Name: 41162-19-0|Dimethyl (2-oxo-4-phenylbutyl)phosphonate|95%
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SKU: A477489
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1
[ 41162-19-0 ]
[ 104596-33-0 ]
(Z)-7-[(1S,2R,3S,4R)-3-((E)-3-Oxo-5-phenyl-pent-1-enyl)-7-oxa-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride 1.) DME, 2.) 23 deg C; Multistep reaction;

Reference： [1]Das; Hall; Nakane; Haslanger; Reid; Garber; Truc; Harris; Hedberg; Ogletree [Journal of Medicinal Chemistry, 1990, vol. 33, # 6, p. 1741 - 1748]

2
[ 41162-19-0 ]
<1α,2β(5Z),3β,4α>-7-<5,6-exo-epoxy-3-formyl-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoic acid methyl ester [ No CAS ]
(Z)-7-[(1S,2S,4R,5R,6R,7S)-7-((E)-3-Oxo-5-phenyl-pent-1-enyl)-3,8-dioxa-tricyclo[3.2.1.0^2,4]oct-6-yl]-hept-5-enoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; lithium bromide 1.) CH₂Cl₂, 25 deg C, 15 min, 2.) 25 deg C, overnight; Multistep reaction;

Reference： [1]Das, Jagabandhu; Vu, Truc; Harris, Don N.; Ogletree, Martin L. [Journal of Medicinal Chemistry, 1988, vol. 31, # 5, p. 930 - 935]

3
[ 41162-19-0 ]
[ 38754-71-1 ]
[ 41639-72-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In isopropyl alcohol at 25℃; for 0.5h; Stage #2: (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate In isopropyl alcohol at 25℃; for 5h;	2 Example 2: Manufacture of (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-5-phenylpent-1-enyl)hexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate. Dimethyl 2-oxo-4-phenylbutylphosphonate (0.4 g, 1.43 mmol, 1 eq) was added to a 100 ml 3-neck flask and 10 ml of i-PrOH (IPA) was added and stirred. K2CO3 (0.6 g, 4.29 mmol, 3 eq) was added and stirred at 25 ° C for 30 minutes. Corey lactone aldehyde (0.5 g, 1.43 mmol, 1 eq) was added and stirred at 25 ° C for 3 hours. The reaction was warmed to 25 and stirred for 2 hours (TLC confirmed completion of the reaction, ethyl acetate (EA): hexane (Hx) = 1: 1, rf = 0.65). The reaction was concentrated under reduced pressure (bath 40 ° C). To the reaction were added 10 ml of water and 10 ml of methylene chloride (MC) and the layers were separated. The water layer was added with 10 ml of MC and extracted one more time. NaCl aqueous solution, and the mixture was dried over Na2SO4, filtered, concentrated under reduced pressure A solid compound was obtained.- 0.61g (yield: 91%). 1H NMR (400MHz, CDCl3): δ2.30 (d, J = 15.6 Hz, 2H), 2.51 (t, J = 11.8 Hz, 1H), 2.67 - 2.56 (m, 1H), 2.91 (dd , J = 18.3, 7.1 Hz, 6H), 5.10 (s, 1H), 5.31 (d, J = 4.9 Hz, 1H), 6.22 (d, J = 15.8 Hz, 1H, CH = CH), 6.66 (dd, J = 15.8, 7.6 Hz, 1H, CH = CH), 7.16 (dd, J = 14.6, 7.8 Hz, 3H, HAr), 7.16 (dd, J = 14.6, 7.8 Hz, 3H, HAr), 7.25 (t, J = 6.9 Hz, 2H, HAr), 7.43 (dt, J = 14.5, 7.6 Hz, 3H, HAr), 7.63 (dd, J = 19.0, 7.2 Hz, 4H, HAr), 8.09 - 8.01 (m, 2H, HAr).
75%	With sodium hydroxide In dichloromethane; water stereoselective reaction;
70%	With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃;	A Compound 1 was synthesized from Corey's lactone 4. The primary alcohol of lactone 4 was oxidized to aldehyde 5 with DCC, DMSO and H3PO4 in DME. The crude aldehyde 5 was reacted with dimethyl (2-oxo-4-phenylbutyl) phosphonate in the presence of lithium chloride and diisopropyl ethyl amine to give 6 in 70% yield. Stereoselective reduction of the enone 6 with S-Alphine hydride in THF at -78° C. provided 70-75% of the (15S)-7 isomer over the (15R)-7 isomer. Alternatively, the reduction could be performed with NaBH4.CeCl4(H2O)7 in MeOH/CH2Cl2 with lower selectivity. The epimers were readily separated by column chromatography on silica gel using tolene:ethyl acetate 2:1 as eluent to give pure (15-S)-7. Removal of the p-phenylbenzoyl (PPB) protective group with K2CO3 in MeOH afforded an 80% yield of the diol 8. The product 8 was purified by column chromatography on silica gel using ethyl acetate as eluent. The free hydroxyl groups of 8 were protected with tetrahydropyranyl (THP) groups to give 9 in quantitative yield. Compound 9 was treated with diisobutylaluminium hydride (DIBAL-H) in dry THF to give the lactol 10. Product 10 underwent Wittig reaction with 4-carboxybutyl-triphenylphosphonium bromide, t-BuOK in dry THF affording the acid 11. This was further reacted without isolation with isopropyl iodide in the presence of DBU in acetone to give the corresponding ester 12, which was isolated by column chromatography on silica gel using ethyl acetate:hexane 1:1. Compound 12 was oxidized with pyridinium chlorchromate treated with aluminium oxide (PCC/Al2O3) in dichloromethane to give the compound 13. The protecting groups 11, 15-bistetrahydro-pyranyloxy groups were removed by addition of 1N HCl in acetonitrile. The reaction mixture was stirred at room temperature for about 3 hrs to give 14. This was further reacted without isolation with addition of excess 1N HCl. The mixture was stirred for additional 40 hrs to accomplish quantitative conversion to the corresponding PGA2 ester analogue (1).

	With sodium hydride 1.) THF, 90 min, 2.) THF, 30 min; Multistep reaction;
	With sodium hydroxide In dichloromethane; water at 0 - 5℃; for 1.5h;	1 A solution of (-)-Corey lactone 5-(4-phenylbenzoate) 9 (17.6 g, 50.0 mmol) and TEMPO (0.16 g, 1.0 mmol) in CH2Cl2 (100 mL) was added to a solution of NaBr (0.5 g, 5.0 mmol), NaHCO3 (12.6 g, 150.0 mmol) and IPA (6.0 g, 100.0 mmol) in water (100 mL). 5% aq. NaOCl (about 150 mL) was added dropwise to the stirred mixture at -5 to 0° C. until disappearance of Corey lactone (TLC monitoring). The obtained mixture was stirred for 0.5 h at the same temperature. The aqueous layer was separated and extracted with CH2Cl2 (50 mL). The combined organic layers was added dropwise over 1 h to a stirred mixture of a solution of BnCH2COCH2PO(OMe)2 (15.4 g, 60.0 mmol) in CH2Cl2 (20 mL) and 30% NaOH (8.0 g, 60.0 mmol) at 0-5° C. The mixture was stirred 0.5 h at the same temperature and treated with 10% aq. citric acid (100 mL). The aqueous layer was separated and extracted with CH2Cl2 (50 mL). The combined organic layers were dried over Na2SO4, filtered through short silica gel column and concentrated in vacuo. The oily residue (24.2 g) was dissolved in refluxed EtOH (150 mL) and cooled in ice bath. The precipitate was filtered off, washed with cold EtOH and dried in vacuo to give 20.1 g (84%) of ketone 7 with 99.4% purity by HPLC: mp 129-130° C., [α]20D-142° (c 1.0, CHCl3); 1H NMR (CDCl3) 2.32-2.63 (m, 3H); 2.84-2.97 (m, 7H); 5.00-5.10 (m, 1H); 5.20-5.35 (m, 1H); 6.20 (d, J=16 Hz, 1H); 6.65 (dd, J=16 and 8 Hz, 1H); 7.15-7.67 (m, 12H); 8.03 (d, J=8 Hz, 2H).

Reference： [1]Current Patent Assignee: MIRAE FINE CHEMICAL CO LTD - KR2016/15100, 2016, A Location in patent: Paragraph 0078-0081
[2]Chen, Fener; Huang, Zedu; Jiang, Meifen; Li, Weijian; Tang, Pei; Ye, Baijun; Zhang, Guo-Tai; Zhu, Kejie [Chemical Science, 2021, vol. 12, # 30, p. 10362 - 10370]
[3]Current Patent Assignee: SYNPHORA - US2006/41016, 2006, A1 Location in patent: Page/Page column 4
[4]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]
[5]Current Patent Assignee: OPKO HEALTH INC - US2009/163596, 2009, A1 Location in patent: Page/Page column 10

4
[ 104-53-0 ]
[ 41162-19-0 ]
[ 79559-59-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; for 0.666667h; Inert atmosphere; Stage #2: 3-phenyl-propionaldehyde at 40℃; for 12h;
	With potassium hexamethylsilazane Multistep reaction;

Reference： [1]Wang, Congcong; Zhang, Yu-Fang; Guo, Shimeng; Zhao, Quan; Zeng, Yanping; Xie, Zhicheng; Xie, Xin; Lu, Boxun; Hu, Youhong [Journal of Medicinal Chemistry, 2021, vol. 64, # 2, p. 941 - 957]
[2]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

5
[ 2021-28-5 ]
[ 756-79-6 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With n-butyllithium; diisopropylamine In tetrahydrofuran at 5 - 20℃; Inert atmosphere;	General method for the preparation of Horner-Wadsworth-Emmons reagents:Dimethyl 2-oxo-2-phenylethylphosphonate (9a) General procedure: To a 200 mL flame-dried three-necked flask under argon atmosphere wereintroduced 42.6 mL of BuLi (1.55 M, 66.0 mmol) and 9.7 mL of THF so as to controlthe concentration to ca 1 M, where 1,1,1,3,3,3-hexamethyldisilazane (14.0 mL, 66.0mmol) was added slowly and stirring was continued for 15 min at room temperature.Dimethyl methylphosphonate (3.6 mL, 33 mmol) was added with keeping thetemperature inside and then, ethyl benzoate (4.3 mL, 30 mmol) was added at lower than5 °C. When complete consumption of ethyl benzoate was confirmed by TLC, thereaction mixture was quenched with water and extracted three times with AcOEt. The combined AcOEt phase was further washed with water and brine successively, and driedover anhydrous Na2SO4. After filtration, evaporation of the volatiles afforded thecrude material which was purified by silica gel column chromatography using AcOEt asan eluent to furnish 6.8 g of the title compound, dimethyl 2-oxo-2-phenylethylphosphonate 9a was obtained (29.7 mmol, 99% yield) as a color- less oil.
	With n-butyllithium 1.) THF, -78 deg C, 15 min, 2.) THF, -78 deg C, 30 min; Multistep reaction;
	With n-butyllithium In tetrahydrofuran; diethyl ether; hexane; water; acetic acid	9.iv (iv) (iv) Preparation of dimethyl 2-oxo-ω-phenylalkylphosphonates A solution of butyl lithium (9.6 g.) in hexane (97 ml.) and anhydrous diethyl ether (160 ml.) was added during 20 minutes to a stirred solution of dimethyl methylphosphonate (18.6 g.) in anhydrous tetrahydrofuran (80 ml.) at -50° C, in an atmosphere of nitrogen. The solution was stirred for a further 15 minutes at -60° C, and then a solution of ethyl β-phenylpropionate (13.4 g.) in anhydrous tetrahydrofuran (60 ml.) was added during 10 minutes at -60° C. This solution was stirred at -60° C, for 90 minutes and then at the ambient temperature for 150 minutes. Glacial acetic acid (14.2 ml.) was then added and the solvents were evaporated off. Water (75 ml.) was added to the gelatinous residue and then the mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and the ether was then removed in vacuo. The residue was distilled, to give dimethyl 2-oxo-4-phenylbutylphosphonate (10.7 g.) in the form of a colourless oil, b.p. 155°-158° C./0.1 mm.Hg. (Elemental analysis: C, 56.4; H, 6.9; P, 11.8%; C12 H17 O4 P requires: C, 56.25; H, 6.7; P, 12.1%; νmax 835 cm-1, 1035 cm-1, 1180 cm-1, 1260 cm-1, 1455 cm-1, 1710 cm-1).

