* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] European Journal of Organic Chemistry, 1999, # 11, p. 2909 - 2914
2
[ 50-00-0 ]
[ 1779-58-4 ]
[ 15484-46-5 ]
Yield
Reaction Conditions
Operation in experiment
85%
With potassium carbonate In water at 10 - 20℃; for 6 h;
Three bottle adding 119.2 g methoxy carbonyl methylene triphenyl bromination phosphorus, 300 ml water and 58 g 30percent formaldehyde aqueous solution, control 10 - 15 °C slowly dropping 30percent potassium carbonate aqueous solution to 266.8 g, then completing 15 - 20 °C lower heat insulating 6 hours, filtering to remove the insoluble matter (triphenyl phosphate). The filtrate by adding dichloromethane 500 ml extraction, the organic phase is concentrated, after removing the solvent control 70 - 90 °C, vacuum degree 0.098 mpa under reduced pressure distillation, to obtain 2 - hydroxy methyl methacrylate 25.7 g (yield 85percent).
Reference：
[1] Patent: CN106336357, 2017, A, . Location in patent: Paragraph 0031; 0034; 0035
General procedure: To a stirred solution of PPh3 (1.7 g, 6.7 mmol) in ethylacetate, a solution of methyl 2-bromoacetate (0.62 μL,6.5 mmol) in ethyl acetate was added at room temperature.After 17 h, a white precipitate was collectedby filtration, washed three times with ether and driedin air to furnish (2-methoxy-2-oxoethyl)triphenylphosphoniumbromide (4, 2.49 g) as a white solid in almostquantitative yield. The phosphonium bromide 4 (2.0 g,4.81 mmol) was added to a suspension of sodium ethoxide(340 mg) in ethanol (10 mL) followed by the additionof 3a (1.15 g, 4.75 mmol) at room temperature for 25 min.The mixture was stirred at 50–55°C for 1 h. The progressof the reaction was monitored via TLC. After completionof the reaction, water (10 mL) was added to the reactionmixture, and the product was extracted four timeswith diethyl ether (20 mL). The organic layers were combined,dried over anhydrous sodium sulfate and evaporatedunder reduced pressure to furnish a solid residue.Further purification by column chromatography (ethylacetate : hexane 3 : 7) afforded two methyl cinnamatederivatives as a 3.5 : 1 mixture of E- and Z-isomers,respectively.
92%
Reflux
(1) Synthesis of phosphorus salt To a 50mL round bottom flask containing 10 mL of water and toluene was added triphenylphosphine (1.31g, 5.0mmol) and methyl bromoacetate(0.76g, 5.0mmol), afterwhich it was installed with a condenser connected to adrying tube, then refluxed overnight. The reaction system was cooled, the toluene was removed by filtration, to obtain a white solid phosphonium salt,and dried in vacuo to obtain the product (1.9 g of, 92percent yield).
90%
With potassium iodide; sodium hydroxide In water; toluene at 65 - 75℃; for 20 h; Inert atmosphere
(0.09 mol) of KI in 200 ml of water was added to toluene and 44.4 g (0.29 mol) of 2-bromoacetic acid (0.29 mol) was added to a solution of 888 (0.29111001) triphenylphosphine, Methyl ester. Nitrogen protection down to 65 ~ 75 ° C, insulation 20h. After the end of the insulation, cool to 50 ~ 60 ° C, add 350ml of water, phase separation. The water was incubated at 40 ° C and slowly added 268.4 g of 10percent sodium hydroxide solution. After incubation for 30 min, the filter was filtered and the filter cake was rinsed with 40 ml of n-heptane and dried at 50 ° C under reduced pressure to give a yellow solid. G, the yield of 90percent.
89%
at 20℃; for 3 h;
To a solution of triphenylphosphine (942 mg, 3.6 mmol) in dry THF (3 mL) was added methyl 2-bromoacetate (500 mg, 3.27 mmol) and the mixture was stirred at rt for 3h. The product was filtered, washed with THF and dried under reduced pressure to give a colourless solid 57 (1.20 g, 89percent). HPLC: 4.91 min (99percent).
