistry - An Asian Journal, 2011, vol. 6, # 9, p. 2550 - 2559]
[3]Yamashita, Yasuhiro; Kobayashi, Shu [Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9420 - 9427]

14
[ 66646-88-6 ]
[ 624-48-6 ]
[ 144538-28-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	With 3-{(S)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl}-2-(phenylthio)indole; silver(I) acetate; triethylamine In diethyl ether at -40℃; for 18h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	4.4. General procedure for the catalytic asymmetric 1,3-dipolar cycloadditon of azomethine ylides General procedure: Under a nitrogen atmosphere, a solution of AgOAc (0.009 mmol) and ligand 2 (0.0099 mmol) in 1.5 mL of Et2O was stirred at room temperature for 1 h. Imino esters (0.3 mmol), Et3N (4.2 μL, 0.03 mmol), and dimethyl maleate (0.36 mmol) were added successively. Once the starting materials were consumed (monitored by TLC), the mixture was passed through a short column of silica gel and the diastereometric ratio (endo/exo) was determined by NMR spectroscopic analysis after removal of the solvent. The residue was purified by column chromatography on silica gel, and then submitted to ee analysis by HPLC with a chiral column.
94%	With N-((S)-3,3-dimethyl-1-oxo-1-(((S)-1-phenylethyl)amino)butan-2-yl)-2-(diphenylphosphino)benzamide; silver carbonate In toluene at 20℃; for 2h; Inert atmosphere; enantioselective reaction;	Representative procedure of 1,3-dipole cycloaddition General procedure: Ligand of 1g (3.132 mg, 0.006 mmol) and Ag2CO3 (0.83 mg, 0.003 mmol,) were dissolved in toluene(1.4 ml). The reaction mixture was stirred for 1h at room temperature, followed by the addition of the activated olefins (0.33 mmol), Et3N (0.015 mmol) and imine substrate (0.3 mmol). Once starting material was consumed (monitored by TLC), the mixture purified by column chromatography to give the corresponding cycloaddition product, which was then directly analyzed by chiral HPLC
94%	With 2-(diphenylphosphino)-N-((S)-2-(((1S,2S)-2-(isobutylamino)-1,2-diphenylethyl)amino)-2-oxo-1-phenylethyl)benzamide; silver carbonate In toluene at 20℃; Inert atmosphere;	C. General procedure A of the Ag2CO3/1g catalyzed cycloaddition of various iminoesters 3 General procedure: Precat. 1g (5.51 mg, 0.008 mmol) and Ag2CO3 (1.09 mg, 0.004 mmol), were dissolved in toluene (1.4 ml). The reaction mixture was stirred for 1h at room temperature, followed by the addition of the diethyl maleate 2a (34.4 mg, 0.2 mmol), and imine substrate 3 (0.24 mmol). Once starting material was consumed (monitored by TLC), the mixture was purified by column chromatography to give the corresponding cycloaddition product, which was then directly analyzed by chiral HPLC.

