[ CAS No. 76189-56-5 ] {[proInfo.proName]}

Name: 76189-56-5|(S)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthalene|97%
Brand: Ambeed
SKU: A376699
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2D 3D

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Quality Control of [ 76189-56-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 76189-56-5 ]

SDS Specification

Alternatived Products of [ 76189-56-5 ]

Product Details of [ 76189-56-5 ]

CAS No. :	76189-56-5	MDL No. :	MFCD00010805
Formula :	C₄₄H₃₂P₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	622.67	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 76189-56-5 ]

Physicochemical Properties

Num. heavy atoms :	46
Num. arom. heavy atoms :	44
Fraction Csp3 :	0.0
Num. rotatable bonds :	7
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	204.3
TPSA :	27.18 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-1.99 cm/s

Lipophilicity

Log Po/w (iLOGP) :	5.36
Log Po/w (XLOGP3) :	11.42
Log Po/w (WLOGP) :	9.18
Log Po/w (MLOGP) :	9.23
Log Po/w (SILICOS-IT) :	12.45
Consensus Log Po/w :	9.53

Druglikeness

Lipinski :	2.0
Ghose :	None
Veber :	0.0
Egan :	1.0
Muegge :	3.0
Bioavailability Score :	0.17

Water Solubility

Log S (ESOL) :	-11.14
Solubility :	0.0000000045 mg/ml ; 0.0 mol/l
Class :	Insoluble
Log S (Ali) :	-11.97
Solubility :	0.0000000007 mg/ml ; 0.0 mol/l
Class :	Insoluble
Log S (SILICOS-IT) :	-18.22
Solubility :	3.75e-16 mg/ml ; 6.03e-19 mol/l
Class :	Insoluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	5.94

Safety of [ 76189-56-5 ]

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 [ 76189-56-5 ]

* 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 [ 76189-56-5 ]

[ 76189-56-5 ] Synthesis Path-Downstream 1~26

1
[ 94041-18-6 ]
[ 76189-56-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With trichlorosilane; triethyl phosphite In tetrahydrofuran; toluene at 100℃; for 3h;
94%	With 1,3-diphenyldisiloxane In toluene at 110℃; Sealed tube; chemoselective reaction;
91%	Stage #1: [1,1'-binaphthalene]-2,2'-diylbis(diphenylphosphine oxide) With 1,1,3,3-Tetramethyldisiloxane In toluene at 85℃; for 20h; Stage #2: With sodium hydroxide; water In toluene for 0.25h;	1.2 2. Reduction of BINAPO; The BINAP oxide (300 mg, 0.46 mmol, 1 eq.) is placed in a reaction tube equipped with a stirrer and under an inert atmosphere.2 ml of toluene and (0.5 ml, 2.8 mmol, 6 eq.) of tetra-methyldisiloxane and (0.065 ml, 0.23 mmol, 0.5 eq.) of titanium isopropoxide are then added.The reaction mixture is then heated at 85° C. and stirred for 20 hours.It is cooled and 1 ml of sodium hydroxide (3N) is added.The mixture is allowed to stir for 15 minutes and then 5 ml of dichloromethane are added.The mixture is filtered.The organic phase is recovered and then dried and evaporated so as to obtain 280 mg of a white solid.The solid is taken up in 3 ml of pentane and filtered over a sintered glass funnel.A white solid of BINAP is obtained.260 mg of product are recovered, which corresponds to a yield of 91%.The product obtained, BINAP, has the following NMR characteristics:m=260 mg.1H NMR (300 MHz, CDCl3): 6.80 (d, 4H, J=3.7), 7.2-7.3 (m, 8H), 7.3-7.5 (m, 12H), 7.6-7.7 (m, 4H), 7.8-7.9 (m, 4H).31P NMR (81 MHz, CDCl3): -14.63.