Reference：
[1] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2017, vol. 72, # 2, p. 119 - 124
[2] European Journal of Organic Chemistry, 2002, # 13, p. 2094 - 2108
[3] Phosphorus, Sulfur and Silicon and the Related Elements, 2008, vol. 183, # 5, p. 1188 - 1208
[4] Helvetica Chimica Acta, 2003, vol. 86, # 2, p. 310 - 323
[5] Heterocycles, 2007, vol. 73, # C, p. 751 - 768
[6] Journal of Organic Chemistry, 2014, vol. 79, # 5, p. 2105 - 2110
[7] Patent: CN103965066, 2016, B, . Location in patent: Paragraph 0108; 0109; 0110
[8] Patent: CN106336357, 2017, A, . Location in patent: Paragraph 0031-0033
[9] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 4903 - 4909
[10] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 12, p. 1569 - 1572
[11] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 7, p. 2768 - 2781
[12] Helvetica Chimica Acta, 1957, vol. 40, p. 1242,1246
[13] Chemische Berichte, 1961, vol. 94, p. 578 - 584
[14] Australian Journal of Chemistry, 1997, vol. 50, # 12, p. 1129 - 1135
[15] European Journal of Organic Chemistry, 1999, # 11, p. 2909 - 2914
[16] Patent: US4464391, 1984, A,
[17] Patent: US4024163, 1977, A,
[18] Organic Letters, 2008, vol. 10, # 3, p. 429 - 432
[19] Patent: US2005/203162, 2005, A1, . Location in patent: Page/Page column 19
[20] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 5, p. 1988 - 2000
[21] Patent: EP2287157, 2011, A1, . Location in patent: Page/Page column 15-16
[22] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 23, p. 7262 - 7269
[23] European Journal of Organic Chemistry, 2012, # 12, p. 2323 - 2330
[24] Chemical Communications, 2013, vol. 49, # 33, p. 3470 - 3472
[25] European Journal of Organic Chemistry, 2013, # 36, p. 8214 - 8244
[26] Journal of Organic Chemistry, 2014, vol. 79, # 3, p. 1386 - 1398
[27] Organic Letters, 2014, vol. 16, # 11, p. 2990 - 2992
[28] RSC Advances, 2014, vol. 4, # 40, p. 21134 - 21140
[29] Organic Letters, 2014, vol. 16, # 13, p. 3440 - 3443
5
[ 1685-97-8 ]
[ 21204-67-1 ]
[ 1779-58-4 ]
[ 134898-37-6 ]
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 1991, vol. 60, # 1.2, p. 49 - 55
6
[ 134898-34-3 ]
[ 21204-67-1 ]
[ 1779-58-4 ]
[ 134898-37-6 ]
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 1991, vol. 60, # 1.2, p. 49 - 55
7
[ 16619-55-9 ]
[ 21204-67-1 ]
[ 1779-58-4 ]
[ 134898-28-5 ]
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 1991, vol. 60, # 1.2, p. 49 - 55
8
[ 134898-25-2 ]
[ 21204-67-1 ]
[ 1779-58-4 ]
[ 134898-28-5 ]
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 1991, vol. 60, # 1.2, p. 49 - 55
With lithium hexamethyldisilazane; In tetrahydrofuran;
Part A. Preparation of 4-[4-(2-methoxycarbonyl-vinyl)-piperidine-1-sulfonyl]-tetrahydro-pyran-4-carboxylic Acid tert-butyl Ester A 100 mL round-bottom flask was charged with (carbomethoxymethyl)triphenylphosphonium bromide (5.99 g, 14.4 mmol) and tetrahydrofuran (30 mL). This resulted in a white slurry. The flask was then immersed into an ice bath, and a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (15 mL, 15 mmol) was added dropwise while maintaining the temperature at less than 5° C. After complete addition, the reaction mixture was stirred with cooling for 15 min. A solution of the aldehyde from Example A4 (4.0 g, 11.1 mmol) in tetrahydrofuran (10 mL) was then added dropwise, maintaining the temperature at less than 5° C. After complete addition, the flask was slowly warmed to room temperature and then stirred for 1 hr. The resulting mixture was diluted with diethyl ether (150 mL), resulting in a white precipitate. The solid was filtered, and the filtrate was washed with water 1*100 mL), 5percent HCl solution (2*100 mL), and brine (1*100 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography (25-40percent ethyl acetate/hexane) afforded 2.09 g of a colorless crystalline solid product (45percent yield). 1H NMR (CDCl3) predominantly one geometric isomer (>95percent): delta 1.53 (s, 9H), 1.76 (d, J=13.5 Hz, 2H), 2.10 (td, J=4.7, 12.6 Hz, 2H), 2.32 (d, J=12.6 Hz, 2H), 3.00 (t, J=12.4 Hz, 2H), 3.31 (t, J=12 Hz, 2H), 3.79 (s, 3H), 3.81 (d, J=12.3 Hz, 2H), 3.97 (dd, J=4.1, 11.9 Hz, 2H), 5.81 (d, J=15.9 Hz, 1H), 6.89 (dd, J=6.6, 15.9 Hz, 1H); Electrospray mass spectrometry showed m/z=418 (M+H).