92%	With (S)-2-(diphenylphosphino)-N-(1-((2-(isobutylamino)benzyl)amino)-3,3-dimethyl-1-oxobutan-2-yl)benzamide; silver(l) oxide In toluene at 20℃; for 4h; stereoselective reaction;
91%	With N-((S)-1-(((1S,2S)-2-(dimethylamino)cyclohexyl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-2-(diphenyl-phosphino)benzamide; silver(l) oxide In toluene at -20℃; Inert atmosphere; enantioselective reaction;	Representative procedure of 1,3-dipole cycloaddition General procedure: Under argon atmosphere, precatalyst 1c or 1e (0.012 mmol) and Ag2O (0.006 mmol) were dissolved in toluene (1.4 mL). The reaction mixture was stirred for 1 h at rt, followed by the addition of maleates 2 or 5 (0.20 mmol) and iminester substrates 3 (0.30 mmol) at -20 oC. Once starting material had been consumed (monitored by TLC), the mixture was purified by column chromatography to give the corresponding cycloaddition product 4 or 6, which was then directly analyzed by chiral HPLC
89%	With tetrakis(acetonitrile)copper(I) perchlorate; C₃₄H₃₃FeN₂PS; triethylamine In toluene at 0℃; for 12h; Inert atmosphere; stereoselective reaction;	4.4 General procedure for catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides General procedure: Under nitrogen atmosphere, a solution of [Cu(CH3CN)4]ClO4 (0.005mmol) and (Rc,SFc)-ImiFerroS 1e (0.0055mmol) in 1 mL of toluene was stirred at room temperature for 1h. The reaction mixture was cooled to 0°C, and then a solution of imino esters 5 (0.5mmol) in 2 mL of toluene, Et3N (0.05mmol) and dimethyl dimelate 6 (0.6mmol) were added successively. Once the material consumed (monitored by TLC), the mixture was filtered through Celite. The filtrate was concentrated in vacuum to give an endo/exo ratio of the crude product (determined by 1H NMR). The residue was purified by flash chromatography (petroleum/EtOAc, 2/1) to afford the cycloadduct, which was then analyzed by chiral HPLC to determine the enantiomeric excess.

Reference： [1]Location in patent: experimental part Han, Mei-Ling; Wang, Dao-Yong; Zeng, Pei-Wei; Zheng, Zhuo; Hu, Xiang-Ping [Tetrahedron Asymmetry, 2012, vol. 23, # 3-4, p. 306 - 312]
[2]Zhou, Zhipeng; Zheng, Xiaojun; Liu, Jialin; Li, Jinlei; Wen, Pushan; Wang, Haifei [Synlett, 2017, vol. 28, # 8, p. 999 - 1003]
[3]Zheng, Xiaojun; Deng, Qifu; Hou, Qinglin; Zhang, Kaiqiang; Wen, Pushan; Hu, Shunqin; Wang, Haifei [Synthesis, 2018, vol. 50, # 12, p. 2347 - 2358]
[4]Jiang, Haiyun; Liu, Jialin; Song, Xinluo; Wang, Haifei; Zhang, Chen [Heterocycles, 2020, vol. 100, # 4, p. 585 - 599]
[5]Gong, Chuliang; Liu, Youshi; Luo, Jie; Wang, Haifei; Zhou, Qingxia; Zhou, Zhipeng [Heterocycles, 2021, vol. 104, # 1, p. 123 - 139]
[6]Han, Fu-Zhong; Yu, Sai-Bo; Zhang, Cheng; Hu, Xiang-Ping [Tetrahedron, 2016, vol. 72, # 21, p. 2616 - 2622]

15
[ 2343-89-7 ]
[ 66646-88-6 ]
[ 1417912-37-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	With tetrakis(acetonitrile)copper(I)tetrafluoroborate; (S)-TF-Biphamphos; triethylamine In dichloromethane at 20℃; Inert atmosphere; enantioselective reaction;

Reference： [1]Yan, Dingce; Li, Qinghua; Wang, Chunjiang [Chinese Journal of Chemistry, 2012, vol. 30, # 11, p. 2714 - 2720]

16
[ 66646-88-6 ]
[ 469898-10-0 ]
C₂₆H₂₁BrN₂O₄ [ No CAS ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 4649 - 4651

17
[ 66646-88-6 ]
[ 469898-10-0 ]
C₂₆H₂₁BrN₂O₄ [ No CAS ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 4649 - 4651