	Stage #1: dimethyl methane phosphonate With n-hexyllithium In tetrahydrofuran; hexane at -80℃; Inert atmosphere; Stage #2: ethyl dihydrocinnamate In tetrahydrofuran; hexane at 20℃; Inert atmosphere; Stage #3: With water In tetrahydrofuran; hexane at 20℃;	1 Example 1: (2-oxo-4-phenyl-butyl)-phosphonic acid dimethyl ester (19a; R3= Me, W = - CH2CH2Ph); To a solution of 68g of methyl-phosphonic-acid dimethyl ester (MW = 124.8; 1.6 eq.) in 325mL of THF was added 218mL of n-hexyllithium (2.5M in hexane; 1.6 eq.) at -80°C. The mixture was stirred for 30min and a solution of 60g of ethyl-3-phenyl propionate (MW = 178.23, d = 1.01, 1.0 eq.) in 90mL of THF was added. The mixture was allowed to warm to ambient temperature and 150mL of water were added. After separation of the layers the organic layer was extracted twice with water. The pH value of the combined aqueous layers was adjusted pH = 2 with 5M HCl and then extracted twice with DCM. Removal of the organic solvents under reduced pressure gave 89g of the title compound (Assay: 86.8%; Yield = 89.7%). It is not necessary to dry to completion, a 50 w% solution in MED is also suitable for the next step.
	With n-butyllithium In tetrahydrofuran; hexane	13.B Step B. Step B. Preparation of Dimethyl 2-Oxo-4-phenylbutylphosphonate A solution of dimethyl methylphosphonate (12.4 g., 0.1 mole) in dry tetrahydrofuran (75 ml.) is stirred, maintained under a nitrogen atmosphere, cooled to -50° C., and treated with a 2 N solution of n-butyl lithium in hexane (50 ml., 0.1 mole) added dropwise. Upon completing the addition, the reaction mixture is kept at -50° C. for 1/2 hour to ensure anion formation and then is treated with ethyl 3-phenylpropionate (8.9 g., 0.05 mole) added dropwise at -50° C. After stirring for an additional 11/2 hours at -50° to -40° C., the reaction mixture is poured into ice water (250 ml.) providing a turbid solution which is acidified with 2 N hydrochloric acid and extracted with ethyl acetate (4 * 75 ml.). The combined organic extract is dried over sodium sulfate and filtered. Evaporation of the filtrate in vacuo at 40° to 50° C. leaves an oily residue which is distilled to provide the title compound as an oil (11.0 g., 86%), b.p. 148°-150° C./0.1 mm.

Reference： [1]Hamada, Yoko; Kawasaki-Takasuka, Tomoko; Yamazaki, Takashi [Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1507 - 1512]
[2]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]
[3]Current Patent Assignee: SANOFI - US4088695, 1978, A
[4]Current Patent Assignee: Sandoz (in: Novartis); NOVARTIS AG - EP2143712, 2010, A1 Location in patent: Page/Page column 52-53
[5]Current Patent Assignee: MERCK & CO INC - US4059587, 1977, A

6
[ 41162-19-0 ]
[ 39746-01-5 ]
[ 55076-60-3 ]

Yield	Reaction Conditions	Operation in experiment
84.7%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In acetonitrile at -15℃;	2 To a suspension of 21g of LiCl (MW = 42.39; 4.4 eq.) in 280mL of acetonitrile was added 37g of compound 19a (MW = 256.25; 1.3 eq.; prepared as described in example 1). The resulting mixture is cooled to -15°C and 45mL of Hünig's base (MW = 129.25; d =0.755; 3.0 eq.) were added. After stirring for 1h at -15°C 520mL of the benzoyl protected Corey aldehyde solution obtained as described above were added. After stirring for 1 h 19mL of glacial acetic acid were added before the reaction mixture was warmed to ambient temperature. The reaction mixture was washed consecutively with an aqueous NaCl solution (18%) and water. Then the main part of the organic solvents were removed by distillation under reduced pressure and pre-warmed (80°C) ethanol (96%) was added. Then the mixture was distilled under reduced pressure until the desired product started to crystallize from the mixture. The crystals were collected by filtration after cooling the suspension to 0°C and washed twice an ice-cold mixture of ethanol / water (1 / 1) to yield 38g of the title compound after drying (40°C, 10mbar; yield = 84.7%; assay: 99.2%). [Show Image] 1H-NMR (CDCl3, 300MHz) δ(ppm) = 2.35 (dd, CH2, 1 H, J 10.6Hz, J 3.1 Hz), 2.60 (m, CH2, 3H), 2.90 (m, CH, CH2, 5H), 5.09 (dt, CH, 1 H, J 4.3Hz, 1.8Hz), 5.33 (q, CH, 1H, J 5.5Hz), 6.25 (d, CH, 1H, 16.4Hz), 6.70 (m, CH, 1H), 7.25 (m, CH, 5H), 7.49 (m, CH, 2H), 7.61 (m, CH, 1 H), 8.02(m, CH, 2H). 13C-NMR (CDCl3, 75.47MHz) δ(ppm) = 30.37, 35.28, 38.23, 42.87, 42.95, 54.43, 78.89, 83.54, 126.64, 128.81, 128.95, 129.01, 129.64, 130.11, 131.86, 133.96, 141.29, 143.48, 166.28, 176.26, 199.06.
73%	With triethylamine; lithium chloride In tetrahydrofuran; dichloromethane at 0℃; for 2h; Cooling with ice;	1 A solution of 1,3-diisopropylcarbodiimide (13.7 g) in dimethyl sulfoxide (38 mL) contained in a nitrogen-substituted flask was added dropwise with a solution of [3aR-(3aα ,4α ,5α ,6a α)]-5-(benzoyloxy)hexahydro-4-(hydroxymethyl)-2H-cyclopenta[b]furan-2-one [compound of the formula (II) (X is benzoyl), 14.9 g] and orthophosphoric acid (1.1 g) in dimethyl sulfoxide. The mixture was stirred at about 30°C for 2 hours, and then added with methylene chloride, and the deposited white solid was removed by filtration. The filtrate was washed with water, dried over magnesium sulfate, then filtered, and concentrated to obtain 23.2 g of an aldehyde compound. A solution of dimethyl (2-oxo-4-phenylbutyl)phosphonate (18.0 g) in tetrahydrofuran was added with lithium chloride (3.0 g) and triethylamine (7.1 g) and stirred. The mixture was added dropwise with a solution of the aldehyde obtained in the previous reaction in methylene chloride (90 mL) under ice cooling, and stirred for 2 hours. After completion of the reaction, the reaction mixture was adjusted to about pH 2 with 2 M hydrochloric acid, and added with water, and the layers were separated. The organic layer was dried over magnesium sulfate, filtered, and concentrated to obtain a crude product. The resulting crude product was subjected to silica gel column chromatography (ethyl acetate/hexane = 1/2 → ethyl acetate), and crystals deposited after evaporation of the solvent were collected by filtration, and dried to obtain 15.9 g of a product (yield: 73%). NMR δ 5.07 (m, 1H), 5.28 (m, 1H), 6.20 (d, 1H), 6.65 (dd, 1H), 7.16-7.30 (m, 5H), 7.42-7.47 (m, 2H), 7.55-7.60 (m, 1H), 7.96-8.00 (m, 2H)
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hexamethyldisilazane In 1,2-dimethoxyethane Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In 1,2-dimethoxyethane

	With n-butyllithium In tetrahydrofuran; hexane; dichloromethane; acetic acid	2.a 2(a) 2(a) (1S,5R,6R,7R)-6-[(E)-3-Oxo-5-phenyl-1-pentenyl]-7-benzoyloxy-2-oxabicyclo[3,3,0]octan-3-one At 20° under argon, 20 ml. of a 2-molar butyllithium solution in hexane was added dropwise to a solution of 11.2 g. of dimethyl-2-oxo-4-phenylbutylphosphonate in 400 ml. of ether. The mixture was stirred for 5 minutes and then 600 ml. of ether was added thereto and the mixture again stirred for 5 minutes at 20°. Thereafter, a solution of 9.26 g. of (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3,3,0]octan-3-one [J. Amer. Chem. Soc. 96, 5865 (1974)] in 150 ml. of tetrahydrofuran was added dropwise to this mixture, and the latter was agitated for 30 minutes at 20°. 6 ml. of glacial acetic acid was added thereto, and the mixture was evaporated under vacuum. The residue was taken up in 600 ml. of methylene chloride, shaken twice with respectively 100 ml. of saturated sodium bicarbonate solution, twice with respectively 100 ml. of water, dried over magnesium sulfate, and evaporated under vacuum. After recrystallization from isopropyl ether/methylene chloride, 11 g. of the title compound was obtained as colorless crystals; m.p. 119°-120°.
	With triethylamine; lithium chloride In dichloromethane at 0℃; for 2h;	1 Example 1 Synthesis of [3aR-(3aα,4α,5α,6aα)]-hexahydro-2-oxo-4-(5-phenyl-3-oxopent-1-phenyl)-5-benzoyloxy-2H-cyclopenta[b]furan [compound of the formula (IV) wherein X is benzoyl Group] A solution of 1,3-diisopropylcarbodiimide (13.7 g) in dimethyl sulfoxide (38 mL) contained in a nitrogen-substituted flask was added dropwise with a solution of [3aR-(3aα,4α,5α,6aα)]-5-(benzoyloxy)hexahydro-4-(hydroxymethyl)-2H-cyclopenta[b]furan-2-one [compound of the formula (II) (X is benzoyl), 14.9 g] and orthophosphoric acid (1.1 g) in dimethyl sulfoxide. The mixture was stirred at about 30° C. for 2 hours, and then added with methylene chloride, and the deposited white solid was removed by filtration. The filtrate washed with water, dried over magnesium sulfate, then filtered, and concentrated to obtain 23.2 g of an aldehyde compound. A solution of dimethyl (2-oxo-4-phenylbutyl)phosphonate (18.0 g) in tetrahydrofuran was added with lithium chloride (3.0 g) and triethylamine (7.1 g) and stirred. The mixture was added dropwise with a solution of the aldehyde obtained in the previous reaction in methylene chloride (90 mL) under ice cooling, and stirred for 2 hours. After completion of the reaction, the reaction mixture was adjusted to about pH 2 with 2 M hydrochloric acid, and added with water, and the layers were separated. The organic layer was dried over magnesium sulfate, filtered, and concentrated to obtain a crude product. The resulting crude product was subjected to silica gel column chromatography (ethyl acetate/hexane=1/2→ethyl acetate), and crystals deposited after evaporation of the solvent were collected by filtration, and dried to obtain 15.9 g of a product (yield: 73%). NMR δ 5.07 (m, 1H), 5.28 (m, 1H), 6.20 (d, 1H), 6.65 (dd, 1H), 7.16-7.30 (m, 5H), 7.42-7.47 (m, 2H), 7.55-7.60 (m, 1H), 7.96-8.00 (m, 2H)

Reference： [1]Current Patent Assignee: Sandoz (in: Novartis); NOVARTIS AG - EP2143712, 2010, A1 Location in patent: Page/Page column 53-54
[2]Current Patent Assignee: KIRIN HOLDINGS CO., LTD. - EP1886992, 2008, A1 Location in patent: Page/Page column 8
[3]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]
[4]Current Patent Assignee: BAYER AG - US4346228, 1982, A
[5]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - US2008/33176, 2008, A1 Location in patent: Page/Page column 5-6

7
[ 103-25-3 ]
[ 756-79-6 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 3-phenylpropanoic acid methyl ester In tetrahydrofuran at -78℃; for 1h;	1.b Step b Under the protection of N2, dissolve dimethyl methylphosphonate (1.3mL, 12.2mmol) in dry THF (15mL), cool to -78°C, and add n-BuLi solution (2.4M in THF, 5.6mL ), after stirring at -78°C for 30 min, a tetrahydrofuran solution (5 mL) of methyl 3-phenylpropionate 1-2 (1.0 g, 6.1 mmol) was added and stirred at -78°C for 1 h, TLC monitored the reaction to be complete. It was quenched by adding saturated NH4C1 solution at 0C. Ethyl acetate (50 mL) and water (50 mL) were added to the reaction system, and the organic layer was washed with water (50 mL) and saturated brine (50 mL) in this order. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product, which was separated and purified by column chromatography (DCM:MeOH=100:0~95:5) to obtain a colorless oily liquid 1-4 (1.5g, yield 98%).
98%	With n-butyllithium In tetrahydrofuran at -78 - 0℃; Inert atmosphere;
97%	Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: 3-phenylpropanoic acid methyl ester In tetrahydrofuran; hexane at -78 - 0℃;