45%
A 100 mL round-bottom flask was charged with (carbomethoxymethyl)triphenylphosphonium bromide (5.99 g, 14.4 mmol) and tetrahydrofuran (30 mL). This resulted in a white slurry. The flask was then immersed into an ice bath, and a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (15 mL, 15 mmol) was added dropwise while maintaining the temperature at less than 5° C. After complete addition, the reaction mixture was stirred with cooling for 15 min. A solution of the aldehyde from Example A4 (4.0 g, 11.1 mmol) in tetrahydrofuran (10 mL) was then added dropwise, maintaining the temperature at less than 5° C. After complete addition, the flask was slowly warmed to room temperature and then stirred for 1 hr. The resulting mixture was diluted with diethyl ether (150 mL), resulting in a white precipitate. The solid was filtered, and the filtrate was washed with water (1?100 mL), 5percent HCl solution (2?100 mL), and brine (1?100 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography (25-40percent ethyl acetate/hexane) afforded 2.09 g of a colorless crystalline solid product (45percent yield). 1H NMR (CDCl3) predominantly one geometric isomer (>95percent): ? 1.53 (s, 9H), 1.76 (d, J=13.5 Hz, 2H), 2.10 (td, J=4.7, 12.6 Hz, 2H), 2.32 (d, J=12.6 Hz, 2H), 3.00 (t, J=12.4 Hz, 2H), 3.31 (t, J=12 Hz, 2H), 3.79 (s, 3H), 3.81 (d, J=12.3 Hz, 2H), 3.97 (dd, J=4.1, 11.9 Hz, 2H), 5.81 (d, J=15.9 Hz, 1H), 6.89 (dd, J=6.6, 15.9 Hz, 1H), Electrospray mass spectrometry showed m/z=418 (M+H).
With sodium hydride; In tetrahydrofuran;Heating / reflux;
Carbomethoxy triphenylphosphonium bromide (45 g) was added to a solution of tetrahydropyran-4-one (10 g) in THF (100 ml). Sodium hydride (4.2 g) was added carefully in small portions. The suspension was stirred at reflux for 18 h, then cooled, filtered and evaporated. The residue was filtered through silica, eluting with Et2O/hexane 1: 1 to give the title compound as a colourless oil (13 g). MS 156 (M)
(R)-2[(2,5,7,8-Tetramethyl-2-(3 Propene Methyl Ester)chroman-6-yloxy]acetic Acid (28) To a slurry of (carbomethoxymethyl)triphenyl phosphonium bromide (1.8 gm, 4.32 mmol) in 12 ml of THF at ° C. was added 1.66 ml of n-BuLi (2.5M in hexane) dropwise. The resulting solution was removed to room temperature for 2 h, and then a solution of (+)S-6-[dimethyl(1,1-dimethylethyl)silyl]-2,5,7,8-tetramethyl chroman-2-carbaldhyde (1.31 g, 3.76 mmol) in 7 ml THF was added via cannula. The solution was stirred at room temperature for 44 hr and then 10 ml of 1N aq. HCl was added. The layer were separated and then aq. phase was extracted with ether (3*15 ml). The combined organic layer were washed with brine, dried over Na2SO4 and filtered. After concentration of the filtrate, the crude alkene was purified by flash chromatography eluding with dichloromethane to give mixture of the cis and trans alkene in 93percent yield. The silyl ether mixture of cis and trans alkene (3.76 mmol) was dissolved in THF and tetra-n-butylammoniumfluoride (0.041 mole) was added. After being stirred at 23° C. for 1.5 h, the mixture was poured into water and extracted into ether. The ether extract was dried concentrated and purified by silica gel chromatography eluding with EtOAc in hexane (3:7) and both the cis and trans isomer of 2,5,7,8-tetramethyl-2R-(3'propenemethyl ester)-6-chromanol were isolated and characterized (68percent yield) 1H-NMR (CDCl3/TMS, ppm): 1.65 (s, 3H, 2a CH3), 2.12 (m, 2H, 3CH2), 2.39 (s, 9H, CH3), 2.48 (m, 2H, 4CH2), 3.78 (s, 3H, OCH3), 6.11 (d, 1H, CH=) and 7.13 (d, 1H, CH=).