18
[ 22162-14-7 ]
[ 66646-88-6 ]
C₁₀H₁₂N₂O₄*ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile at 20℃; for 6h;	4.C Methyl 2-amino-3-(2-methyl-4-nitro-phenyl)propanoate Hydrochloride (4c) Adapting literature protocols (, methyl 2-amino-3-(2-methyl-4-nitro-phenyl)propanoate Hydrochloride (4c) was prepared through alkylation commercial methyl[(phenylmethylidene)amino]acetate (1.84 g, 10.4 mmol), with 1-(bromomethyl)-4-nitro-benzene (4b) (2.86 g, 12.5 mmol), potassium carbonate (K2CO3) (4.31 g, 31.2 mmol), benzyltriethylammonium chloride (BTEAC) (237 mg, 1.04 mmol) in acetonitrile (MeCN) (30 mL). The reaction mixture was stirred for about 6 hours at room temperature, filtered, and concentrated under reduced pressure using a rotary evaporator. The residue was diluted with diethyl ether (Et2O) and the organic layer was washed with brine. The phases were separated and the organic layer was concentrated to a total volume of about 20 mL. 1.0 M Hydrochloric acid (HCl) (50 mL) was added, and the reaction mixture was kept overnight at room temperature. The reaction mixture was further diluted with diethyl ether (Et2O) and the phases were separated. The aqueous phase was concentrated under reduced pressure using a rotary evaporator.

Reference： [1]Current Patent Assignee: QUADRIGA BIOSCIENCES - US2015/218086, 2015, A1 Location in patent: Paragraph 0602

19
[ 66646-88-6 ]
[ 399-10-0 ]
C₂₅H₂₂FNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With C₃₇H₄₄N₂O₂S; silver fluoride In tetrahydrofuran; ethanol at -20℃; enantioselective reaction;

Reference： [1]Bai, Xing-Feng; Xu, Zheng; Xia, Chun-Gu; Zheng, Zhan-Jiang; Xu, Li-Wen [ACS Catalysis, 2015, vol. 5, # 10, p. 6016 - 6020]

20
[ 66646-88-6 ]
[ 956-02-5 ]
C₂₅H₂₂ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With C₃₇H₄₄N₂O₂S; silver fluoride In tetrahydrofuran; ethanol at -20℃; enantioselective reaction;

Reference： [1]Bai, Xing-Feng; Xu, Zheng; Xia, Chun-Gu; Zheng, Zhan-Jiang; Xu, Li-Wen [ACS Catalysis, 2015, vol. 5, # 10, p. 6016 - 6020]

21
[ 66646-88-6 ]
[ 13380-67-1 ]
(-)-methyl 5-(4-bromophenyl)-4,6-dioxo-3-phenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylate [ No CAS ]
(+)-methyl 5-(4-bromophenyl)-4,6-dioxo-3-phenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2-((1R)-((tert-butylsulfinyl)amino)(phenyl)methyl)-6-(diphenylphosphanyl)-N,N-diisopropylbenzamide; water; silver fluoride; In toluene; at -20℃; for 10h;	General procedure: 4.3. Typical procedure for the synthesis of 6 through thesilver-catalyzed [3+2] cycloaddtion of azomethine ylides4aen with N-aromatic maleimides 5a-h To the AgF (0. 8 mg, 0.0063 mmol, 2.5 mmol%) catalysis inreaction tube, 100 mLH2O was added to dissolve the AgF. Toluene(2 mL) was added and the resulting mixture was stirredfor 5 min. Then sys-(R, Rs)-2a (0.0082 g, 0.0138 mmol, 5.5 mmol%) was added. The mixture was stirred at 20 C for 15 min, theniminoester (0.6 mmol, 1.2 equiv) and maleimide (0.5 mmol,1.0 equiv) were added successively. The reaction was allowedto proceed for 10 h at 20 C, after which 5 mL H2O was addedto quench the reaction. The organic layer was diluted with 10 mLEtOAc and water layer was extracted with EtOAc (5mL2). The combined organic layer was dried with Na2SO4 and con-centrated. A portion of the cured was analysed with 1H NMR todetermine the diastereomeric ratio and recovered. The structuresof some products were known16 and conrmed by NMR, IR andMS. The enantiomeric excesses of the products were determinedby chiral stationary phase HPLC using a chiral column afterpurication.