97%	With lithium diisopropyl amide In tetrahydrofuran; hexane at 0℃; for 2h;
90%	Stage #1: 3-phenylpropanoic acid methyl ester; dimethyl methane phosphonate With lithium diisopropyl amide In tetrahydrofuran at -5 - 0℃; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; water
	Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran at 0℃; Stage #2: 3-phenylpropanoic acid methyl ester In tetrahydrofuran
	With n-butyllithium; acetic acid In tetrahydrofuran; hexane; water	R.64 Dimethyl 2-oxo-4-phenylbutylphosphonate (64) STR83 REFERENCE EXAMPLE 64 Dimethyl 2-oxo-4-phenylbutylphosphonate (64) STR83 To a stirred solution of dimethyl methylphosphonate (8.85 g, 0.071 mol) in 150 ml of anhydrous THF at -78° C. was added dropwise a solution of n-butyl lithium in hexane (1.67N, 43.1 ml, 0.072 mol) under argon atmosphere, and the mixture was stirred for 30 minutes. To this reaction solution was added methyl 3-phenylpropionate (5.0 g, 0.030 mol) in 10 ml of anhydrous THF. After being stirred for 30 minutes, the reaction mixture was allowed to warm to 0° C., diluted with 5.5 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue and the mixture was extracted with ethyl acetate (100 ml*2). The combined organic layers were washed with water (20 ml) and brine (20 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give a colorless transparent oil of dimethyl 2-oxo-4-phenylbutylphosphonate (7.39 g, 0.029 mol, yield 96%, b.p. 104°-105° C./0.23 mmHg). IR(Liquid film method): 3050, 3020, 2940, 2840, 1705, 1595, 1485, 1445, 1395, 1360, 1250, 1170, 1025, 885, 840, 810, 740, 690 cm-1. NMR(90 MHz, CDCl3): 2.93(4H, broad s), 3.07(2H, d, J=22.9 Hz), 3.74(6H, J=11.2 Hz), 7.0-7.4(5H, m).
	Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: 3-phenylpropanoic acid methyl ester In tetrahydrofuran Inert atmosphere;
	With n-butyllithium In tetrahydrofuran

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; FUDAN UNIVERSITY; Shanghai Institute of Materia Medica (in: CAS) - CN111792990, 2020, A Location in patent: Paragraph 0070-0071; 0074-0075
[2]Wang, Congcong; Zhang, Yu-Fang; Guo, Shimeng; Zhao, Quan; Zeng, Yanping; Xie, Zhicheng; Xie, Xin; Lu, Boxun; Hu, Youhong [Journal of Medicinal Chemistry, 2021, vol. 64, # 2, p. 941 - 957]
[3]Kirsch, Stefan F.; Klahn, Philipp; Menz, Helge [Synthesis, 2011, # 22, p. 3592 - 3603]
[4]Sivák, Ivan; Toběrný, Michal; Kyselicová, Andrea; Caletková, Ol'Ga; Berkeš, Dušan; Jakubec, Pavol; Kolarovič, Andrej [Journal of Organic Chemistry, 2018, vol. 83, # 24, p. 15541 - 15548]
[5]Maloney, Kevin M.; Chung, John Y. L. [Journal of Organic Chemistry, 2009, vol. 74, # 19, p. 7574 - 7576]
[6]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]
[7]Current Patent Assignee: TORAY INDUSTRIES INC - US4775692, 1988, A
[8]Location in patent: scheme or table Cini, Elena; Bifulco, Giuseppe; Menchi, Gloria; Rodriquez, Manuela; Taddei, Maurizio [European Journal of Organic Chemistry, 2012, # 11, p. 2133 - 2141]
[9]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]

8
[ 41162-19-0 ]
[ 346672-53-5 ]
7-[(R)-2-Oxo-5-((E)-3-oxo-5-phenyl-pent-1-enyl)-pyrrolidin-1-yl]-heptanoic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In 1,2-dimethoxyethane at 0℃; Stage #2: ethyl (R)-7-(2-formyl-5-oxopyrrolidin-1-yl)heptanoate In 1,2-dimethoxyethane at 20℃;

Reference： [1]Billot, Xavier; Chateauneuf, Anne; Chauret, Nathalie; Denis, Danielle; Greig, Gillian; Mathieu, Marie-Claude; Metters, Kathleen M.; Slipetz, Deborah M.; Young, Robert N. [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 6, p. 1129 - 1132]

9
[ 140-10-3 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: H₂ / 5 percent Pd/C / ethyl acetate 2.1: MeOH 3.1: N-BuLi / tetrahydrofuran / 0 °C 3.2: tetrahydrofuran

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]

10
[ 41162-19-0 ]
[ 41639-74-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran 3.1: K₂CO₃; MeOH
	Multi-step reaction with 3 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]
[2]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

11
[ 41162-19-0 ]
[ 69610-63-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran 3.1: K₂CO₃; MeOH 4.1: p-TSA / CH₂Cl₂
	Multi-step reaction with 4 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h 4: p-toluenesulfonic acid / CH₂Cl₂ / 0.5 h

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]
[2]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

12
[ 41162-19-0 ]
[ 55444-68-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]

13
[ 41162-19-0 ]
(Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-hept-5-enoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran 3.1: K₂CO₃; MeOH 4.1: p-TSA / CH₂Cl₂ 5.1: DIBAL-H / -78 °C 6.1: NaHMDS 7.1: aq. AcOH / tetrahydrofuran

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]

14
[ 41162-19-0 ]
7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((R)-3-hydroxy-5-phenyl-pentyl)-cyclopentyl]-heptanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran 3.1: K₂CO₃; MeOH 4.1: p-TSA / CH₂Cl₂ 5.1: DIBAL-H / -78 °C 6.1: NaHMDS 7.1: aq. AcOH / tetrahydrofuran 8.1: H₂ / 5 percent Pd/C / ethyl acetate

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]

15
[ 41162-19-0 ]
[(1R,2R,3R,5S)-5-Hydroxy-2-[(E)-(S)-5-phenyl-3-(tetrahydro-pyran-2-yloxy)-pent-1-enyl]-3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-acetaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran 3.1: K₂CO₃; MeOH 4.1: p-TSA / CH₂Cl₂ 5.1: DIBAL-H / -78 °C

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]

16
[ 41162-19-0 ]
7-((1R,2R,3R,5S)-5-hydroxy-2-((3S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy)pent-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)hept-5-enoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH₄ / tetrahydrofuran 3.1: K₂CO₃; MeOH 4.1: p-TSA / CH₂Cl₂ 5.1: DIBAL-H / -78 °C 6.1: NaHMDS

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]

17
[ 501-52-0 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: MeOH 2.1: N-BuLi / tetrahydrofuran / 0 °C 2.2: tetrahydrofuran
	Multi-step reaction with 2 steps 1: sulfuric acid 2: n-butyllithium / tetrahydrofuran
	Multi-step reaction with 2 steps 1.1: sulfuric acid / 2 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C

Multi-step reaction with 2 steps 1: sulfuric acid / 2 h / Reflux 2: n-butyllithium / tetrahydrofuran / -78 - 0 °C / Inert atmosphere

Reference： [1]DeLong, Mitchell A.; Amburgey, Jack; Taylor, Cynthia; Wos, John A.; Soper, David L.; Wang, Yili; Hicks, Renee [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522]
[2]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]
[3]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; FUDAN UNIVERSITY; Shanghai Institute of Materia Medica (in: CAS) - CN111792990, 2020, A
[4]Wang, Congcong; Zhang, Yu-Fang; Guo, Shimeng; Zhao, Quan; Zeng, Yanping; Xie, Zhicheng; Xie, Xin; Lu, Boxun; Hu, Youhong [Journal of Medicinal Chemistry, 2021, vol. 64, # 2, p. 941 - 957]

18
[ 41162-19-0 ]
(1R,2R,3R)-2-Methyl-3-(3-phenyl-propionyl)-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

19
[ 41162-19-0 ]
(1S,2S,3S)-2-Pentyl-3-(3-phenyl-propionyl)-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

20
[ 41162-19-0 ]
(1R,2R,3R)-2-(1-Amino-1-carboxy-3-phenyl-propyl)-3-methyl-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C 4: H₂O / ethanol / 6 h / 100 °C 5: 1 N aq. NaOH / 24 h / 150 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

21
[ 41162-19-0 ]
(1R,2R,3R)-2-Phenethyl-3-(3-phenyl-propionyl)-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

22
[ 41162-19-0 ]
(1R,2R,3R)-2-(2,5-Dioxo-4-phenethyl-imidazolidin-4-yl)-3-methyl-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C 4: H₂O / ethanol / 6 h / 100 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

23
[ 41162-19-0 ]
(1S,2S,3S)-2-(1-Amino-1-carboxy-3-phenyl-propyl)-3-pentyl-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C 4: H₂O / ethanol / 6 h / 100 °C 5: 1 N aq. NaOH / 24 h / 150 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

24
[ 41162-19-0 ]
(1S,2S,3S)-2-(1-Amino-1-carboxy-3-phenyl-propyl)-3-phenethyl-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C 4: H₂O / ethanol / 6 h / 100 °C 5: 1 N aq. NaOH / 24 h / 150 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

25
[ 41162-19-0 ]
(1R,2R,3R)-2-(2,5-Dioxo-4-phenethyl-imidazolidin-4-yl)-3-pentyl-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C 4: H₂O / ethanol / 6 h / 100 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

26
[ 41162-19-0 ]
(1S,2S,3S)-2-(2,5-Dioxo-4-phenethyl-imidazolidin-4-yl)-3-phenethyl-cyclopropanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1.) KHMDS 2: 1.) DBU / 1.) CHCl₃, 30 min, 2.) CHCl₃, 2 d 3: 1 N aq. NaOH / ethanol / 60 °C 4: H₂O / ethanol / 6 h / 100 °C

Reference： [1]Collado, Ivan; Ezquerra, Jesus; Mazon, Angel; Pedregal, Concepcion; Yruretagoyena, Belen; Kingston, Anne E.; Tomlinson, Rosemary; Wright, Rebecca A.; Johnson, Bryan G.; Schoepp, Darryle D. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2849 - 2854]

27
[ 41162-19-0 ]
[ 69590-43-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h 4: p-toluenesulfonic acid / CH₂Cl₂ / 0.5 h 5: diisobutylaluminum hydride / toluene; hexane / 0.33 h 6: 1.) sodium methylsulfinylcarbanide / 1.) Me₂SO, 2.) Me₂SO, 2 h 7: Jones reagent / acetone / 0.08 h / -20 °C 8: 65percent aq. acetic acid / 14 h / Ambient temperature

Reference： [1]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

28
[ 41162-19-0 ]
[ 856453-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h 4: p-toluenesulfonic acid / CH₂Cl₂ / 0.5 h 5: diisobutylaluminum hydride / toluene; hexane / 0.33 h

Reference： [1]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

29
[ 41162-19-0 ]
[ 69590-40-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h 4: p-toluenesulfonic acid / CH₂Cl₂ / 0.5 h 5: diisobutylaluminum hydride / toluene; hexane / 0.33 h 6: 1.) sodium methylsulfinylcarbanide / 1.) Me₂SO, 2.) Me₂SO, 2 h

Reference： [1]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

30
[ 41162-19-0 ]
[ 69590-42-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h 4: p-toluenesulfonic acid / CH₂Cl₂ / 0.5 h 5: diisobutylaluminum hydride / toluene; hexane / 0.33 h 6: 1.) sodium methylsulfinylcarbanide / 1.) Me₂SO, 2.) Me₂SO, 2 h 7: Jones reagent / acetone / 0.08 h / -20 °C

Reference： [1]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

31
[ 41162-19-0 ]
[ 41639-23-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h

Reference： [1]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

32
[ 41162-19-0 ]
[ 41639-73-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h

Reference： [1]Schaaf, Thomas K.; Bindra, Jasjit S.; Eggler, James F.; Plattner, Jacob J.; Nelson, A. James; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 11, p. 1353 - 1359]

33
[ 41162-19-0 ]
[ 85873-60-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DME, 2.) 23 deg C 2: aq. LiOH / tetrahydrofuran / 23 °C

Reference： [1]Das; Hall; Nakane; Haslanger; Reid; Garber; Truc; Harris; Hedberg; Ogletree [Journal of Medicinal Chemistry, 1990, vol. 33, # 6, p. 1741 - 1748]

34
[ 41162-19-0 ]
(Z)-7-[(1S,2R,3S,4R)-3-((E)-(S)-3-Hydroxy-5-phenyl-pent-1-enyl)-7-oxa-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DME, 2.) 23 deg C 2: NaBH₄, CeCl₃ / methanol / 0 °C

Reference： [1]Das; Hall; Nakane; Haslanger; Reid; Garber; Truc; Harris; Hedberg; Ogletree [Journal of Medicinal Chemistry, 1990, vol. 33, # 6, p. 1741 - 1748]