23%	Stage #1: [1,1'-binaphthalene]-2,2'-diylbis(diphenylphosphine oxide) With trityl tetrakis(pentafluorophenyl)borate In ⁽²⁾H₈-toluene at 20℃; Glovebox; Inert atmosphere; Stage #2: With phenylsilane In ⁽²⁾H₈-toluene at 100℃; for 24h; Glovebox; Inert atmosphere; Sealed tube;
96 %Chromat.	With AlH₃*TEA In hexane at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique;	Compound IIIa (general procedure). General procedure: Triphenylphosphine oxide or sulfide (1 mmol), dry hexane (1 mL), and Ic (1 mmol) were added to a Schlenk tube under the atmosphere of nitrogen. The reaction was carried out at room temperature for 10 min and monitored by TLC. Upon completion of the process the reaction mixture was filtered by silica gel and washed several times with ethyl acetate. Ethyl acetate was evaporated and the residue purified by flash chromatography on silica gel with pure cyclohexane toafford the desired phosphine. The yield was determined by GC without additional purification.
	Multi-step reaction with 2 steps 1: 1,4-dioxane / 0.5 h / 20 °C / Schlenk technique; Inert atmosphere 2: sodium hydrogencarbonate; sodium hydride; 15-crown-5 / 1,4-dioxane / 24 h / 150 °C / Schlenk technique; Inert atmosphere

Reference： [1]Wu, Hai-Chen; Yu, Jin-Quan; Spencer, Jonathan B. [Organic Letters, 2004, vol. 6, # 25, p. 4675 - 4678]
[2]Buonomo, Joseph A.; Eiden, Carter G.; Aldrich, Courtney C. [Chemistry - A European Journal, 2017, vol. 23, # 58, p. 14434 - 14438]
[3]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; SOLVAY - US2008/214857, 2008, A1 Location in patent: Page/Page column 12
[4]Landais, Yannick; Laye, Claire; Lusseau, Jonathan; Robert, Frédéric [Advanced Synthesis and Catalysis, 2021, vol. 363, # 12, p. 3035 - 3043]
[5]Yang, Shuyan; Han, Xinxin; Luo, Minmin; Gao, Jing; Chu, Wenxiang; Ding, Yuqiang [Russian Journal of General Chemistry, 2015, vol. 85, # 5, p. 1156 - 1160][Zh. Obshch. Khim.]
[6]Jin, Hongyu; Gu, Chengshan; Xiao, Zhihuan; Tan, Qihang; Liu, Long; Han, Li-Biao; Chen, Wen-Hao; Chen, Tieqiao [European Journal of Organic Chemistry, 2023, vol. 26, # 29]

2
[ 76189-56-5 ]
[ 94041-18-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dihydrogen peroxide In dichloromethane; water at 0 - 20℃; for 4h;	1 (S)- or (R)-BINAP (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) (3 g, 4.81 mmol, 1 eq.) dissolved in 100 mL of CH2Cl2 is placed in a 250 mL round-bottomed flask. The mixture is cooled to 0° C. and 10 mL of 35% by weight aqueous hydrogen peroxide solution are added. The mixture is stirred while being allowed to return to room temperature, for four hours. 100 mL of water are then added. The organic phase is separated out and the aqueous phase is extracted with CH2Cl2. The combined organic phases are washed with saturated sodium bisulfite. The solution is checked for the absence of peroxide, and is then dried over sodium sulfate and evaporated. A white solid is obtained (m=3.14 g, 4.8 mmol, i.e. quantitative yield). The characterization of the diphosphine in dioxide form (BINAPO) is as follows: 1H NMR (300 MHz, CDCl3): 6.80 (d, 4H, J=3.7), 7.2-7.3 (m, 8H), 7.3-7.5 (m, 12H), 7.6-7.7 (m, 4H), 7.8-7.9 (m, 4H) 31P NMR (81 MHz, CDCl3): 28.67 melting point: 256-258° C.
100%	With dihydrogen peroxide In dichloromethane for 2h; Cooling with ice;
100%	With dihydrogen peroxide In dichloromethane; water at 20℃; for 3h; Glovebox; Inert atmosphere;