Reference： [1]Tetrahedron,2016,vol. 72,p. 2690 - 2699

22
[ 395-45-9 ]
[ 66646-88-6 ]
(2R,4R,5S)-methyl 5-phenyl-4-(2-(trifluoromethyl)phenyl)pyrrolidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	With (R)-((4,4’-bi-1,3-benzodioxole)-5,5’-diyl)bis(bis(3,5-di-t-butyl-4-methoxyphenyl))phosphine; tetrakis(actonitrile)copper(I) hexafluorophosphate; potassium <i>tert</i>-butylate at 20℃; for 8h; Inert atmosphere; enantioselective reaction;

Reference： [1]Pascual-Escudero, Ana; de Cózar, Abel; Cossío, Fernando P.; Adrio, Javier; Carretero, Juan C. [Angewandte Chemie - International Edition, 2016, vol. 55, # 49, p. 15334 - 15338][Angew. Chem., 2016, vol. 128, p. 15560 - 15564]

23
[ 772-03-2 ]
[ 66646-88-6 ]
(2R,4S,5S)-methyl 5-phenyl-4-(quinolin-2-yl)pyrrolidine-2-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 15334 - 15338
Angew. Chem.,2016,vol. 128,p. 15560 - 15564,5

24
[ 13816-02-9 ]
[ 66646-88-6 ]
(2R,4S,5S)-methyl 5-phenyl-4-(thiazol-2-yl)pyrrolidine-2-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 15334 - 15338
Angew. Chem.,2016,vol. 128,p. 15560 - 15564,5

25
[ 67-56-1 ]
[ 22162-14-7 ]
[ 66646-88-6 ]
methyl 2-amino-3-(2-methyl-4-nitrophenyl)propanoate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 1-(bromomethyl)-2-methyl-4-nitrobenzene; methyl 2-(benzylideneamino)acetate With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile at 20℃; for 6h; Stage #2: With hydrogenchloride In water at 20℃; Stage #3: methanol With thionyl chloride at 0 - 80℃; for 1h;	4.B Step B: Methyl 2-amino-3-(2-methyl-4-nitro-phenyl)propanoate Hydrochloride (4b) Adapting literature protocols , methyl 2-amino-3-(2-methyl-4-nitro- phenyl)propanoate hydrochloride (4b) was prepared through alkylation commercial methyl [(phenylmethylidene)amino]acetate (1.84 g, 10.4 mmol), with l-(bromom ethyls-nitrobenzene (4a) (2.86 g, 12.5 mmol), potassium carbonate (K2C03) (4.31 g, 31.2 mmol), benzyltriethylammonium chloride (BTEAC) (237 mg, 1.04 mmol) in acetonitrile (MeCN) (30 mL). The reaction mixture was stirred for about 6 hours at room temperature, filtered, and concentrated under reduced pressure using a rotary evaporator. The residue was diluted with diethyl ether (Et20) and the organic layer was washed with brine. The phases were separated and the organic layer was concentrated to a total volume of about 20 mL. 1.0 M Hydrochloric acid (HC1) (50 mL) was added, and the reaction mixture was kept overnight at room temperature. The reaction mixture was further diluted with diethyl ether (Et20) and the phases were separated. The aqueous phase was concentrated under reduced pressure using a rotary evaporator. [0621] Following the General Synthesis of Description 4, the crude material was diluted with anhydrous methanol (MeOH) (20 mL) and treated with excess thionyl chloride (SOCl2) at about 0°C (ice bath). The reaction mixture was subsequently heated to about 80°C (oil bath) for about 1 h before solvents and volatiles were removed under reduced pressure using a rotary evaporator to afford 2.18 g (76% yield) of the target compound (4b) as a colorless solid. LC/MS: Rt = 0.687 min; ESI (pos.) mlz = 239.1 (M+H+)+.