35
[ 73548-18-2 ]
[ 41162-19-0 ]
C₂₁H₂₈O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; lithium chloride In tetrahydrofuran	5 Horner-Emmons condensation of enal 21 with phosphonate 24 [commercially available from Fisher Scientific, 1 Reagent Lane, Fair Lawn, N.J., 07410] using NEt3/LiCl in THF provides dienone 25, which is reduced to S alcohol acid 5 (R=H) using (-)-Ipc2BCl in THF at 0° C. Treatment of 5 (R=H) with either diazomethane or ethyl iodide/DBU provides 5 (R=CH3) or 5 (R=C2H5), respectively

Reference： [1]Current Patent Assignee: ALCON, INC. - US2006/128803, 2006, A1 Location in patent: Page/Page column 5

36
argon [ No CAS ]
[ 352276-27-8 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With phosphorous acid trimethyl ester In acetonitrile	1.1.3 1.3) 1.3) Dimethyl (2-oxo-4-phenylbutyl)phosphonate A 0.5 L four necked flask equipped with condenser connected to bubbler, thermometer, dropping funnel with pressure equalization arm and deep-tube for bubbling argon through the reaction mixture was charged with a solution of 1-iodo-4-phenyl-2-butanone (89.5 g) in acetonitrile (250 mL). Trimethylphosphite (80.9 g) was added dropwise to the solution, over 1.5 h, with simultaneous bubbling of an argon through the reaction mixture. The temperature of the reaction mixture was allowed to change from 23° C. to 43° C. The resulting mixture was refluxed during 1 h and evaporated under reduced pressure. The residue was fractionally distilled at 0.05 mm Hg to give 71.0 g (85% yield) of dimethyl (2-oxo-4-phenylbutyl)phosphonate, bp 129-130° C./0.05 mm Hg. 1H NMR (CDCl3, δ) 2.88-2.92 (m, 4H); 2.98 (t, J=23 Hz; 2H); 3.68 (s, 3H); 3.74 (s, 3H); 7.14-7.24 (m, 5H).

Reference： [1]Current Patent Assignee: OPKO HEALTH INC - US2003/149294, 2003, A1

37
(R)-hydroxycitronellal [ No CAS ]
[ 41162-19-0 ]
(R)-2-hydroxy-2,6-dimethyl-12-phenyldodec-8-trans-en-10-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With formic acid In tetrahydrofuran; cyclohexane; acetic acid; ethyl acetate	2 Compounds G, H, I, J, K, L, M and N EXAMPLE 2 Compounds G, H, I, J, K, L, M and N A solution of dimethyl 2-oxo-4-phenylbutylphosphonate (1.5 g) in anhydrous tetrahydrofuran (20 ml) was added to a stirred suspension of sodium hydride (0.14 g) in anhydrous tetrahydrofuran (20 ml) in an atmosphere of nitrogen. The mixture was stirred at room temperature for 24 hours and was then treated with a solution of (R)-hydroxycitronellal (1.0 g) in anhydrous tetrahydrofuran (15 ml) and stirred for a further 3 hours in an atmosphere of nitrogen. The pH of the solution was adjusted to 4 by the addition of glacial acetic acid, the solvent was removed in vacuo, and the residue was extracted with diethyl ether. The ethereal solution was washed with water, with aqueous sodium bicarbonate solution (10% w/v), and then with water, dried over magnesium sulphate, and evaporated to leave a residue (1.9 g), a portion of which (0.3 g) was purified by preparative thin layer chromatography on silica gel, using a mixture of ethyl acetate, cyclohexane and 90% w/w formic acid (200:200:5 by volume) as eluant, to give (R)-2-hydroxy-2,6-dimethyl-12-phenyldodec-8-trans-en-10-one (125 mg) in the form of a very pale yellow oil. [elemental analysis: C, 79.6; H, 10.1%. C20 H30 O2 requires C, 79.4; H, 10.0%. νmax 980, 1375, 1625 and 3450 cm-1. NMR (approximately 10% w/v solution in deuterochloroform); multiplets at 1.15-2.3δ and 0.7-1.0δ, doublet of triplets at 6.8δ (J=16 and 6 cycles/second), doublet at 6.05δ (J=16 cycles/second), singlets at 7.2δ and 2.85δ]. By proceeding in a similar manner but replacing the dimethyl 2-oxo-4-phenylbutylphosphonate, used as a starting material, by the appropriate quantities of dimethyl 4-(3-trifluoromethylphenyl)-2-oxobutylphosphonate, dimethyl 2-oxo-3-phenylpropylphosphonate, dimethyl 2-oxoheptylphosphonate, dimethyl 3,3-dimethyl-2-oxoheptylphosphonate, dimethyl 4-(4-chlorophenyl)-2-oxobutylphosphonate, dimethyl 4-(3-chlorophenyl)-2-oxobutylphosphonate, and dimethyl 4-(2-chlorophenyl)-2-oxobutylphosphonate, respectively, there were prepared (R)-12-(3-trifluoromethylphenyl)-2-hydroxy-2,6-dimethyldodec-8-trans-en-10-one [elemental analysis: C, 66.9; H, 7.8%. C21 H29 F3 O2 requires C, 67.3; H, 7.9: λmax 980, 1125, 1165, 1330, 1380, 1625 and 3450 cm-1. NMR (approximately 10% w/v solution in deuterochloroform): multiplets at 6.55-7.25δ, 2.65-3.15δ, 1.15-2.3δ, doublets at 6.1δ (J=16 cycles/second) and 0.9δ (J=5.5 cycles/second), singlet at 7.4δ];

Reference： [1]Current Patent Assignee: SANOFI - US4243683, 1981, A

38
[ 41162-19-0 ]
7-(2-formyl)-4-oxo-3-thiazolidinyl)heptanoic acid [ No CAS ]
[ 65657-33-2 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dimethoxyethane	13.C Step C. Step C. Preparation of 7-[2-(3-Oxo-5-phenyl-1-trans-pentenyl)-4-oxo-3-thiazolidinyl]heptanoic Acid Dimethyl 2-oxo-4-phenylbutylphosphonate (1 molar equivalent) is added dropwise over a 1/2 hour period to a stirred suspension of sodium hydride (2 equivalents) in 1,2-dimethoxyethane maintained at or below 20° C. To the resulting reaction mixture is slowly added 7-(2-formyl)-4-oxo-3-thiazolidinyl)heptanoic acid (1 molar equivalent) with good stirring and cooling (sufficient to maintain a reaction temperature at or below 20° C.). Upon completing this addition, the reaction is stirred at ambient temperature for 1 hour, then heated at reflux for 1/2 hour, cooled to room temperature, and diluted with water. The aqueous mixture is acidified with dilute hydrochloric acid and extracted with ether. The organic extract is dried over sodium sulfate, filtered, and evaporated in vacuo at 40° C. leaving the title compound as an oily residue which is purified chromatographically on silica gel.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US4059587, 1977, A

39
[ 56893-87-9 ]
[ 41162-19-0 ]
6-(7-hydroxyheptyl)-7-(3-oxo-5-phenylpent-1-enyl)-1,4-dioxaspiro[4.4]nonane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; acetic acid	9.b (ii) (b) A solution of dimethyl 2-oxo-4-phenylbutylphosphonate [2.5g; prepared as described hereinafter in Example 9(iv)] in anhydrous tetrahydrofuran (50 ml.) was added to a stirred suspension of sodium hydride (0.24 g.) in tetrahydrofuran (20 ml.). The mixture was stirred at room temperature in an atmosphere of nitrogen for 24 hours, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [2.7 g; prepared as described hereinbefore in Example 1(iv)] in tetrahydrofuran (30 ml.) and stirred for a further 2 hours in an atmosphere of nitrogen. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo and the residue was extracted with diethyl ether. The ethereal solution was washed with aqueous sodium bicarbonate solution (10% w/v) and then with water and dried over anhydrous magnesium sulphate. Evaporation of the solution gave 6-(7-hydroxyheptyl)-7-(3-oxo-5-phenylpent-1-enyl)-1,4-dioxaspiro[4,4] nonane (3.9 g.), in the form of a yellow oil (νmax 955 cm-1, 990 cm-1, 1625 cm-1, 1665 cm-1, 1690 cm-1).

Reference： [1]Current Patent Assignee: SANOFI - US4088695, 1978, A

40
[ 163074-98-4 ]
[ 41162-19-0 ]
C₂₅H₂₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With triethylamine; lithium chloride In tetrahydrofuran at -18 - -10℃; for 25h;	B; 1.B In a 100 ml flaskl containing 0.62 g of anhydrous lithium chloride, the following were added: 20.5 ml of anhydrous tetrahydrofurane (THF), 2.4 g of dimethyl-(2-oxo-4-phenylbutyl)phosphonate (85% purity) and 1 ml of anhydrous triethylamine. After adding ammine, a milky suspension was formed which was placed in an alcohol bath at a temperature of -10°C. To this was added, in the course of 3 h, the Corey's benzoated aldehyde (2 g in 18 ml of THF), and the mixture was left to react for 10 h. Hence, it was placed at a temperature of -18°C for another 12 h. After this time, 15 ml of methyl tert-butyl ether (MTBE) was added and, over 1 hour, the temperature was increased to 20°C. The mixture was transferred to a funnel separator and was extracted with 15 ml of a 38% sodium bisulphate solution. The aqueous phase was discarded and the organic phase was again extracted with a saturated sodium bicarbonate solution. The organic phase was collected in a 100 ml ball and concentrated to a volume of about 6 ml; 25 ml of ethyl acetate was then added and the volume was again reduced until a white precipitate was formed. The precipitate was re-dissolved under heating in the minimum quantity of ethyl acetate and, still in hot conditions, about 10 ml of MTBE was added a little at a time until a slight clouding was obtained. The solution was then left to cool to reach room temperature and then taken to -18°C for 2 h. After discarding the crystallisation waters by decanting, the precipitate was washed with cold MTBE. The product obtained, corresponding to the desired enone (3), was then dried with a weak nitrogen flow (1.85 g yield 65%). 1H NMR (CDCl3, 500 MHz) was in agreement with the literature.

Reference： [1]Current Patent Assignee: TECHNOPHARMA - EP1721894, 2006, A1 Location in patent: Page/Page column 4; 14; 17; 21

41
C₈H₁₀O₄ [ No CAS ]
[ 41162-19-0 ]
(3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: C₈H₁₀O₄; dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In water; acetone at 20℃; for 2h; Stage #2: With hydrogenchloride In water; acetone	The residue is dissolved in water(30ml), acetone(30ml) and 6N HCl(120ml), the reaction mixture was stirred at room temperature for 0.5 hour(TLC monitoring), then the low chain(8g,31.25mmol) was added, the reaction mixture was stirred at room temperature for 2 hours(TLC monitoring), during this 2 hours, keep the PH=9-10 with potassium carbonate.[Para 39] After reaction is finished, adjust the PH=7 by 6NHC1, and the reaction mixture was extracted with ethyl acetate(3χ500ml),The organic layer was washed with water( 100ml) and brine(3χl00ml),the water solution was extracted with ethyl acetate(3xlθθml), the organic layers were collected and dried on sodium sulphate(200g) over night, then filtered, and evaporated in vacuo. The residue was purification by column chromatography on silica gel(500g) and eluted by used an 7:3 mixture of ethyl acetate and hexane. After evaporating the solution, oil (5g) were obtained. Total yield is 14.3%(w/w).