98%	With dihydrogen peroxide In dichloromethane; water for 0.0833333h;
97%	With dihydrogen peroxide In dichloromethane at 20℃; for 5h;
96%	With dihydrogen peroxide In dichloromethane at 5 - 20℃;	1 (1,l’-Binaphthalen-2,2’-diyl)bis(diphenylphosphine) (124.00 g, 199.14 mmol, 1 eq) was suspended in dichloromethane (1.75 L) and cooled to 5°C with an ice bath. Hydrogen peroxide (61.0 mL, 597.4 mmol, 3 eq) was added slowly to the suspension within 1 h. The ice bath was removed and the suspension was stirred overnight at room temperature. The mixture was washed in portions with brine (2 x 150 mL per 600 mL reaction solution). The organic phase was collected, dried over sodium sulphate, filtered and the solvent was evaporated. The crude product was suspended in a mixture of n-hexane and DCM (400 mL, 95:5, vol:vol), filtered, washed with n-hexane and dried under vacuum overnight.Yield: 125,07g (96 %), white powder.Purity: HPLC: 99.5 %Melting point: 302 °C (from DSC (peak at 10 K]min))
95%	With Selectfluor In water; acetonitrile at 22℃; for 3h;	13 Procedure I2I: Phosphine oxidation To a vial was added 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene (1.000 g, 1.606 mmol), acetonitrile (16 ml) and water (0.319 ml, 17.71 mmol) and Selectfluor (1.138 g, 3.21 mmol). This suspension was stirred at 22°C for 3 h. LCMS showed the reaction was complete. The reaction was concentrated, re-suspended in water, sonicated to make a fine powder and filtered. The collected solid was dried in a 50°C vacuum oven overnight to give a fine white powder. Yield -95%.
95%	With water; Selectfluor In acetonitrile at 22℃; for 3h;	13.I2 Procedure I2I: Phosphine oxidation To a vial was added 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene (1.000 g, 1.606 mmol), acetonitrile (16 ml) and water (0.319 ml, 17.71 mmol) and Selectfluor (1.138 g, 3.21 mmol). This suspension was stirred at 22°C for 3 h. LCMS showed the reaction was complete. The reaction was concentrated, re-suspended in water, sonicated to make a fine powder and filtered. The collected solid was dried in a 50°C vacuum oven overnight to give a fine white powder. Yield -95%.
75%	With dihydrogen peroxide In water; acetone for 16h;
	With air; triethyl borane In tetrahydrofuran; hexane at 20℃; for 1h;
	With dihydrogen peroxide In dichloromethane; acetone at 0℃;
	With dihydrogen peroxide
	With dihydrogen peroxide In dichloromethane at 30℃; for 16h;
	With dihydrogen peroxide In tetrahydrofuran; water at 20℃; Schlenk technique; Inert atmosphere;