Reference： [1]Current Patent Assignee: QUADRIGA BIOSCIENCES - WO2017/24009, 2017, A1 Location in patent: Paragraph 0620; 0621

26
[ 66646-88-6 ]
[ 624-48-6 ]
[ 603958-86-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-((R)-2-(((S)-2-(dimethylamino)-1-phenylethyl)amino)-2-oxo-1-phenylethyl)-2-(diphenylphosphino)benzamide; silver carbonate In toluene at 20℃; Inert atmosphere; Darkness; enantioselective reaction;	22 4.4 Ag₂CO₃/5f catalyzed the synthesis of endo-8 General procedure: General procedure A of Ag2CO3/5f or 5g catalyzed cycloaddition of various iminoesters 7: Under an N2 atmosphere, a solution of precatalyst 5f or 5g (4.68mg, 0.008mmol) and Ag2CO3 (1.10mg, 0.004mmol) in toluene (1.4ml) in a flame dried glass tube with aluminum foil was stirred for 1h at room temperature, followed by the addition of the dipolarophile (0.2mmol) and the iminoester 7 (0.3mmol). Once the starting material was consumed (monitored by TLC), the mixture was purified by column chromatography to give the corresponding cycloaddition product endo-8, which was then directly analyzed by chiral HPLC.
90%	With C₃₂H₃₂FeNP	13 Example 13 In the formula, M represents a metal catalyst, such as silver or silver acetate, and 5 represents the chiral ferrocene P, N ligand derivative prepared in Example 1. The amount of the metal catalyst and the chiral ferrocene P, N ligand derivative catalyst is about 3% of the reaction raw materials.Experimental results show that when the chiral ferrocene P, N ligand derivative catalyst prepared by the present invention is not added, the enantioselective ee value of the product is 0%. After adding the chiral ferrocene P, N ligand derivative catalyst prepared by the present invention, the product content of the endo configuration is 96%, the reaction yield is 90%, and the enantioselectivity ee value is 92%.

Reference： [1]Hou, Yihui; Zhou, Zhipeng; Liu, Pingle; Wang, Jiankang; Hou, Qinglin; Wen, Pushan; Wang, Haifei [Tetrahedron Asymmetry, 2017, vol. 28, # 7, p. 930 - 938]
[2]Current Patent Assignee: WUHAN TEXTILE UNIVERSITY - CN112300220, 2021, A Location in patent: Paragraph 0081-0091

27
[ 825-44-5 ]
[ 66646-88-6 ]
C₁₈H₁₇NO₄S [ No CAS ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 2580 - 2583

28
[ 1667-11-4 ]
[ 66646-88-6 ]
C₂₃H₂₁NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide In toluene at 60℃; for 3h;	8 Potassium hydroxide (44.9 g, 0.8 mo 1) was added to a toluene solution of the compound (formula ii). 4-Chloromethylbiphenyl (81.lg, 0.4 mol), reaction at 60°C for 3h, add water 300mL, stir 10 min, Liquid separation, add 200mL of 6M dilute hydrochloric acid to several layers. Stir at room temperature for 3h, in liquid separation, the aqueous layer is saturated with Na2CO3 solution to adjust the pH to 7-8. A large amount of white solids precipitated, filtration of biphenylalanine methyl ester (Formula i) 86. lg, Purity (HPLC) 99.9%, the total yield is 84.3%.

Reference： [1]Current Patent Assignee: WEIHAI DISU PHARMACEUTICAL; DISHA PHARMACEUTICAL GROUP - CN104725256, 2018, B Location in patent: Paragraph 0030; 0043; 0046; 0049; 0052; 0055;0058; 0062-0064

29
[ 5042-30-8 ]
[ 66646-88-6 ]
5-phenyl-6-trifluoromethyl-1,2,5,6-tetrahydro-1,2,4-triazine-3-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		Add Gan to a dry 100mL Schlenk reaction flaskMethyl benzaldehyde imine (0.71 g, 4 mmol), AgOAc (67 mg, 0.4 mmol) and Cs2CO3 (1.30 g, 4 mmol) were added to the system 15 mL of tetrahydrofuran and stirred for 3 minutes at room temperature;A solution of CF3CHN2 in tetrahydrofuran (4 mmol, 0.2 M, 20 mL) was added to the system and stirred at room temperature for 24 hours.After the reaction was completed by TLC, the solvent was removed under reduced pressure.Then, 40 mL of ethyl acetate and 20 mL of water were added to the system and the layers were separated. The aqueous phase was extracted with ethyl acetate (10 mL x 3). The organic layers were combined and washed twice with water (20 mL) and dried over anhydrous MgSO4.Column chromatography (eluent: petroleum ether/ethyl acetate = 10/1 to 5/1) to obtain the target productMethyl 5-phenyl-6-trifluoromethyl-1,2,5,6-tetrahydro-1,2,4-triazine-3-carboxylate 0.91 g, yield 80%.