Reference： [1]Current Patent Assignee: EASTAR CHEMICAL - WO2007/41273, 2007, A2 Location in patent: Page/Page column 7-8

42
[ 1092078-92-6 ]
[ 41162-19-0 ]
[ 1092078-93-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran at 20℃; for 1h; Stage #2: C₈H₁₃NO₃ In tetrahydrofuran at 20℃; for 1h;

Reference： [1]Location in patent: body text Born, Stephen; Kobayashi, Yoshihisa [Synlett, 2008, # 16, p. 2479 - 2482]

43
[ 41162-19-0 ]
[ 128948-10-7 ]
C₂₄H₃₄O₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With triethylamine; lithium chloride In tetrahydrofuran at -15 - -5℃; Stage #2: (-)-7α-triethylsilyloxy-6β-formyl-cis-2-oxabicyclo<3.3.0>octan-3-one In tetrahydrofuran for 1h;	1 6.71 g of LiCl and 30 ml of THF were added into a 250 ml three-necked flask, and then the compound of the formula (XII)/THF solution (9.01 g of the compound of the formula (XII) in 40 ml of THF) was added into the mixture. The TEA/THF solution (9.88 ml of TEA in 20 ml of THF) was added into the mixture dropwise under -15-5° C. After the mixture was stirred for 30 min, the compound of the formula (XI)/THF solution (10 g of the compound of the formula (XI) in 40 ml of THF) was added into the mixture. After reaction for 1 hour, TLC was used to ensure the completion of the reaction. When the reaction was completed, 100 ml of water was added into the mixture to stop the reaction under room temperature. Then, 100 ml of ethyl acetate is used for extraction twice. The upper layer was separated, and sodium sulfate was added into the upper layer for dehydration. After the sodium sulfate was filtered out, the filtrate was concentrated under reduced pressure. Then, the concentrated filtrate was applied into column chromatography, and eluted by the eluent (ethyl acetate/hexane=1/4). Finally, 7.44 g of an oil-like product (II-1) was obtained, and the yield of the product (II-1) was 51%.1H NMR (CDCl3):δ: 7.17-7.31 (m, 5H), 6.52-6.60 (dd, 1H), 6.11-6.17 (d, 1H), 4.93-4.94(q, 1H), 4.0-4.02 (q, 1H), 2.29-2.96 (m, 9H), 1.95-2.05 (m, 1H), 0.89-0.94 (t, 9H), 0.51-0.59 (q, 6H)
27.5 g	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With lithium hydroxide monohydrate In tert-butyl methyl ether at 20℃; for 1h; Stage #2: (-)-7α-triethylsilyloxy-6β-formyl-cis-2-oxabicyclo<3.3.0>octan-3-one In tert-butyl methyl ether; water at 5℃; for 0.916667h;	Synthesis of (3aR,4S,5R,6aS)-hexahydro-4,5-ditriethylsilane-4-(methyl)cyclopenta[b]furan-2-one (9) Oxalyl chloride (27 mL, 2.5 mmol) was dischargeddrop wise to a solution of dichloromethane (500 mL)and dimethyl sulphoxide (28.5 mL, 3.5 mmol) at-72°C for 40 min and stirred for 10 min, then slowly addedcompound 8 (50 g, 1 mmol) to the reaction mixtureand stirring continued for 4 h at the same temperature.The reaction mixture was quenched with triethyl amine(100 mL) at -72°C and diluted with water (300 mL). Organic layer was extracted with dichloromethane (500mL), washed with brine solution and dried over anhydrousNa2SO4. After removal of solvent under reducedpressure the resulted crude aldehyde was used for thenext step without further purification. To a solution of compound 6 (32 g, 1 mmol) inmethyl tertiary butyl ether (500 mL) LiOH.H2O (4.9 g,0.95 mmol) was added at room temperature and reactionmixture was stirred for 1 h (solid precipitated).Then aldehyde compound was added to the reactionmixture at 5°C and stirred for another 10 min. Afterthat water (18 mL) was added and stirring continuedfor 45 min. After completion of reaction, the reactionmixture was quenched with water (500 mL) andaqueous layers were extracted with ethyl acetate (500mL). The organic layer washed with brine solutionand dried over anhydrous Na2SO4, evaporated underreduced pressure. The residue was purified by silica gelchromatography with ethyl acetate and hexane (30:70) solution to afford compound 9 as a yellow solid (27.5g, 53.6%). 1H NMR (300 MHz, CDCl3): δ0.55 (q,6H), 0.9 (J=10.8 Hz, t, 9H), 2.0 (m, 1H), 2.3 (m,1H), 2.45 (J=15 Hz, d, 1H), 2.55 (m, 1H), 2.7-3.0(m, 6H), 4.0 (m, 1H), 4.95 (td, 1H), 6.15 (dd,1H), 6.1(q,1H), 7.2 (J=12.6 Hz, t, 3H), 7.3 (J=12.9 Hz, d, 2H).13C NMR (100 MHz, CDCl3): δ4.59 (2C), 4.68, 6.61(3C), 29.90, 31.70, 34.58, 41.72, 42.36, 56.78, 82.62,83.02, 125.81, 127.89, 128.16, 128.29, 128.45, 131.06,145.35, 140.91, 176.17, 198.55.
	With lithium hydroxide monohydrate In tert-butyl methyl ether at 5℃; for 0.75h; Inert atmosphere;

Reference： [1]Current Patent Assignee: EVERLIGHT CHEMICAL INDUSTRIAL CORPORATION - US2009/259066, 2009, A1 Location in patent: Page/Page column 8
[2]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]
[3]Kamidi, Vijendhar; Kale, Pooja; Boodida, Sathyanarayana [Asian Journal of Chemistry, 2017, vol. 29, # 12, p. 2767 - 2770]

44
[ 41162-19-0 ]
[ 88284-48-4 ]
[ 1170736-73-8 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate; 2-(trimethylsilyl)phenyl trifluoromethanesulfonate With cesium fluoride In tetrahydrofuran at 60℃; for 67h; Inert atmosphere; Stage #2: With silica gel In tetrahydrofuran; ethyl acetate

Reference： [1]Liu, Yi-Lin; Liang, Yun; Pi, Shao-Feng; Li, Jin-Heng [Journal of Organic Chemistry, 2009, vol. 74, # 15, p. 5691 - 5694]

45
(S)-1-(2-oxoethyl)but-3-enyl acrylate [ No CAS ]
[ 41162-19-0 ]
(4S,6E)-8-oxo-10-phenyldeca-1,6-dien-4-yl prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium hexamethyldisilazane at 0℃; for 12h;

Reference： [1]Location in patent: scheme or table Mohapatra, Debendra K.; Das, Pragna P.; Sai Reddy; Yadav [Tetrahedron Letters, 2009, vol. 50, # 43, p. 5941 - 5944]

46
[ 64091-14-1 ]
[ 41162-19-0 ]
[ 1240483-13-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran; mineral oil at 0℃;	1 A solution of dimethyl-(2-oxo-4-phenylbutyl)phosphonate (9.72 g, 0.038 moles, 1.08 eq) in tetrahydrofuran (340 mL) is slowly added to a suspension of NaH (60% in weight in mineral oil, 1.46 g, 0.036 moles, 1.04 eq) in tetrahydrofuran (200 mL) cooled to 00C, in a static argon atmosphere. After the additions, the previously milky solution becomes clear, the ice and water bath is removed, and the solution is left under vigorous stirring at room temperature for one hour during which the formation of a white precipitate is observed. After one hour the solution is brought back to 0°C and Corey I aldehyde is added (10 g, 0.035 moles) dissolved in tetrahydrofuran (75 mL), after which the ice bath is removed. After 90 minutes the reaction is complete and to quench it the following are added: acetic acid (2 mL), a saturated solution of ammonium chloride (230 mL), saline solution (150 mL) and water (50 mL); after stirring for a few minutes the phases are separated. The aqueous phase is extracted with AcOEt. The re-combined organic phases are dried on MgSO4, the solid residue is filtered and the solvent is removed at reduced pressure. The product is purified by means of column chromatography (hexane- AcOEt 8:2 v/v). The pure product is obtained as a colourless oil with a yield of 93%.
92%	With triethylamine; lithium chloride In acetonitrile for 2h; Inert atmosphere;	(3R,4R,5R,6S)-5-((tert-butyldimethylsilyl)oxy)-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one(5a) A flame dried round bottom-flask was chargedwith lithium chloride (444 mg, 10.6 mmol) and a stir bar. Under an argon atmosphere at ambient temperature, phosphate 3a (2.5 g, 9.9 mmol) and acetonitrile (200 ml) were added sequentially to the round-bottom flask by syringe. After five minutes TEA (1.5ml, 10.6 mmol) was added by syringe. The reaction was stirred for 10 min at which time a solution of Corey lactone 4 (2.0 g, 7.0 mmol) and acetonitrile (120 ml) were added. The reaction was stirred for 2 h at which time it was judged complete by TLC. The reaction was diluted with ether (50 ml) then washed with NH4Cl (sat., 50 ml),NaHCO3 (sat., 50 ml), and brine (50 ml). The combined aqueous layer was re-extracted with ether (3 x 50 ml). The combined organic layers were dried over MgSO4. The crude mixture was purified by silica gel chromatography (120 g, 30% EtOAc in hexane) to yield enone 5a (2.70 g, 92%) as yellow oil.

Reference： [1]Current Patent Assignee: P&R SPA - WO2010/97672, 2010, A1 Location in patent: Page/Page column 15-16
[2]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]

47
[ 1042989-36-5 ]
[ 41162-19-0 ]
C₃₅H₃₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In tetrahydrofuran at 50℃;

Reference： [1]Location in patent: scheme or table Fujii, Hideaki; Ida, Yoshihiro; Hanamura, Shinichi; Osa, Yumiko; Nemoto, Toru; Nakajima, Mayumi; Hasebe, Ko; Nakao, Kaoru; Mochizuki, Hidenori; Nagase, Hiroshi [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 17, p. 5035 - 5038]

48
(3aR,4R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate [ No CAS ]
[ 41162-19-0 ]
(3aR,4R,6aS)-2-oxo-4-((E)-3-oxo-5-phenylpent-1-enyl)hexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In dichloromethane at 0℃; for 1h; Stage #2: (3aR,4R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate In dichloromethane at 0 - 5℃;	2 Example 2:; Preparation of (3aR,4R,6aS)-2-oxo-4-((E)-3-oxo-5-phenylpent-l- enyl)hexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4- carboxylate(compound-iii); A solution of dimethyl (2-oxo-4-phenylbutyl)phosphonate (34 g) in dichloromethane(l L) was added drop wise at 0° C to a suspension of 60 % sodium hydride(5.7 g) in dichloromethane (1 L). The mixture was stirred at 0° C for one hour. The solution of aldehyde (compound (ii)) (50 g) in dichloromethane prepared in the previous stage was added drop wise to the mixture at 0-5° C. The reaction completion was monitored by TLC. After the reaction completion, , filtered the reaction mass over celite bed and filtrate was washed with water (1 L), saturated sodium chloride solution (1 L). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to residue. The crude brown residue (compound (iii)(65 g) was taken for the next step.

Reference： [1]Current Patent Assignee: BIOCON LIMITED - WO2011/55377, 2011, A1 Location in patent: Page/Page column 26; 30

49
[(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] [ No CAS ]
[ 41162-19-0 ]
[ 1098095-15-8 ]

Yield	Reaction Conditions	Operation in experiment
22 mg	With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; for 1h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Boese, Dietrich; Fernandez, Enrique; Pietruszka, Joerg [Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3463 - 3469]

50
[(R)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] [ No CAS ]
[ 41162-19-0 ]
[ 1225487-37-5 ]

Yield	Reaction Conditions	Operation in experiment
10 mg	With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; for 1h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Boese, Dietrich; Fernandez, Enrique; Pietruszka, Joerg [Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3463 - 3469]

51
[(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] [ No CAS ]
[ 41162-19-0 ]
[ 7646-69-7 ]
(6R)-(4-oxo-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate; sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #2: [(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] In tetrahydrofuran; mineral oil at -78℃; for 1h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Kirsch, Stefan F.; Klahn, Philipp; Menz, Helge [Synthesis, 2011, # 22, p. 3592 - 3603]

52
C₃₀H₃₄O₇ [ No CAS ]
[ 41162-19-0 ]
4-[(Z)-7-isopropoxy-7-oxohept-2-enyl]-5-[(E)-3-oxo-5-phenylpent-1-enyl]cyclopentane-1,3-diyl dibenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In 1,2-dimethoxyethane at -5 - 25℃; Inert atmosphere; Stage #2: C₃₀H₃₄O₇ In 1,2-dimethoxyethane at -5 - 25℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Asian Journal of Chemistry, 2011, vol. 23, # 7, p. 3121 - 3126]

53
[ 41162-19-0 ]
(Z)-7-(3,5-dihydroxy-2-[(E)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl)hept-5-enoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium hydride / 1,2-dimethoxyethane / -5 - 25 °C / Inert atmosphere 1.2: -5 - 25 °C / Inert atmosphere 2.1: sodium tetrahydroborate / methanol / 0 - 25 °C / Inert atmosphere 3.1: potassium carbonate / 5 h / 25 - 30 °C / Inert atmosphere 4.1: lithium hydroxide monohydrate / tetrahydrofuran / 2 h / 25 - 30 °C / Inert atmosphere 4.2: 25 °C / pH 2 / Inert atmosphere

Reference： [1]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Asian Journal of Chemistry, 2011, vol. 23, # 7, p. 3121 - 3126]

