Home Cart 0 Sign in  
X

[ CAS No. 17145-91-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 17145-91-4
Chemical Structure| 17145-91-4
Chemical Structure| 17145-91-4
Structure of 17145-91-4 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

Quality Control of [ 17145-91-4 ]

Related Doc. of [ 17145-91-4 ]

Alternatived Products of [ 17145-91-4 ]
Product Citations

Product Details of [ 17145-91-4 ]

CAS No. :17145-91-4 MDL No. :MFCD00041347
Formula : C10H21O5P Boiling Point : -
Linear Structure Formula :(CH3CH2O)2POCHCH2CH3CO2CH2CH3 InChI Key :GYUCVQSNZFRDRL-UHFFFAOYSA-N
M.W : 252.24 Pubchem ID :229053
Synonyms :

Safety of [ 17145-91-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 17145-91-4 ]

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

  • Downstream synthetic route of [ 17145-91-4 ]

[ 17145-91-4 ] Synthesis Path-Downstream   1~101

  • 1
  • [ 74-96-4 ]
  • [ 867-13-0 ]
  • [ 17145-91-4 ]
YieldReaction ConditionsOperation in experiment
80% With sodium hydride In 1,2-dimethoxyethane at 0 - 60℃; for 5h;
With sodium hydride 1) DMF, r.t., 1h, 2) 55 deg C, overnight; Yield given. Multistep reaction;
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In 1,2-dimethoxyethane at 20℃; for 1h; Stage #2: ethyl bromide In 1,2-dimethoxyethane for 3h; Heating;
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In 1,2-dimethoxyethane at 20℃; for 2h; Stage #2: ethyl bromide In 1,2-dimethoxyethane at 60℃; for 2h; 4.3.1. General procedure for the synthesis of phosphonates a-e General procedure: Ethyl 2-(diethoxyphosphoryl)acetate (1 eq) was added dropwise to a cooled suspension of NaH (1.1 eq) in dry DME (2 mL/mmol). After stirring at room temperature for 2 h the appropriate halide (1.1 eq) was added, and the mixture was stirred at 60 °C for additional 2 h. After quenching with ice-water, the mixture was extracted with ethyl acetate, and the combined organic layers were washed with H2O and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified through flash chromatography eluting dichloromethane-diethyl ether 95:5 to give the title compounds as colourless oils in yields ranging from 36% to 53%. Analytical data for compounds a-e matched the data published.
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In 1,2-dimethoxyethane at 25℃; for 2h; Stage #2: ethyl bromide In 1,2-dimethoxyethane at 60℃; for 2h;

  • 2
  • [ 17145-91-4 ]
  • [ 116993-95-4 ]
  • [ 130980-99-3 ]
YieldReaction ConditionsOperation in experiment
88% With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In tetrahydrofuran Ambient temperature;
  • 3
  • [ 17145-91-4 ]
  • [ 100-52-7 ]
  • [ 54110-97-3 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: triethyl 2-ethylphosphonoacetate With lithium tert-butoxide In hexane at 25℃; for 0.25h; Stage #2: benzaldehyde In hexane at 25℃; for 4h;
  • 4
  • [ 17145-91-4 ]
  • [ 123-72-8 ]
  • [ 28897-60-1 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: triethyl 2-ethylphosphonoacetate With lithium tert-butoxide In hexane at 25℃; for 0.25h; Stage #2: butyraldehyde In hexane at 25℃; for 4h;
  • 5
  • [ 17145-91-4 ]
  • [ 623-36-9 ]
  • ethyl (4E)-2-ethyl-4-methyl-2,4-heptadienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% Stage #1: triethyl 2-ethylphosphonoacetate With lithium tert-butoxide In hexane at 25℃; for 0.25h; Stage #2: (E)-2-methylpent-2-enal In hexane at 25℃; for 4h;
  • 6
  • [ 17145-91-4 ]
  • 3-(2-methyl-3-oxo-bicyclo[2.2.1]heptan-2-yl)propanal [ No CAS ]
  • (Z)-5-(3-oxo-2-methyl-bicyclo[2.2.1]hept-2-yl)-2-ethyl-2-pentenoic acid ethyl ester [ No CAS ]
  • (E)-5-(3-oxo-2-methyl-bicyclo[2.2.1]hept-2-yl)-2-ethyl-2-pentenoic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 40.2% 2: 26.5% With potassium hexamethylsilazane In tetrahydrofuran; toluene at -80℃;
  • 7
  • [ 17145-91-4 ]
  • [ 311770-86-2 ]
  • [ 311770-43-1 ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran for 1h; Stage #2: benzyl 5-formyl-2-methoxybenzoate In tetrahydrofuran at 20℃; for 4.5h;
74% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran for 1h; Stage #2: benzyl 5-formyl-2-methoxybenzoate In tetrahydrofuran at 20℃; for 4.5h;
With sodium hydride In tetrahydrofuran
  • 8
  • [ 17145-91-4 ]
  • [ 74181-34-3 ]
  • [ 496947-02-5 ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 20℃; Stage #2: 2,2,-dimethyl-1,3-dioxan-5-one In tetrahydrofuran for 1h; Heating;
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran for 0.5h; Reflux; Stage #2: 2,2,-dimethyl-1,3-dioxan-5-one In tetrahydrofuran for 1h; Reflux;
  • 9
  • [ 867-13-0 ]
  • [ 75-03-6 ]
  • [ 17145-91-4 ]
YieldReaction ConditionsOperation in experiment
95.55% Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 0℃; for 0.5h; Stage #2: ethyl iodide In dimethyl sulfoxide at 60℃; for 1.5h;
88% With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 50℃; for 0.833333h;
73% Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 0 - 23℃; Inert atmosphere; Stage #2: ethyl iodide In dimethyl sulfoxide at 50℃; for 0.833333h; Inert atmosphere;
70% With caesium carbonate at 120℃; for 2h; Microwave irradiation;
65% Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In 1,2-dimethoxyethane at 25℃; for 2h; Stage #2: ethyl iodide In 1,2-dimethoxyethane at 60℃; for 2h;
With potassium <i>tert</i>-butylate In dimethyl sulfoxide
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In neat (no solvent) at 120℃; for 2h; Microwave irradiation;