To a suspension of (2-methoxy-2-oxo-ethyl)-triphenyl-phosphonium bromide (1.502 g, 3.618 mmol) in THF (15 mL) under nitrogen at room temperature was added LHMDS in THF (3.358 mL of 1 M, 3.358 mmol) dropwise. The mixture was stirred for 10 mins then cooled to -25 0C. l-(3-bromo-5-formyl-phenyl)cyclopropane-l- carbonitrile (500 mg, 1.999 mmol) was dissolved in 1 mL of THF and added to the <n="161"/>reaction. The reaction was allowed to warm to room temperature over 1 hour. The reaction was quenched with MeOH (2 mL) and then partitioned between ethyl acetate and brine. The aqueous was extracted with ethyl acetate and dried, filtered and concentrated. The crude product was purified on silica (Companion, 24 g) eluting with 1-20percent EtOAc:Petrol ether to give methyl (E)-3-[3-bromo-5-(l-cyanocyclopropyl)phenyl]prop-2-enoate as a yellow solid (594 mg, 97percent).
Methyl 4-azido-5,7-0-benzvlidene-6-0-teff-butyldimethvlsilvl-2,3.4-trideoxv-D-gu/o-oct-2-enoate 2.5; 2-Azido-3,5-0-benzylidene-6-0-terf-butyldimethylsilyl-2-deoxy-D-gulonolactone 2.4 (3.96 g, 9.77 mmol) was dissolved in DCM (50 ml). This solution was cooled to 0 °C after which a 1.5M solution of DiBAL-H in toluene(9.77 ml) was added. The resulting mixture was stirred at 0 °C for 45 minutes. After addition of 1M HCI (50 ml), the layers were separated and the organic fraction was dried on Na2S04 and the solvents were evaporated. (Methoxycarbonylmethyl)triphenylphosphonium bromide (4.87 g, 11.72 mmol) was dissolved in DCM (50 ml) and shaken gently with 2M NaOH (50 ml) for five minutes. The organic layer was dried on Na2S04 and the solvent was evaporated. The ylid was then dissolved in dioxane (50 ml) and added to the crude lactol. The resulting mixture was stirred overnight at room temperature. After evaporation of the solvent and column chromatography (EtOAc/cyclohexane, 1/4 v/v), the product (3.63 g, 80percent) was obtained as a clear, colourless oil.Rf (EtOAc/cyclohexane, 1/2 v/v) 0.72; [a]D -17.0 (c 0.91, CHCI3); v 3445 (OH), 2109 (N3), 1727 (CO); 8H (400 MHz, CDCI3) 0.11, 0.12 (6H, 2 x s, SiCW3)2), 0.93 (9H, s, SiC(CH3)3), 2.75 (1H, d, OH, Jqh.b 10.0 Hz), 3.71 (1H, app. t, H-5, J 9.0 Hz), 3.78 (3H, s, OCH3), 3.88-3.96 (4H, m, H-6, H-7, H-8a, H-8b), 4.52 (1H, dd, H-4, J4,3 6.2 Hz, J4p5 8.8 Hz), 5.58 (1H, s, Ar-CH), 6.20 (1H, d, H-2, J2,3 15.8 Hz), 7.03 (1H, dd, H-3, J3,2 15.8 Hz, J3,4 6.2 Hz), 7.37 (3H, m, ArH), 7.46 (2H, m, ArH); Dc (100 MHz, CDCI3) -5.4, -5.4 (Si(CH3)2), 18.3 (SiC(CH3)3), 25.9 (SiC(CH3)3), 51.8 (OCH3), 60.8 (C-4), 62.5 (C-8), 63.0, 79.8 (C-6, C-7), 81.1 (C-5), 101.1 (Ar-CH), 124.1 (C-2), 125.9, 128.2, 129.1, 137.0 (ArC), 142.6 (C-3), 166.1 (C=0).