54
[ 41162-19-0 ]
(+/-)-13,14-dehydrolatanoprost [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium hydride / 1,2-dimethoxyethane / -5 - 25 °C / Inert atmosphere 1.2: -5 - 25 °C / Inert atmosphere 2.1: sodium tetrahydroborate / methanol / 0 - 25 °C / Inert atmosphere 3.1: potassium carbonate / 5 h / 25 - 30 °C / Inert atmosphere 4.1: lithium hydroxide monohydrate / tetrahydrofuran / 2 h / 25 - 30 °C / Inert atmosphere 4.2: 25 °C / pH 2 / Inert atmosphere 5.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / -5 - 25 °C / Inert atmosphere 5.2: 12 h / 25 °C / Inert atmosphere

Reference： [1]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Asian Journal of Chemistry, 2011, vol. 23, # 7, p. 3121 - 3126]

55
[ 41162-19-0 ]
4-[(E)-3-hydroxy-5-phenylpent-1-enyl]-5-[(Z)-7-isopropoxy-7-oxohept-2-enyl]cyclopentane-1,3-diyl dibenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydride / 1,2-dimethoxyethane / -5 - 25 °C / Inert atmosphere 1.2: -5 - 25 °C / Inert atmosphere 2.1: sodium tetrahydroborate / methanol / 0 - 25 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: sodium hydride / 1,2-dimethoxyethane / 1.25 h / -5 - 25 °C / Inert atmosphere 1.2: 2 h / -5 - 25 °C / Inert atmosphere 2.1: sodium tetrahydroborate / methanol / 0.67 h / 0 - 25 °C / Inert atmosphere

Reference： [1]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Asian Journal of Chemistry, 2011, vol. 23, # 7, p. 3121 - 3126]
[2]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Synthetic Communications, 2012, vol. 42, # 9, p. 1288 - 1305]

56
[ 41162-19-0 ]
[ 1240483-20-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: triethylamine; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 1 h / 20 °C / 760.05 Torr

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1

57
[ 41162-19-0 ]
[ 1240483-21-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: triethylamine; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 1 h / 20 °C / 760.05 Torr 4.1: 1H-imidazole / dichloromethane / 18 h / 20 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1

58
[ 41162-19-0 ]
[ 1240483-22-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: triethylamine; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 1 h / 20 °C / 760.05 Torr 4.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 5.2: -30 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1

59
[ 41162-19-0 ]
[ 130209-82-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: triethylamine; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 1 h / 20 °C / 760.05 Torr 4.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 5.2: -30 °C 6.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 6.2: 3.25 h / 0 - 20 °C 7.1: hydrogenchloride / water; tetrahydrofuran / 18 h / 20 °C 7.2: pH 6.8 / Aqueous phosphate buffer 8.1: Novozym 435 / 18 h / 30 °C
	Multi-step reaction with 8 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C 3.1: triethylamine / dichloromethane / 5 h / 5 - 10 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1 h / -70 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 6 h / 5 °C 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 16 h / 30 °C 7.1: triethylamine / dichloromethane / 6 h / 5 - 10 °C 8.1: acetic acid / water; tetrahydrofuran / 8 h / 30 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1
[2]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

60
[ 64091-14-1 ]
[ 41162-19-0 ]
C₂₄H₃₄O₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran; mineral oil at 0℃; for 1.5h;	1 Example 1Preparation of the Key Intermediate of General Formula (Iv) where R is a Benzyl ResiduePreparation of the Compound III (Scheme I)A solution of dimethyl-(2-oxo-4-phenylbutyl)phosphonate (9.72 g, 0.038 moles, 1.08 eq) in tetrahydrofuran (340 mL) is slowly added to a suspension of NaH (60% in weight in mineral oil, 1.46 g, 0.036 moles, 1.04 eq) in tetrahydrofuran (200 mL) cooled to 0° C., in a static argon atmosphere. After the additions, the previously milky solution becomes clear, the ice and water bath is removed, and the solution is left under vigorous stirring at room temperature for one hour during which the formation of a white precipitate is observed. After one hour the solution is brought back to 0° C. and Corey I aldehyde is added (10 g, 0.035 moles) dissolved in tetrahydrofuran (75 mL), after which the ice bath is removed. After 90 minutes the reaction is complete and to quench it the following are added: acetic acid (2 mL), a saturated solution of ammonium chloride (230 mL), saline solution (150 mL) and water (50 mL); after stirring for a few minutes the phases are separated. The aqueous phase is extracted with AcOEt. The re-combined organic phases are dried on MgSO4, the solid residue is filtered and the solvent is removed at reduced pressure. The product is purified by means of column chromatography (hexane-AcOEt 8:2 v/v). The pure product is obtained as a colourless oil with a yield of 93%.
86%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran at -20℃; Inert atmosphere;	1.3; 2.3 (3) Synthesis of compound 4a Under the protection of argon, to anhydrous THF (100ml) was added β-carbonyl dimethoxybutylphenyl phosphate (13.60g, 60.0mmol, 1.0eq) and potassium carbonate (25.0g, 180mmol, 3.0eq) at room temperature After reacting for 1h, a solution of compound 3 (17.04g, 60mmol, 1eq) in THF (75ml) was added dropwise, reacted at -20°C overnight, concentrated, ethyl acetate (150ml) and water (80ml) were added, the layer was left standing, water The phase was extracted with ethyl acetate (150 ml*2), washed with saturated brine (70 ml), dried over anhydrous sodium sulfate, and concentrated to give white solid compound 4a (19.62 g, 86%).

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1 Location in patent: Page/Page column 7
[2]Current Patent Assignee: GUANGZHOU KAIMO BIOTECHNOLOGY - CN111018766, 2020, A Location in patent: Paragraph 0053-0055; 0062-0064; 0077; 0084-0086

61
(Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyl dibenzoate [ No CAS ]
[ 41162-19-0 ]
4-[(Z)-7-isopropoxy-7-oxohept-2-enyl]-5-[(E)-3-oxo-5-phenylpent-1-enyl]cyclopentane-1,3-diyl dibenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In 1,2-dimethoxyethane at -5 - 25℃; for 1.25h; Inert atmosphere; Stage #2: (Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyl dibenzoate In 1,2-dimethoxyethane at -5 - 25℃; for 2h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Synthetic Communications, 2012, vol. 42, # 9, p. 1288 - 1305]

62
[ 2550-26-7 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: bromine / methanol / 2.83 h / -5 - 20 °C / Inert atmosphere 2: sodium iodide / acetone / 6 h / 20 °C / Inert atmosphere 3: acetonitrile / 2.5 h / 20 °C / Reflux; Inert atmosphere
	Multi-step reaction with 3 steps 1: bromine / methanol / 4 h / 0 - 15 °C 2: sodium iodide / acetone / 12 h 3: acetonitrile / 3 h / 65 °C
	Multi-step reaction with 2 steps 1: bromine; acetic acid / methanol / Inert atmosphere 2: acetonitrile / 3 h / 65 °C / Inert atmosphere

Multi-step reaction with 2 steps 1: iodine; copper(II) oxide / methanol; dichloromethane / 15 h / 42 °C / Inert atmosphere 2: acetonitrile / 3 h / 65 °C / Inert atmosphere

Reference： [1]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Synthetic Communications, 2012, vol. 42, # 9, p. 1288 - 1305]
[2]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]
[3]Kamidi, Vijendhar; Kale, Pooja; Boodida, Sathyanarayana [Asian Journal of Chemistry, 2017, vol. 29, # 12, p. 2767 - 2770]
[4]Kamidi, Vijendhar; Kale, Pooja; Boodida, Sathyanarayana [Asian Journal of Chemistry, 2017, vol. 29, # 12, p. 2767 - 2770]

63
[ 31984-10-8 ]
[ 41162-19-0 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 1288 - 1305
[2]Journal of Chemical Sciences,2015,vol. 127,p. 2023 - 2028

64
[ 41162-19-0 ]
(+/-)-(Z)-methyl 7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((E)-3-hydroxy-5-phenylpent-1-en-1-yl)cyclopentyl)hept-5-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / 1,2-dimethoxyethane / 1.25 h / -5 - 25 °C / Inert atmosphere 1.2: 2 h / -5 - 25 °C / Inert atmosphere 2.1: sodium tetrahydroborate / methanol / 0.67 h / 0 - 25 °C / Inert atmosphere 3.1: potassium carbonate / 5 h / 25 °C / Inert atmosphere

Reference： [1]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Synthetic Communications, 2012, vol. 42, # 9, p. 1288 - 1305]

65
[ 41162-19-0 ]
(+/-)-bimatoprost [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium hydride / 1,2-dimethoxyethane / 1.25 h / -5 - 25 °C / Inert atmosphere 1.2: 2 h / -5 - 25 °C / Inert atmosphere 2.1: sodium tetrahydroborate / methanol / 0.67 h / 0 - 25 °C / Inert atmosphere 3.1: potassium carbonate / 5 h / 25 °C / Inert atmosphere 4.1: water / 12 h / 25 °C

Reference： [1]Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Synthetic Communications, 2012, vol. 42, # 9, p. 1288 - 1305]

66
[ 352276-27-8 ]
[ 121-45-9 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
60%	In acetonitrile at 20℃; for 2.5h; Reflux; Inert atmosphere;

Reference： [1]Location in patent: experimental part Harikrishna; Mohan, H. Rama; Dubey; Shankar; Subbaraju, Gottumukkala V. [Synthetic Communications, 2012, vol. 42, # 9, p. 1288 - 1305]

67
[ 41162-19-0 ]
[ 155206-00-1 ]

Reference： [1]Patent: US2012/16136,2012,A1
[2]Asian Journal of Chemistry,2017,vol. 29,p. 2767 - 2770

68
[ 41162-19-0 ]
[ 41639-83-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: triethylamine; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 1 h / 20 °C / 760.05 Torr 4.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 5.2: -30 °C 6.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 6.2: 3.25 h / 0 - 20 °C 7.1: hydrogenchloride / water; tetrahydrofuran / 18 h / 20 °C 7.2: pH 6.8 / Aqueous phosphate buffer

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1

69
[ 41162-19-0 ]
[ 1240483-15-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: 1H-imidazole / dichloromethane / 18 h / 20 °C
	Multi-step reaction with 3 steps 1: lithium chloride; triethylamine / acetonitrile / 2 h / Inert atmosphere 2: cerium(III) chloride heptahydrate; sodium tetrahydroborate / methanol / 0.17 h / 0 °C 3: 2,6-dimethylpyridine / dichloromethane / 0 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1
[2]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]

70
[ 41162-19-0 ]
[ 1240483-16-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 4.2: -30 °C
	Multi-step reaction with 4 steps 1: lithium chloride; triethylamine / acetonitrile / 2 h / Inert atmosphere 2: cerium(III) chloride heptahydrate; sodium tetrahydroborate / methanol / 0.17 h / 0 °C 3: 2,6-dimethylpyridine / dichloromethane / 0 °C 4: diisobutylaluminium hydride / dichloromethane; toluene / -78 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1
[2]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]

71
[ 41162-19-0 ]
[ 1240483-17-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 4.2: -30 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 5.2: 3.25 h / 0 - 20 °C
	Multi-step reaction with 5 steps 1.1: lithium chloride; triethylamine / acetonitrile / 2 h / Inert atmosphere 2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / methanol / 0.17 h / 0 °C 3.1: 2,6-dimethylpyridine / dichloromethane / 0 °C 4.1: diisobutylaluminium hydride / dichloromethane; toluene / -78 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.67 h / 0 °C 5.2: 20 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1
[2]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]

72
[ 41162-19-0 ]
[ 1240483-18-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 4.2: -30 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 5.2: 3.25 h / 0 - 20 °C 6.1: potassium carbonate / acetone / 18 h / 20 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1

73
[ 41162-19-0 ]
[ 1240483-23-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C 3.1: triethylamine; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 1 h / 20 °C / 760.05 Torr 4.1: 1H-imidazole / dichloromethane / 18 h / 20 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.5 h / -30 °C / Inert atmosphere 5.2: -30 °C 6.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 6.2: 3.25 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1

74
[ 41162-19-0 ]
[ 1240483-14-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 1.5 h / 0 °C 2.1: (-)-diisopinocamphenylborane chloride / n-heptane; tetrahydrofuran / 5 h / -30 - -25 °C / Inert atmosphere 2.2: 10 h / 20 °C
	Multi-step reaction with 2 steps 1: lithium chloride; triethylamine / acetonitrile / 2 h / Inert atmosphere 2: cerium(III) chloride heptahydrate; sodium tetrahydroborate / methanol / 0.17 h / 0 °C

Reference： [1]Current Patent Assignee: P&R SPA - US2012/16136, 2012, A1
[2]Finnegan, David F.; Shelnut, Erin L.; Nikas, Spyros P.; Chiang, Nan; Serhan, Charles N.; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1228 - 1231]