Reference： [1]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; SOLVAY - US2007/10695, 2007, A1 Location in patent: Page/Page column 20
[2]Seki, Tomohiro; McEleney, Kevin; Crudden, Cathleen M. [Chemical Communications, 2012, vol. 48, # 51, p. 6369 - 6371]
[3]Landais, Yannick; Laye, Claire; Lusseau, Jonathan; Robert, Frédéric [Advanced Synthesis and Catalysis, 2021, vol. 363, # 12, p. 3035 - 3043]
[4]Petersson, Maria J.; Loughlin, Wendy A.; Jenkins, Ian D. [Chemical Communications, 2008, # 37, p. 4493 - 4494]
[5]Location in patent: experimental part Hatano, Bunpei; Hashimoto, Kazuyuki; Katagiri, Hiroshi; Kijima, Tatsuro; Murakami, Satoshi; Matsuba, Shigeru; Kusakari, Miho [Journal of Organic Chemistry, 2012, vol. 77, # 7, p. 3595 - 3597]
[6]Current Patent Assignee: SAMSUNG SDI CO.,LTD. - WO2016/207224, 2016, A1 Location in patent: Page/Page column 20; 21
[7]Current Patent Assignee: SERVIER MONDE - WO2022/36033, 2022, A2 Location in patent: Paragraph 00431; 00475-00476
[8]Current Patent Assignee: SERVIER MONDE - WO2022/36033, 2022, A2 Location in patent: Paragraph 00431; 00475-00476
[9]Busacca, Carl A.; Raju, Ravinder; Grinberg, Nelu; Haddad, Nizar; James-Jones, Paul; Lee, Heewon; Lorenz, Jon C.; Saha, Anjan; Senanayake, Chris H. [Journal of Organic Chemistry, 2008, vol. 73, # 4, p. 1524 - 1531]
[10]Location in patent: experimental part Motoshima, Kosuke; Sato, Akinori; Yorimitsu, Hideki; Oshima, Koichiro [Bulletin of the Chemical Society of Japan, 2007, vol. 80, # 11, p. 2229 - 2231]
[11]Location in patent: experimental part Lam, Kim-Hung; Chui, Chung-Hin; Gambari, Roberto; Wong, Raymond Siu-Ming; Cheng, Gregory Yin-Ming; Lau, Fung-Yi; Lai, Paul Bo-San; Tong, See-Wai; Chan, Kit-Wah; Wong, Wai-Yeung; Chan, Albert Sun-Chi; Tang, Johnny Cheuk-On [European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 5527 - 5530]
[12]Rajendran, Kamalraj V.; Gilheany, Declan G. [Chemical Communications, 2012, vol. 48, # 6, p. 817 - 819]
[13]Buonomo, Joseph A.; Eiden, Carter G.; Aldrich, Courtney C. [Chemistry - A European Journal, 2017, vol. 23, # 58, p. 14434 - 14438]
[14]Jin, Hongyu; Gu, Chengshan; Xiao, Zhihuan; Tan, Qihang; Liu, Long; Han, Li-Biao; Chen, Wen-Hao; Chen, Tieqiao [European Journal of Organic Chemistry, 2023, vol. 26, # 29]

3
[ 625394-57-2 ]
[ 76189-56-5 ]
[ 625394-33-4 ]

Yield	Reaction Conditions	Operation in experiment
79.6%	With piperazine; sodium t-butanolate In toluene at 95℃; for 18h;	3.A Synthesis of 4-(4-chloro-benzenesulfonyl)-6-methyl-8-piperazin-1-yl-3,4-dihydro-2H-benzo[1,4]oxazine ;A three neck flask was charged with tris(dibenzylideneacetone)dipalladium(0) (9.1 mg, 0.001 mmol, 2 mol % Pd), (+-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (15.5 mg, 0.025 mmol, 5 mol %), and sodium-tert-butoxide (67 mg, 0.7 mmol) and flushed with nitrogen.A solution of 8-bromo-4-(4-chloro-benzenesulfonyl)-6-methyl-3,4-dihydro-2H-benzo[1,4]oxazine (201 mg, 0.5 mmol) and piperazine (129 mg, 1.5 mmol) in toluene (5 ML) was added.The mixture was heated to 95° C. and stirred for 18 hours.The mixture was cooled to room temperature, taken up in ethyl acetate and filtered.The organic phase was washed with water (220 ML) and extracted into 10% aqueous HCl (220 ML).The combined aqueous extracts were basified with solid potassium carbonate and extracted into ethyl acetate (2*20 ML).The combined organic extract was dried (K2CO3), filtered and concentrated to give the title compound as an oil (163 mg, 79.6%).The hydrochloride salt was prepared from ethanol-hydrogen chloride. MS: MH+=408. M.p. 147.9-152.9° C.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2003/232825, 2003, A1 Location in patent: Page 30