2-azido-3,5-O-benzylidene-6-O-tert-butyldimethylsilyl-2-deoxy-L-gulose[ No CAS ]
[ 1779-58-4 ]
[ 874350-69-3 ]
Yield
Reaction Conditions
Operation in experiment
78%
Methyl 4-azido-5.7-0-benzvlidene-8-teff-butvldimethvlsilvl-2,3,4-trideoxv-D-gu/o-oct-2-enoate 1.6; 2-Azido-3,5-0-benzylidene-6-0-ferf-butyldimethylsilyl-2-deoxy-L-gulono-x-lactone 1.4 (3.83 g, 9.44 mmol) was dissolved in DCM (100 ml) and cooled to 0°C. After dropwise addition of a 1.5M solution of DiBAL-H in toluene (9.44 ml), the mixture was stirred at 0°C for three hours, after which IR clearly showed the disappearance of the C=0 absorption of the starting material at 1785 cm"1. Cautiously, 0.5M HCI (100 ml) was added and the layerswere separated, after which the organic fraction was dried on Na2S04. After filtration and evaporation of the solvent, 2-Azido-3,5-0-benzylidene-6-0-fert-butyldimethylsilyl-2-deoxy-L-gulose 1.5 was obtained which was used without purification. (Methoxycarbonylmethyl)triphenylphosphonium bromide (4.30 g, 10.38 mmol) was dissolved in DCM (50 ml) and shaken gently with 2M NaOH (50 ml) for 5 minutes. The layers were separated and the organic layer was dried on Na2S04. After filtration and evaporation of the solvent, the crude phosphorous ylid was redissolved in dioxan (100 ml) and added to crude 2-Azido-3,5-0-benzylidene-6-0-fert-butyldimethylsilyl-2-deoxy-L-gulose 5. The resulting solution was stirred overnight at room temperature. After evaporation of the solvent, the crude material was triturated with pet. ether 40-60. After filtration, the filtrate was evaporated to dryness, and column chromatography (EtOAc/cyclohexane, 1/4 v/v) afforded the product (3.43 g, 78percent) as a clear, colourless oil.Rf (EtOAc/cyclohexane, 1/2 v/v) = 0.67; [a]D +12.8 (c 0.20 g/100 ml, CHCI3); v 3443 (OH), 2109 (N3), 1728 (C=0); SH (400 MHz, CDCI3) 0.10, 0.11 (6H, 2 x s, SiCH3), 0.92 (9H, s, SiC(CH3)3), 2.74 (1H, OH, Joh.b 9.6 Hz), 3.71 (1H, dd, H-5, J5,4 1.0 Hz, J5,6 5.4 Hz), 3.77 (3H, s, OCH3), 3.93 (4H, m, H-6, H-7, H-8a, H-8b), 4.53 (1H, m, H-4), 5.58 (1H, s, ArCH), 6.20 (1H, dd, H-2, J2]4 14 Hz, J2,3 11.8 Hz), 7.03 (1H, dd, H-3, J3|4 6.0 Hz, J3|2 11.8 Hz), 7.46 (5H, m, ArH); 5C (100 MHz, CDCI3) -5.4, -5.4 (SiCH3), 25.9 (SiC(CH3)s), 26.9 (SiC(CH3)3), 51.6 (OCH3), 52.3 (C-5), 60.7 (C-4), 62.9 (C-8), 79.8, 81.0 (C-6, C-7), 101.1 (ArCH), 124.0 (C-2), 125.9, 128.2, 129.1, 133.4 (ArC), 142.6 (C-3), 166.4 (C=0); HRMS m/z (ESI +ve) observed 486.2033 [M+Na+], C22H33N306SiNa requires 486.2036.
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