75
[ 41162-19-0 ]
[ 1379764-64-3 ]
(2S,7S)-7-phenethylazepane-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; lithium chloride / acetonitrile / 20 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: 20% palladium hydroxide on charcoal; hydrogen; acetic acid / methanol / 8 h / 20 °C / 4560.31 Torr / Microwave irradiation

Reference： [1]Cini, Elena; Bifulco, Giuseppe; Menchi, Gloria; Rodriquez, Manuela; Taddei, Maurizio [European Journal of Organic Chemistry, 2012, # 11, p. 2133 - 2141]

76
[ 41162-19-0 ]
[ 850209-99-3 ]
[ 1379764-51-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-dibenzylamino-5-oxo-pentanoic acid benzyl ester In acetonitrile at 20℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Cini, Elena; Bifulco, Giuseppe; Menchi, Gloria; Rodriquez, Manuela; Taddei, Maurizio [European Journal of Organic Chemistry, 2012, # 11, p. 2133 - 2141]

77
[(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] [ No CAS ]
[ 41162-19-0 ]
(6R)-(4-oxo-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With sodium hydride In tetrahydrofuran

Reference： [1]Location in patent: scheme or table Nodwell, Matthew B.; Menz, Helge; Kirsch, Stefan F.; Sieber, Stephan A. [ChemBioChem, 2012, vol. 13, # 10, p. 1439 - 1446]

78
[ 41162-19-0 ]
(3aR,4R,5R,6aS)-5-((tert-butyldiphenylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde [ No CAS ]
[ 1395619-06-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With triethylamine; lithium chloride In tetrahydrofuran at -10℃; for 1.5h; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldiphenylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran at -10℃; for 2.41667h; Inert atmosphere;	9 EXAMPLE 9 (3aR,4R,5R,6aS)-5-(tert-butyldiphenylsilyloxy)-4-((E)-3-oxo-5-phenylpent-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-one [Show Image] Dimethyl 2-oxo-4-phenylbutylphosphonate (244.65 g, 0.955 mol) was suspended in tetrahydrofuran (1600 mL) under nitrogen atmosphere. The mixture was cooled to -10°C; lithium chloride (40.47 g, 0.954 mol) and triethylamine (132.5 mL, 96.7 g, 0.955 mol) were added and the mixture was stirred at 10°C for 1.5 hour. Subsequently a solution of (3aR,4R,5R,6aS)-5-(tert-butyldiphenylsilyloxy)-2-oxohexahydro-2H-cyclopenta[b] furan-4-carbaldehyde (142.5 g, 0.350 mol) in tetrahydrofuran (400 mL) was added dropwise over 25 minutes. The system was stirred at -10°C and the reaction appeared to be complete on TLC analysis after 2 hours. Ethyl acetate (850 mL), water (850 mL) and saturated sodium bicarbonate solution (23 mL) were added. After separation of the layers, the aqueous one was extracted with ethyl acetate (850 mL) and the combined organic layers were washed with 0.3 M sulfuric acid solution (1030 mL) and brine (1100 mL). The removal of the organic solvent under reduced pressure afforded the crude product (368.81 g). Purification was made by column chromatography (eluent: n-hexane:ethyl acetate = 2:1); after combining the fractions of interest and removing the solvents under reduced pressure, the title compound was obtained as an oil (137.0 g, 0.254 mol, 72%). 1H-NMR {400 MHz, CDCl3, δ (ppm)}: 7.53-7.64 (m, 4H, Ph), 7.13-7.47 (m, 11H, Ph), 6.31 (dd, J=7.6, 15.6 Hz, 1H, vinyl), 5.95 (d, J= 15.6 Hz, 1H, vinyl), 4.82 (m, 1H, CH-OH), 3.98 (m, 2H, CH-O-C=O + CH-O-Si), 2.03-2.91 (m, 10H), 1.03 (s, 9H, (CH3)3C-). 13C-NMR {400 MHz, CDCl3, δ (ppm)}: 198.4 (C), 176.1 (C), 144.4 (CH), 140.9 (C), 135.8 (CH), 133.1 (C), 132.9 (C), 131.2 (CH), 129.9 (CH), 128.4 (CH), 128.3 (CH), 127.7 (CH), 126.1 (CH), 82.7 (CH), 78.1 (CH), 56.7 (CH), 42.2 (CH2), 41.7 (CH), 40.6 (CH2), 34.5 (CH2), 29.8 (CH2), 26.7 (3x CH3), 18.9 (C). HPLC-MS (ESI): [M+H]+ = 539; [M+H2O]+ = 556; [2M+Na]+ = 1099.

Reference： [1]Current Patent Assignee: ZHEJIANG XIANJU PHARMACEUTICAL COMPANY LIMITED - EP2495235, 2012, A1 Location in patent: Page/Page column 19-20

79
(3R)-3-[(tert-butyl)(dimethyl)silyl]oxy}-5-oxopentyl 2,2-dimethylpropanoate [ No CAS ]
[ 41162-19-0 ]
(3S,5E)-3-[(tert-butyl)(dimethyl)silyl]oxy}-7-oxo-9-phenylnon-5-en-1-yl 2,2-dimethylpropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.28 g	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With barium hydroxide octahydrate In tetrahydrofuran for 0.5h; Inert atmosphere; Stage #2: (3R)-3-[(tert-butyl)(dimethyl)silyl]oxy}-5-oxopentyl 2,2-dimethylpropanoate In tetrahydrofuran; water at 20℃; for 0.5h; Inert atmosphere;

Reference： [1]Nagaiah, Burea; Narsaiah, Akkirala Venkat [Helvetica Chimica Acta, 2013, vol. 96, # 10, p. 1948 - 1954]

80
C₂₂H₁₈O₄ [ No CAS ]
[ 41162-19-0 ]
(-)-katsumadain A [ No CAS ]
(+)-katsumadain A [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80 % ee	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium hexamethylsilazane In tetrahydrofuran at -40℃; for 1h; Inert atmosphere; Stage #2: C₂₂H₁₈O₄ In tetrahydrofuran at -40℃; for 2h; Inert atmosphere; Overall yield = 52 %;	Synthesis of compound (-)-katsumadain A To a solution of 6 [5] (1.0 mmol) in 20 mL dry THF cooled at under N2, was added KHMDS (1.2 mL, 1 M solution in THF). The reaction mixture was stirred 1 h at -40 °C, then added the solution of 5a in 10 mL dry THF and stirred for another 2 h. The reaction was quenched by saturated aqueous NH4Cl, and extracted with EA. The organic layers were collected, washed with brine, dried over by MgSO4, filtered and purified by column chromatography to give katsumadain A (52%) as yellow solid. The ee value of synthetic (-)-1 was determined to be 80%.

Reference： [1]Wang, Yongguang; Bao, Ruiyang; Huang, Shengdian; Tang, Yefeng [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1601 - 1606]

81
C₂₂H₁₈O₄ [ No CAS ]
[ 41162-19-0 ]
katsumadain A [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium hexamethylsilazane In tetrahydrofuran at -40℃; Inert atmosphere; Stage #2: C₂₂H₁₈O₄ In tetrahydrofuran at -40℃; Inert atmosphere;

Reference： [1]Wang, Yongguang; Bao, Ruiyang; Huang, Shengdian; Tang, Yefeng [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1601 - 1606]

82
[ 41162-19-0 ]
(1-diazo-2-oxo-4-phenylbutyl)phosphonic acid dimethyl ester. [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With 4-toluenesulfonyl azide; potassium carbonate

Reference： [1]Seo, Yeon Ji; Kim, Jin-Ah; Lee, Hyeon-Kyu [Journal of Organic Chemistry, 2015, vol. 80, # 17, p. 8887 - 8902]

83
[ 512-56-1 ]
[ 352276-27-8 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
73 g	In acetonitrile at 65℃; for 3h;	Synthesis of dimethyl 2-oxo-4-phenylbutylphosphonate (6) To a degassed stirred solution of 5 (80 g, 1 mmol) in acetone (480 mL), was added sodium iodide(63 g, 1.2 mmol) and stirred at room temperature for 12 h. After completion of the reaction, reaction mixturewas filtered and washed with acetone (200 mL).Then the filtrate was evaporated in vacuo and obtainedcrude product was dissolved in dichloromethane (800mL), washed with water (500 mL) and brine solution(500 mL), dried over anhydrous Na2SO4. The collectedorganic solution was concentrated under reducedpressure to get iodo compound (90 g). To a solution of iodo compound (90 g, 1 mmol) inacetonitrile (450 mL), tri methyl phosphate (77.5 mL, 2mmol) was added at room temperature and stirred for 3h at 65°C. After completion of the reaction as indicatedin TLC, excess of tri methyl phosphate was removedunder high vacuum and obtained crude product purifiedby silica gel chromatography using ethyl acetateand hexane mixture (50:50) to afford compound 6 as abrown liquid (73 g, 86.73%).1H NMR (300 MHz, CDCl3): δ2.9 (q, 4H), 3.0(s, 1H), 3.1 (s, 1H), 3.75 (s, 6H), 7.2 (m, 3H), 7.3(m, 2H). 13C NMR (100 MHz, CDCl3): δ29.35, 40.81,42.08, 45.45, 52.92, 52.98, 126.11, 128.32, 128.41,140.47, 200.80, 200.86.
	In acetonitrile at 65℃; for 3h; Inert atmosphere;	Synthesis of dimethyl 2-oxo-4-phenylbutylphosphonate(7): General procedure: Trimethyl phosphate (87.45 g, 1 mmol) was added tocompound 6 (160 g, 1 mmol) in acetonitrile (320 mL) at roomtemperature and stirred for 3 h at 65 C. The reaction progresswas monitored with TLC. The reaction mixture was dissolvedin sodium bicarbonate solution (1000 mL) and extracted withethyl acetate (2 × 800 mL). The collected organic fractions werewashed with sodium chloride solution and dried over sodiumsulphate. The solvent was removed under vacuum to afford crudeproduct. The crude compound was chromatographed on silica gelusing ethyl acetate and hexane mixture (50:50) to give compound7 as a liquid (72 g). 1 H NMR, 13 C NMR spectra of compound 7matches with the spectral data reported in previous paper [12].

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]
[2]Kamidi, Vijendhar; Kale, Pooja; Boodida, Sathyanarayana [Asian Journal of Chemistry, 2017, vol. 29, # 12, p. 2767 - 2770]

84
[ 41162-19-0 ]
C₂₄H₃₈O₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

85
[ 41162-19-0 ]
C₃₀H₅₂O₄Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C 3.1: triethylamine / dichloromethane / 5 h / 5 - 10 °C

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

86
[ 41162-19-0 ]
C₃₀H₅₄O₄Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C 3.1: triethylamine / dichloromethane / 5 h / 5 - 10 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1 h / -70 °C

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

87
[ 41162-19-0 ]
C₃₅H₆₂O₅Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C 3.1: triethylamine / dichloromethane / 5 h / 5 - 10 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1 h / -70 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 6 h / 5 °C

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

88
[ 41162-19-0 ]
C₃₈H₆₈O₅Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C 3.1: triethylamine / dichloromethane / 5 h / 5 - 10 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1 h / -70 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 6 h / 5 °C 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 16 h / 30 °C

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

89
[ 41162-19-0 ]
C₄₄H₈₂O₅Si₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: lithium hydroxide monohydrate / tert-butyl methyl ether / 1 h / 20 °C 1.2: 0.92 h / 5 °C 2.1: nickel(II) chloride hexahydrate; sodium tetrahydroborate / methanol / 3 h / 0 °C 3.1: triethylamine / dichloromethane / 5 h / 5 - 10 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1 h / -70 °C 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 6 h / 5 °C 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 16 h / 30 °C 7.1: triethylamine / dichloromethane / 6 h / 5 - 10 °C

Reference： [1]Vijendhar; Srinivas; Boodida, Sathyanarayana [Journal of Chemical Sciences, 2015, vol. 127, # 11, p. 2023 - 2028]

90
[ 58503-60-9 ]
[ 41162-19-0 ]
C₁₃H₁₅N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran at -50 - 0℃; Inert atmosphere; Stage #2: 3-azidopropanal In tetrahydrofuran at -10 - 20℃; for 1.83333h; Inert atmosphere;	(E)-7-Azido-1-(4-methoxyphenyl)hept-4-en-3-one S3 General procedure: Sodium hydride (60% dispersion in oil, 1.54g, 38.6mmol) was added portionwise to a solution of 7d (8.50 g, 29.7 mmol) in anhydrous THF (100 mL) at -50°C under argon. The resulting suspension was warmed from -78°C to 0°C over 2.5 h, then cooled to -10°C and a solution of 3-azidopropanal15 (3.82 g, 38.6 mmol) in THF (20 mL) was added over 5 min. The reaction mixture was stirred between 0 and -10°C for 1 h, then at rt for 45 min. Water (50 mL) was then added and extracted with Et2O (2×50 mL). The combined organics were washed with brine (50 mL), dried (Na2SO4) and concentrated to afford a brown oil (10.1 g). The crude product was purified by automated chromatography (2×40 g columns, 0-25% EtOAc in hexanes over 15 min) to afford the title compound

Reference： [1]McLeod, Michael C.; Aubé, Jeffrey [Tetrahedron, 2016, vol. 72, # 26, p. 3766 - 3774]

91
[ 41162-19-0 ]
C₂₅H₄₁NO₆ [ No CAS ]
C₃₅H₅₁NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃; for 0.5h; Inert atmosphere; Stage #2: C₂₅H₄₁NO₆ In acetonitrile at -15 - 20℃; Inert atmosphere;	26.2 Under the nitrogen atmosphere, the 152 mg compound IXa (according to literature Bioorg.Med.Chem.Lett1998, 8, 2849 method for preparing) and lithium chloride (200 mg) of a mixture of acetonitrile (10 ml) cooled to -15 °C. The diisopropyl ethylamine (0.3 ml) are added to a reaction system, in -15 ° C mixture under stirring 30 minutes. Step 1 the compound obtained from VIa acetonitrile (3 ml) solution is added to the reaction system. Reaction system in -15 ° C lower stirring 30 minutes and then gradually returned to room temperature, stirring overnight. The ethyl ether (50 ml) is added to the system, is filtered to remove the solid, the filtrate concentrated under reduced pressure. Residues to column chromatography purification to obtain compound VIIa.