4
[ 625394-59-4 ]
[ 76189-56-5 ]
[ 57260-71-6 ]
[ 625394-63-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium t-butanolate In toluene at 95℃; for 12h;	3.B.1 Synthesis of 4-benzenesulfonyl-6-chloro-8-piperazin-1-yl-3,4-dihydro-2H-benzo[1,4]oxazine A three neck flask was charged with tris(dibenzylideneacetone)dipalladium(0) (6.4 mg, 0.007 mmol, 2 mol % Pd), racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (10.8 mg, 0.017 mmol, 5 mol %), and sodium tert-butoxide (47 mg, 0.48 mmol) and flushed with nitrogen.A solution of 4-benzenesulfonyl-8-bromo-6-chloro-3,4-dihydro-2H-benzo[1,4]oxazine (165 mg, 0.35 mmol) and piperazine-1-carboxylic acid tert-butyl ester (71.1 mg, 0.38 mmol) in toluene (2 ML) was added.The mixture was heated to 95° C. and stirred for 12 hours.The mixture was cooled to room temperature, taken up in ethyl acetate, filtered and concentrated. The crude material was purified by flash chromatography on silica gel (eluting with hexane-ethyl acetate; 7:3, v/v) to give 4-(4-Benzenesulfonyl-6-chloro-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-piperazine-1-carboxylic acid tert-butyl ester as an oil (129 mg, 75%). MS: MH+=494.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2003/232825, 2003, A1 Location in patent: Page 31

5
[ 625394-74-3 ]
[ 76189-56-5 ]
[ 625394-65-2 ]

Yield	Reaction Conditions	Operation in experiment
48%	With sodium t-butanolate In toluene at 95℃; for 12h;	4.2 Synthesis of 8-bromo-2,3-dihydro-benzo[1,4]oxazine A three neck flask was charge with tris(dibenzylideneacetone)dipalladium(0) (0.37 g, 0.0004 mol, 2 mol % Pd), (+) racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.64 g, 0.001 mol, 5 mol % Pd), and sodium tert-butoxide (2.7 g, 0.028 mol) and flushed with nitrogen.A solution of 2-(2,6-dibromo-phenoxy)ethylamine (6 g, 0.02 mol) in toluene (50 ML) was added.The mixture was heated to 95° C. and was stirred for 12 h.The mixture was cooled to room temperature, taken up in ethyl acetate, filtered and concentrated.The crude material was purified by flash chromatography on silica gel (eluding with hexane-ethyl acetate; 7:3, v/v) to give 8-bromo-3,4-dihydro-2H-benzo[1,4]oxazine as an oil (275 mg, 48%).The hydrochloride salt was prepared from ethanol-hydrogen chloride. MS: MH+=214. M.p. 184.1-195.4° C.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2003/232825, 2003, A1 Location in patent: Page 31

6
[ 123-75-1 ]
[ 619-42-1 ]
argon [ No CAS ]
2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl [ No CAS ]
[ 129414-26-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With caesium carbonate In toluene	a a. a. 4-Pyrrolidin-1-yl-benzoic Acid Methyl Ester An oven-dried reaction tube was charged with cesium carbonate (2.12 g, 6.51 mmol) that had been finely ground with a pestle and mortar under an atmosphere of argon. Tris(dibenzylideneacetone)dipalladium(0) (42.5 mg, 1.5 mol %) and (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (43.4 mg, 1.5 mol %) were added and the tube charged with argon. Pyrrolidine (0.39 g, 5.58 mmol), methyl-4-bromobenzoate (1.00 g, 4.65 mmol) and toluene (10 ml) were added and the mixture heated to 100° C. with vigorous stirring until the starting material had been consumed as judged by hpic. The mixture was cooled to room temperature, diluted with ether (20 ml), filtered and concentrated. Purification by column chromatography gave the title compound (0.80 g, 84%) as a solid. MS (M+H+): 206.