Reference： [1]Patent: CN107935955,2018,A .Location in patent: Paragraph 0016; 0017; 0018

30
[ 21806-61-1 ]
[ 66646-88-6 ]
methyl rel-(3aS,4S,6S,6aR)-6-phenylhexahydro-[1,2]oxathiolo-[3,4-c]pyrrole-4-carboxylate 1,1-dioxide [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2019,vol. 2019,p. 4561 - 4565

31
[ 5453-48-5 ]
[ 66646-88-6 ]
C₁₉H₁₉ClN₂O₃ [ No CAS ]

Reference： [1]Green Chemistry,2019,vol. 21,p. 4609 - 4613

32
[ 6000-43-7 ]
[ 100-52-7 ]
[ 66646-88-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2020,vol. 18,p. 646 - 649

33
[ 3478-78-2 ]
[ 66646-88-6 ]
methyl (2'R,4'S,5'R)-2''-oxo-5'-phenyldispiro[cyclohexane-1,3'-pyrrolidine-4',3''-indoline]-2'-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With tetrakis(acetonitrile)copper(I)tetrafluoroborate; (R)-N-((S)-(4-(tert-butyl)phenyl)((1R,4S)-4,5-dimethyl-3,6-diphenyl-1-phosphabicyclo[2.2.1]hepta-2,5-dien-2-yl)methyl)-2-methylpropane-2-sulfinamide; triethylamine In tetrahydrofuran; ethanol at -20℃; for 4h; Schlenk technique; Inert atmosphere; stereoselective reaction;

Reference： [1]Cui, Hao; Duan, Zheng; Li, Er-Qing; Li, Ke; Mathey, François; Song, Manman; Wang, Congcong; Wang, Yue; Wei, Donghui [Organic and biomolecular chemistry, 2020, vol. 18, # 19, p. 3740 - 3746]

34
[ 15484-46-5 ]
[ 66646-88-6 ]
dimethyl (2S,4S,5S)-4-(hydroxymethyl)-5-phenylpyrrolidine-2,4-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With C₃₆H₃₆FeN₃PS; silver(I) acetate; triethylamine In tetrahydrofuran at 20℃; for 16h; Schlenk technique; Inert atmosphere; enantioselective reaction;

Reference： [1]Fukuzawa, Shin-Ichi; Imae, Kazumi; Inoue, Ayana; Kanemoto, Kazuya; Suzuki, Yuko [Journal of Organic Chemistry, 2021, vol. 86, # 21, p. 14586 - 14596]

35
[ 66646-88-6 ]
[ 84750-93-6 ]
C₁₈H₁₆BrF₂NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With (S)-(+)-5,5’-bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-4,4’-bi-1,3-benzodioxole; tetrakis(actonitrile)copper(I) hexafluorophosphate; potassium <i>tert</i>-butylate at 80℃; for 48h; Inert atmosphere; stereoselective reaction;

Reference： [1]Bao, Longzhu; Ran, Lu; Teng, Huailong; Wang, Chun-Jiang; Xu, Xiao; Yan, Dingce; Yang, Zhenyan [Chemical Science, 2022, vol. 13, # 5, p. 1398 - 1407]