Reference： [1]Current Patent Assignee: UNITRIS BIOPHARMA CO LTD - CN102757459, 2016, B Location in patent: Paragraph 0140; 0142; 0146-0147

92
[ 383-63-1 ]
[ 41162-19-0 ]
[ 100-58-3 ]
(E)-6,6,6-trifluoro-1,5-diphenylhex-4-en-3-one [ No CAS ]
(Z)-6,6,6-trifluoro-1,5-diphenylhex-4-en-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 51% 2: 4%	Stage #1: ethyl trifluoroacetate,; phenylmagnesium bromide In diethyl ether; water at -80 - 0℃; for 2h; Inert atmosphere; Stage #2: dimethyl(2-oxo-4-phenylbutyl)phosphonate With triethylamine; lithium bromide In tetrahydrofuran; diethyl ether; water at 0 - 40℃; for 5.16h; Inert atmosphere;	General method for the preparation of ,-unsaturated ketones General procedure: To a flame-dried two-necked 200 mL flask containing ethyl trifluoroacetate (2.4mL, 20.0 mmol) and 40.0 mL of Et2O was added PhMgBr (prepared in Et2O, 0.95 M,21.0 mL, 20.0 mmol) under an argon atmosphere at 80 °C, then the mixture was stirredfor 1 h at that temperature and another 1 h at 0 °C with the aid of an ice bath where 1.8mL of H2O (100.0 mmol) was added.To a different two-necked flask containing 2.8 g of lithium bromide (32.0 mmol)and THF (60 mL) were added 6.0 g of dimethyl 2-oxo-2-phenylethylphosphonate (26.0mmol) and 3.8 mL of triethylamine (28.0 mmol) at 0 °C under argon atmosphere, andthe whole mixture was stirred for 10 min at room temperature. After cooling to 0 °C,the above solution was introduced to this flask with the aid of cannula, and the resultant mixture was stirred for 5 h at 40 °C. 1 M HCl aq. was added to this mixture whichwas further extracted three times with AcOEt. To the combined AcOEt phase wasadded anhydrous MgSO4 and after filtration, concentration and purification by silica gelchromatography (Hex:AcOEt = 20:1) furnished 4.1 g of the title compound

Reference： [1]Hamada, Yoko; Kawasaki-Takasuka, Tomoko; Yamazaki, Takashi [Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1507 - 1512]

93
[ 512-56-1 ]
[ 31984-10-8 ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
72 g	In acetonitrile; at 65℃; for 3h;Inert atmosphere;	Trimethyl phosphate (87.45 g, 1 mmol) was added tocompound 6 (160 g, 1 mmol) in acetonitrile (320 mL) at roomtemperature and stirred for 3 h at 65 C. The reaction progresswas monitored with TLC. The reaction mixture was dissolvedin sodium bicarbonate solution (1000 mL) and extracted withethyl acetate (2 × 800 mL). The collected organic fractions werewashed with sodium chloride solution and dried over sodiumsulphate. The solvent was removed under vacuum to afford crudeproduct. The crude compound was chromatographed on silica gelusing ethyl acetate and hexane mixture (50:50) to give compound7 as a liquid (72 g). 1 H NMR, 13 C NMR spectra of compound 7matches with the spectral data reported in previous paper [12].

Reference： [1]Asian Journal of Chemistry,2017,vol. 29,p. 2767 - 2770

94
(2-hydroxy-4-phenyl-butyl)-phosphonic acid dimethyl ester [ No CAS ]
[ 41162-19-0 ]

Yield	Reaction Conditions	Operation in experiment
15.8 g	With Jones reagent In acetone for 5h; Cooling with ice;	3 The previous crude product (100 mmol, 1.0 eq. By theoretical) was dissolved in 200 mL of acetone and then an ice-water bath40mL Jones reagent (8N-CrO3: 10.7g dissolved in 8.8mL concentrated sulfuric acid, then add 31.2mL water dilute40mL solution was obtained) (110mmol, 1.1eq.) After the reaction system was stirred for 5h, the reaction was complete detection of raw materials, was added 7mL differentPropanol, stirred for 3 hours, filtered, washed with acetone and the solvent was distilled off under reduced pressure. 60 mL of water was added, extracted with dichloromethane (80 mL *2). The organic phase was then concentrated to give the crude product, which was finally purified by column chromatography to give 15.8 g of product with 98% purity in two stepsThe total yield was 62%

Reference： [1]Current Patent Assignee: NANTONG SHUCHUANG PHARMA; NANTONG TONGTENG PHARMACEUTICAL - CN107011377, 2017, A Location in patent: Paragraph 0093; 0096; 0097

95
[ 41162-19-0 ]
[ 563-96-2 ]
(E)-4-oxo-6-phenylhex-2-enoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at -20℃; for 2h; stereoselective reaction;

Reference： [1]Sivák, Ivan; Toběrný, Michal; Kyselicová, Andrea; Caletková, Ol'Ga; Berkeš, Dušan; Jakubec, Pavol; Kolarovič, Andrej [Journal of Organic Chemistry, 2018, vol. 83, # 24, p. 15541 - 15548]

96
[ 41162-19-0 ]
[ 62961-72-2 ]
(3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: Corey aldehyde In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	1.2; 2.2; 3.2; 4.2; 5.2; 6.2; 7.2; 8.2; 9.2 (2) Synthesis of compound 3 Suspend compound 7 (8.4 g, 33 mmol) in anhydrous THF (200 mL) under nitrogen protection at 0°C,Potassium tert-butoxide (10 g, 90 mmol) was added to the above suspension in batches, and the above suspension was stirred for 30 min at 0°C. A THF (20 mL) solution of compound 2 (3.8 g, 22 mmol) was slowly added dropwise to the above solution.Then, the reaction was transferred to room temperature, and the reaction was stirred for 6 h. After the reaction is complete, add saturated NH4Cl solution (50mL) to quench the reaction, extract with ethyl acetate (100mL×3), combine the organic phases, wash with saturated brine, dry with anhydrous Na2SO4, filter, concentrate, and separate and purify by column chromatography, a light yellow oil 3 (5.9 g, 88%) was obtained.
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: Corey aldehyde In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere;

Reference： [1]Current Patent Assignee: NANJING QIYUN GAOHUO PHARMACEUTICAL TECH - CN111777538, 2020, A Location in patent: Paragraph 0044; 0048-0050; 0060; 0064-0066; 0076; 0080-0082
[2]Zhu, Kejie; Hu, Sha; Liu, Minjie; Peng, Haihui; Chen, Fen-Er [Angewandte Chemie - International Edition, 2019, vol. 58, # 29, p. 9923 - 9927][Angew. Chem., 2019, vol. 131, # 29, p. 10028 - 10032,5]

97
[ 41162-19-0 ]
ethyl 2-((1R,2S,3R)-3-(dimethyl(phenyl)silyl)-2-formyl-5-oxocyclopentyl)acetate [ No CAS ]
ethyl 2-((1R,2R,3R)-3-(dimethyl(phenyl)silyl)-5-oxo-2-((E)-3-oxo-5-phenylpent-1-en-1-yl)cyclopentyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at 20℃; for 6h; Inert atmosphere;

Reference： [1]Hayashi, Yujiro; Umekubo, Nariyoshi [European Journal of Organic Chemistry, 2020, vol. 2020, # 39, p. 6221 - 6227]

98
[ 104-53-0 ]
[ 41162-19-0 ]
[ 79559-59-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; for 0.666667h; Inert atmosphere; Stage #2: 3-phenyl-propionaldehyde In tetrahydrofuran at 40℃; for 12h;	1.c Step c 1-4 (190 mg, 0.75 mmol) Was dissolved THF (5 ml), and potassium carbonate (110 mg, 0.83 mmol), N was added.2After replacement 3 times, the reaction 40 min. The THF solution (3 -) 100 mg phenylpropanal (0.75 mmol, 2 ml) was added, moved to 40 °C under reaction 12h, TLC monitoring reaction was complete and the reaction system was cooled to room temperature. After removing the solvent under reduced pressure, the residue was extracted with ethyl acetate (10 ml), washed with water (10 ml) and saturated aqueous solution of sodium chloride (10 ml) followed by drying over anhydrous sodium sulfate and concentrated to give the product 1 (colorless oily liquid, 182 mg, yield 92%).

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; FUDAN UNIVERSITY; Shanghai Institute of Materia Medica (in: CAS) - CN111792990, 2020, A Location in patent: Paragraph 0070-0071; 0076-0077

99
[ 14371-10-9 ]
[ 41162-19-0 ]
trans,trans-1,7-diphenyl-4,6-heptadien-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: (E)-3-phenylpropenal at 40℃;

Reference： [1]Wang, Congcong; Zhang, Yu-Fang; Guo, Shimeng; Zhao, Quan; Zeng, Yanping; Xie, Zhicheng; Xie, Xin; Lu, Boxun; Hu, Youhong [Journal of Medicinal Chemistry, 2021, vol. 64, # 2, p. 941 - 957]

100
[ 41162-19-0 ]
[ 38754-71-1 ]
[ 41639-73-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / dichloromethane; water 2: D-Glucose; nicotinamide adenine dinucleotide phosphate / aq. phosphate buffer / pH 7 / Enzymatic reaction

Reference： [1]Chen, Fener; Huang, Zedu; Jiang, Meifen; Li, Weijian; Tang, Pei; Ye, Baijun; Zhang, Guo-Tai; Zhu, Kejie [Chemical Science, 2021, vol. 12, # 30, p. 10362 - 10370]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	41162-19-0	MDL No. :	MFCD02093040
Formula :	C₁₂H₁₇O₄P	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ONYIBVIIOCEBIV-UHFFFAOYSA-N
M.W :	256.23	Pubchem ID :	2733973
Synonyms :

Num. heavy atoms :	17
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.42
Num. rotatable bonds :	7
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	66.48
TPSA :	62.41 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.07 cm/s

Log Po/w (iLOGP) :	2.36
Log Po/w (XLOGP3) :	1.12
Log Po/w (WLOGP) :	2.67
Log Po/w (MLOGP) :	1.45
Log Po/w (SILICOS-IT) :	1.9
Consensus Log Po/w :	1.9

[ CAS No. 41162-19-0 ] {[proInfo.proName]}

Quality Control of [ 41162-19-0 ]

Related Doc. of [ 41162-19-0 ]

Product Details of [ 41162-19-0 ]

Calculated chemistry of [ 41162-19-0 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 41162-19-0 ]

Application In Synthesis of [ 41162-19-0 ]

[ 41162-19-0 ] Synthesis Path-Downstream 1~100

Technical Information

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-1.93
Solubility :	2.99 mg/ml ; 0.0117 mol/l
Class :	Very soluble
Log S (Ali) :	-2.02
Solubility :	2.42 mg/ml ; 0.00946 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.84
Solubility :	0.0372 mg/ml ; 0.000145 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	3.1

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
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