Reference： [1]Current Patent Assignee: MEDIVIR AB - US2003/186962, 2003, A1

7
[ 288398-37-8 ]
[ 76189-56-5 ]
[ 95-53-4 ]
[ 288398-42-5 ]

Yield	Reaction Conditions	Operation in experiment
61%	With caesium carbonate In ethyl acetate; toluene	245.a EXAMPLE 245 a) Methyl 4-[(2-methylphenyl)amino]-5-methylthiothiophene-2-carboxylate A dry mixture of 100 mg (0.374 mmol) of methyl 4-bromo-5-methylthiothiophene-2-carboxylate, 51 mg (14.9 mole %) of tris(dibenzylideneacetone)dipalladium (Lancaster, Pelham, N.H.), 52 mg (22.3 mole %) of racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (Strem, Newburyport, Mass.), 183 mg of (0.56 mmol, 1.5 eq) cesium carbonate (Aldrich Chemical Co., Milwaukee, Wis.), and 71 μL (0.49 mmol, 1.3 eq) of 2-methylaniline (Aldrich Chemical Co., Milwaukee, Wis.) was added to an oven-dried 1-dram glass vial. This vial was flushed with dry argon in a glove bag, dry toluene (750 μL, 0.5 M) was added, and the assembly was heated at 100° C. for 40 h. To the cooled suspension ethyl acetate (4 mL) was added, the mixture passed through 1 inch of Celite, washed with ethyl acetate (2*4 mL) and the solvents removed in vacuo. Purification by preparative thin-layer chromatography (1:1 dichloromethane/hexanes) gave 67 mg of the title compound (61%) as a yellow oil. 1H-NMR (CDCl3, 400 MHz) δ7.64 (s, 1 H), 7.23-6.94 (m, 4 H), 5.91 (br s, 1 H), 3.88 (s, 3 H), 2.41 (s, 3 H), 2.31 (s, 3 H). Mass spectrum (ESI, m/z): Calcd. for C14H15NO2S2, 294.1 (M+H), found 294.2.
61%	With caesium carbonate In ethyl acetate; toluene	245.a EXAMPLE 245 a) Methyl 4-[(2-methylphenyl)amino]-5-methylthiothiophene-2-carboxylate A dry mixture of 100 mg (0.374 mmol) of methyl 4-bromo-5-methylthiothiophene-2-carboxylate, 51 mg (14.9 mole %) of tris(dibenzylideneacetone)dipalladium (Lancaster, Pelham, N.H.), 52 mg (22.3 mole %) of racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (Strem, Newburyport, Mass.), 183 mg of (0.56 mmol, 1.5 eq) cesium carbonate (Aldrich Chemical Co., Milwaukee, Wis.), and 71 μL (0.49 mmol, 1.3 eq) of 2-methylaniline (Aldrich Chemical Co., Milwaukee, Wis.) was added to an oven-dried 1-dram glass vial. This vial was flushed with dry argon in a glove bag, dry toluene (750 μL, 0.5 M) was added, and the assembly was heated at 100° C. for 40 h. To the cooled suspension ethyl acetate (4 mL) was added, the mixture passed through 1 inch of Celite, washed with ethyl acetate (2*4 mL) and the solvents removed in vacuo. Purification by preparative thin-layer chromatography (1:1 dichloromethane/hexanes) gave 67 mg of the title compound (61%) as a yellow oil. 1H-NMR (CDCl3, 400 MHz) δ 7.64 (s, 1H), 7.23-6.94 (m, 4H), 5.91 (br s, 1H), 3.88 (s, 3H), 2.41 (s, 3H), 2.31 (s, 3H). Mass spectrum (ESI, m/z): Calcd. for C14H15NO2S2, 294.1 (M+H), found 294.2.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2002/37915, 2002, A1
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - US6291514, 2001, B1