36
[ 1273559-19-5 ]
[ 66646-88-6 ]
methyl (2S,3S,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-nitro-5-phenylpyrrolidine-2-carboxylate [ No CAS ]
C₁₇H₂₃N₃O₆ [ No CAS ]
C₁₇H₂₃N₃O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70 % ee	Stage #1: (Z)-tert-butyl (2-nitrovinyl)carbamate; (benzylidene-amino)-acetic acid methyl ester With anhydrous silver carbonate; (3,5-dioxa-4-phospha-cyclohepta[2,1-<i>a</i>;3,4-<i>a</i>']dinaphthalen-4-yl)-bis-(1-phenyl-ethyl)-amine In toluene Darkness; Stage #2: With triethylamine In toluene at 25℃; for 16h; Darkness; Overall yield = 60 percent; stereoselective reaction;	3.4. General Experimental Procedure for the 1,3 Dipolar Cycloaddition of a-Imino Esters andDipolarophiles General procedure: In a flask covered with aluminum foil, the silver salt (see Schemes 4 and 6), and(Ra,S,S)-15 (see Schemes 4 and 6), and toluene (1 mL) were added, and the resulting mixturewas stirred for 1 h. Then, a solution of -imino ester (1 M, 1 mmol) and dipolarophile(1 M, 1 mmol) in toluene (1 mL) was added. To the resulting suspension, triethylamine(0.025 M, 0.05 mmol or 0.05 M, 0.10 mmol) was added and the mixture was stirred atroom temperature (25 C) for 16-24 h. The crude reaction mixture was filtered througha small celite-path and the residue was purified by flash chromatography, yielding purecycloadducts. The racemic products were formed using 2.5 mol% of (Sa,R,R)-15 and2.5 mol% (Ra,S,S)-15.

Reference： [1]García-Mingüens, Eduardo; Ferrándiz-Saperas, Marcos; de Gracia Retamosa; Nájera, Carmen; Yus, Miguel; Sansano, José M. [Molecules, 2022, vol. 27, # 14]

37
[ 1273559-19-5 ]
[ 66646-88-6 ]
C₁₇H₂₃N₃O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (Z)-tert-butyl (2-nitrovinyl)carbamate; (benzylidene-amino)-acetic acid methyl ester With silver⁽¹⁺⁾ cation; (3,5-Dioxa-4-phospha-cyclohepta[2,1-a;3,4-a']dinaphthalen-4-yl)-bis-((R)-1-phenyl-ethyl)-amine; (3,5-dioxa-4-phospha-cyclohepta[2,1-<i>a</i>;3,4-<i>a</i>']dinaphthalen-4-yl)-bis-(1-phenyl-ethyl)-amine In toluene Darkness; Stage #2: With triethylamine In toluene at 25℃; Darkness;	3.4. General Experimental Procedure for the 1,3 Dipolar Cycloaddition of a-Imino Esters andDipolarophiles General procedure: In a flask covered with aluminum foil, the silver salt (see Schemes 4 and 6), and(Ra,S,S)-15 (see Schemes 4 and 6), and toluene (1 mL) were added, and the resulting mixturewas stirred for 1 h. Then, a solution of -imino ester (1 M, 1 mmol) and dipolarophile(1 M, 1 mmol) in toluene (1 mL) was added. To the resulting suspension, triethylamine(0.025 M, 0.05 mmol or 0.05 M, 0.10 mmol) was added and the mixture was stirred atroom temperature (25 C) for 16-24 h. The crude reaction mixture was filtered througha small celite-path and the residue was purified by flash chromatography, yielding purecycloadducts. The racemic products were formed using 2.5 mol% of (Sa,R,R)-15 and2.5 mol% (Ra,S,S)-15.

Reference： [1]García-Mingüens, Eduardo; Ferrándiz-Saperas, Marcos; de Gracia Retamosa; Nájera, Carmen; Yus, Miguel; Sansano, José M. [Molecules, 2022, vol. 27, # 14]

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P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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

[ CAS No. 66646-88-6 ] {[proInfo.proName]}

Quality Control of [ 66646-88-6 ]

Related Doc. of [ 66646-88-6 ]

Product Details of [ 66646-88-6 ]

Calculated chemistry of [ 66646-88-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 66646-88-6 ]

Application In Synthesis of [ 66646-88-6 ]

[ 66646-88-6 ] Synthesis Path-Upstream 1~2

[ 66646-88-6 ] Synthesis Path-Downstream 1~37

Related Functional Groups of [ 66646-88-6 ]

Amino Acid Derivatives

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 66646-88-6 ]