8
[ 626-55-1 ]
[ 370880-16-3 ]
[ 76189-56-5 ]
[ 370880-50-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium t-butanolate In toluene	30.A tert-butyl (3aS,6aS)-5-(3-pyridinyl)hexahydropyrrolo [3,4-b]pyrrole-1 (2H)-carboxylate EXAMPLE 30A tert-butyl (3aS,6aS)-5-(3-pyridinyl)hexahydropyrrolo [3,4-b]pyrrole-1 (2H)-carboxylate The product from Example 15E (0.71 g, 3.30 mmol) in toluene (33 mL) was treated with tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, available from Alfa Aesar) (61 mg, 0.10 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP, available from Strem Chemicals) (83 mg, 0.10 mmol), 3-bromopyridine (available from Aldrich Chemical Co.,) (0.58 g, 3.70 mmol), and sodium tert-butoxide (available from Aldrich Chemical Co.,) (0.54 g, 5.60 mmol). After heating at 80° C. for 16 hours, the mixture was poured into diethyl ether (100 mL), washed with brine (100 mL), dried(MgSO4) and concentrated under reduced pressure. The residue was purified by chromatography (SiO2, 5% MeOH/CH2Cl2) to provide the title compound as a yellow oil (0.87 g, 91% yield). MS (DCI/NH3) m/z 290 (M+H)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/19388, 2002, A1

9
[ 1013-88-3 ]
[ 405306-72-1 ]
[ 76189-56-5 ]
[ 405306-74-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium t-butanolate In water; ethyl acetate; toluene	48 Preparation of benzhydrylidene-(3-benzyl-1,2,3,4,5,6-hexahydro-azepino[4,5-b]indol-10-yl)amine Example 48 Preparation of benzhydrylidene-(3-benzyl-1,2,3,4,5,6-hexahydro-azepino[4,5-b]indol-10-yl)amine A mixture of 3-benzyl-10-bromo-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.71 g, 2.00 mmol), benzophenone imine (0.44 g, 0.40 mL, 2.40 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.037 g, 0.040 mmol), (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.075 g, 0.120 mmol), and sodium tert-butoxide (0.269 g, 2.80 mmol) in toluene (20.0 mL) was refluxed for 16 h. After cooling to room temperature, water and ethyl acetate were added, and the pahases separated. The aqueous layer was extracted with ethyl acetate (2*). The combined ethyl acetate solution was dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to dryness and the residue was subjected to column chromatography (silica gel, 30% EtOAc/hexane, 1% Et3N) to afford a yellow fluffy solid as the title compound (0.855 g, 94%): mp>71° C. (dec.); 1H NMR (300 MHz, CDCl3) δ 7.82-7.80, 7.65, 7.66-7.11, 6.82-6.79, 6.73, 5.95, 3.78, 3.20-3.16, 2.90-2.78; MS (ESI+) m/z 456 (M++H).

Reference： [1]Current Patent Assignee: ACKER; PFIZER INC; FRANK (inventors); FU; FISHER (inventors); ENNIS, INC. - US2002/77318, 2002, A1

10
[ 183244-55-5 ]
[ 98327-87-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydroxide; trichlorosilane; 2,3-Dimethylaniline In toluene	12 Synthesis of (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl Example 12 Synthesis of (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl Trichlorosilane (0.95 ml, 9.4 mmol) was added to a mixture of (R)-2-diphenylphosphino-2'-diphenylphosphinyl-1,1'-binaphthyl (1.5 g, 2.35 mmol), dimethylaniline (4.8 ml, 4.4 mmol) and toluene (11 ml). The resulting reaction mixture was stirred for 1 hour at 90° C. and thereafter heated at reflux for 16 hours. The reaction mixture was cooled in an ice/water bath, and 3N NaOH solution (20 ml) was added to the reaction mixture. The aqueous layer was extracted with toluene and the organic layer was washed with water (10 ml), 1N hydrochloric acid (20 ml) and water (10 ml) in that order, followed by concentrating the organic solution. Then, the organic solution was purified by silica gel column chromatography (hexane:ethyl acetate=1:0 to 1:1 by volume) to obtain 1.34 g (yield: 92%) of the above captioned compound as a white solid. mp: 241 to 242° C. [α]D24: -228° (c 0.679, benzene) 31 P-NMR(CDCl3)δ: -12.8(s) CI-Mass spectrum m/z: 622(M+)
92%	With hydrogenchloride; sodium hydroxide; trichlorosilane; 2,3-Dimethylaniline In water; toluene	2.2 (2) (2) Synthesis of (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl 0.95 ml (9.4 mmol) of trichlorosilane was added to a mixture comprising 1.5 g (2.35 mmol) of (R)-2-diphenylphosphinyl-2'-diphenylphosphino-1,1'-binaphthyl, 4.8 ml (4.4 mmol) of dimethylaniline and 30 ml of toluene. The resultant mixture was then stirred at 90° C. for 1 hour and for 16 hours while refluxing. The reaction mixture thus obtained was cooled in an ice water bath, and 20 ml of a 3 N NaOH solution was added thereto. The resultant aqueous layer was extracted with toluene. The thus obtained organic layer was then washed with 10 ml of water, with 20 ml of a 1 N hydrochloric acid solution, and with 10 ml of water. After concentration, the resultant solution was purified by silica gel chromatography (hexane:ethyl acetate=1:0 to 1:1) to obtain 1.34 g (yield 92%) of the objective compound as a white solid. The physico-chemical properties of the product were measured as follows. mp 241° to 242° C. [α]D24 -228° (c 0.68, benzene) 31 P NMR (CDCl3) δ-12.8(s) CI-Mass spectrum m/z 622 (M+)
43 %	With phenylsilane; 1-bromo-4-methyl-1-phenyl-2,3-dihydro-1H-phosphol-1-ium bromide; Diethyl 2-bromomalonate In 1,2-dichloro-ethane at 20℃; Inert atmosphere; Schlenk technique;

Reference： [1]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US5922918, 1999, A
[2]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US5693868, 1997, A
[3]Xue, Jing; Zhang, Yu-Shan; Huan, Zhen; Yang, Jin-Dong; Cheng, Jin-Pei [Journal of the American Chemical Society, 2023]

11
[ 285549-29-3 ]
[ 104-94-9 ]
[ 76189-56-5 ]
[ 285548-83-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium t-butanolate In hexane; ethyl acetate; toluene	7-Isopropyl-5-[(4-methoxy-phenyl)-amino]-3,3,6-trimethyl-2,3-dihydro-benzofuran (Compound 52) General Procedure K: 7-Isopropyl-5-[(4-methoxy-phenyl)-amino]-3,3,6-trimethyl-2,3-dihydro-benzofuran (Compound 52) General Procedure K: A mixture of 5-bromo-7-isopropyl-3,3,6-trimethyl-2,3-dihydro-benzofuran (Compound 50, 0.56 g, 1.98 mmol), p-anisidine (0.48 g, 3.96 mmol), sodium tert-butoxide (0.27 g, 2.77 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.020 g, 0.02 1 mmol) and (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.040 g, 0.064 mmol) in 6 mL of anhydrous toluene was heated at 80° C. under argon overnight. The reaction mixture was cooled to ambient temperature, diluted with diethylether and filtered. The filtrate was evaporated in vacuo to a residue which on flash column chromatography using 10% ethyl acetate in hexane as the eluent afforded the title compound (0.6 g, 93%) as a pink solid. 1 H NMR (300 MHz, CDCl3): δ 6.76 (d, 2H, J=8.9 Hz), 6.75 (s, 1H), 6.61 (d, 2H, J=8.9 Hz), 5.0 (s, 1H), 4.15 (s, 2H), 3.71 (s, 3H), 3.24 (heptet, 1H, J=7.0 Hz), 2.17 (s, 3H), 1.33 (d, 6H, J=7.0 Hz), 1.25 (s, 6H).