  • 10
  • [ 17145-91-4 ]
  • [ 123-11-5 ]
  • [ 53618-36-3 ]
YieldReaction ConditionsOperation in experiment
99% Stage #1: triethyl 2-ethylphosphonoacetate With potassium <i>tert</i>-butylate In tetrahydrofuran cooling; Stage #2: 4-methoxy-benzaldehyde In tetrahydrofuran at 20℃; for 6h; Further stages.;
74% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil for 1h; Inert atmosphere; Cooling with ice; Stage #2: 4-methoxy-benzaldehyde In tetrahydrofuran; mineral oil at 0 - 20℃; for 4h; Inert atmosphere; 6.1.1. Ethyl 2-(4-methoxybenzylidene)butanoate (5) Sodium hydride (214 mg, 5.35 mmol; 60% oil dispersion) was suspended in 10 mL of dehydrated tetrahydrofuran under argon and cooled with ice. Triethyl 2-phosphonobutyrate (1.34 g, 5.31 mmol) dissolved in 20 mL of dehydrated tetrahydrofuran was added dropwise. When the addition was completed, the mixture was stirred for 1 h, then 4-methoxybenzaldehyde (1.44 g, 5.33 mmol) dissolved in 25 mL of dehydrated tetrahydrofuran was added dropwise, and the mixture was stirred for a further 4 h at room temperature. The reaction mixture was poured into ice/water. The whole was extracted with ethyl acetate, and the organic phase was washed with water and brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluant, n-hexane/ethyl acetate = 5:1 v/v) to afford 1.45 g (74%) of the title compound as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.59 (s, 1H), 7.36 (d, J = 8.5 Hz, 2H), 6.92 (d, J = 8.5 Hz, 2H), 4.26 (q, J = 7.3 Hz, 2H), 3.83 (s, 3H), 2.57 (q, J = 7.3 Hz, 2H), 1.34 (t, J = 7.3 Hz, 3H), 1.18 (t, J = 7.3 Hz, 3H); MS (FAB) 235 (M+H)+.
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran for 1h; Stage #2: 4-methoxy-benzaldehyde In tetrahydrofuran at 0 - 20℃; for 4h;
With potassium <i>tert</i>-butylate In tetrahydrofuran

  • 11
  • [ 17145-91-4 ]
  • [ 31680-08-7 ]
  • [ 334015-21-3 ]
  • 12
  • [ 17145-91-4 ]
  • [ 128843-58-3 ]
  • 2-[1-(4-Benzoyl-1-methyl-1H-pyrrol-2-yl)-meth-(E)-ylidene]-butyric acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With potassium carbonate In ethanol at 70℃; for 2h;
  • 13
  • [ 17145-91-4 ]
  • [ 501125-34-4 ]
  • 2-[1-(1-Methyl-4-phenylacetyl-1H-pyrrol-2-yl)-meth-(E)-ylidene]-butyric acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With potassium carbonate In ethanol at 70℃; for 2h;
  • 14
  • [ 17145-91-4 ]
  • [ 501125-35-5 ]
  • ethyl-3-[4-(3-phenyl-2-propenoyl)-1-methyl-1H-pyrrole-2-yl]-2-ethyl-2-propenoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With potassium carbonate In ethanol at 70℃; for 2h;
  • 15
  • [ 17145-91-4 ]
  • [ 5736-88-9 ]
  • CH3(CH2)3OC6H4C2HCH2CH3CO2CH2CH3 [ No CAS ]
  • 16
  • [ 17145-91-4 ]
  • [ 311770-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran 2: H2 / Pd/C / ethanol
Multi-step reaction with 2 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran 2: H2 / 10 percent Pd/C / ethanol
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr

  • 17
  • [ 17145-91-4 ]
  • [ 311770-49-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: 7.20 g / CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1: NaH / tetrahydrofuran 2: H2 / 10 percent Pd/C / ethanol 3: ClCO2Et; NEt3 / tetrahydrofuran
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine / dichloromethane / 0.17 h / -15 - -10 °C 3.2: -10 - 20 °C
  • 18
  • [ 17145-91-4 ]
  • [ 378232-17-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: tetrahydrofuran / 4 h / 0 - 20 °C 2.1: H2 / Pd/C / tetrahydrofuran; ethanol / 2192.43 Torr
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / Inert atmosphere; Cooling with ice 1.2: 4 h / 0 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 3 h / 2647.76 Torr
  • 19
  • [ 17145-91-4 ]
  • [ 378232-23-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: tetrahydrofuran / 4 h / 0 - 20 °C 2.1: H2 / Pd/C / tetrahydrofuran; ethanol / 2192.43 Torr 3.1: TiCl4 / CH2Cl2 / 6 h / -20 °C 3.2: 97 percent / aq. HCl / CH2Cl2
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / Inert atmosphere; Cooling with ice 1.2: 4 h / 0 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 3 h / 2647.76 Torr 3.1: titanium tetrachloride / dichloromethane / 6 h / -20 °C / Inert atmosphere
  • 20
  • [ 17145-91-4 ]
  • [ 378232-24-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: tetrahydrofuran / 4 h / 0 - 20 °C 2.1: H2 / Pd/C / tetrahydrofuran; ethanol / 2192.43 Torr 3.1: TiCl4 / CH2Cl2 / 6 h / -20 °C 3.2: 97 percent / aq. HCl / CH2Cl2 4.1: 89 percent / NH2OH*HCl; pyridine / ethanol / 6 h / Heating
Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 1 h / Inert atmosphere; Cooling with ice 1.2: 4 h / 0 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 3 h / 2647.76 Torr 3.1: titanium tetrachloride / dichloromethane / 6 h / -20 °C / Inert atmosphere 4.1: pyridine; hydroxylamine hydrochloride / ethanol / 5 h / Reflux
  • 21
  • [ 17145-91-4 ]
  • [ 311771-79-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 22
  • [ 17145-91-4 ]
  • [ 311771-80-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 23
  • [ 17145-91-4 ]
  • [ 311771-78-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 24
  • [ 17145-91-4 ]
  • [ 311771-18-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 25
  • [ 17145-91-4 ]
  • [ 311770-52-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 26
  • [ 17145-91-4 ]
  • [ 311771-76-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 27
  • [ 17145-91-4 ]
  • [ 311770-54-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 28
  • [ 17145-91-4 ]
  • [ 311771-19-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 29
  • [ 17145-91-4 ]
  • [ 311771-77-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 30
  • [ 17145-91-4 ]
  • [ 311770-53-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h 1.2: 74 percent / tetrahydrofuran / 4.5 h / 20 °C 2.1: 98 percent / H2 / Pd/C / ethanol / 3 h / 2647.71 Torr 3.1: Et3N / CH2Cl2 / 0.17 h / -10 °C 4.1: CH2Cl2 / -10 - 20 °C
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h 1.2: 4.5 h / 20 °C 2.1: hydrogen / 10% palladium on activated carbon / ethanol / 3 h / 2647.76 Torr 3.1: chloroformic acid ethyl ester; triethylamine
  • 31
  • [ 17145-91-4 ]
  • Ethyl 2-ethyl-3-(4-methoxyphenyl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
4.58 g (98%) With hydrogenchloride; potassium <i>tert</i>-butylate In tetrahydrofuran Ethyl 2-ethyl-3-(4-methoxyphenyl)acrylate Ethyl 2-ethyl-3-(4-methoxyphenyl)acrylate Under an argon atmosphere, stirring and cooling with ice, a solution of triethyl 2-phosphonobutyrate (5.55 g, 22.0 mmol) in anhydrous tetrahydrofuran (5 mL) was added dropwise to a solution of potassium tert-butoxide (2.47 g, 22.0 mmol) in anhydrous tetrahydrofuran (30 mL), and then the mixture was stirred for 20 minutes. Next, after a solution of p-anisadehyde (2.72 g, 20.0 mmol) in anhydrous tetrahydrofuran (5 mL) was added, the mixture was stirred for 1 hour under cooling with ice and for 4 hours at room temperature. Cooled 0.5 mol/L hydrochloric acid (100 mL) was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent n-hexane:ethyl acetate=15:1 v/v) to afford 4.58 g (98%) of the title compound as a colorless oily product. Mass analysis m/z 234 (M+).
  • 32
  • [ 17145-91-4 ]
  • [ 378232-32-7 ]
  • Ethyl 2-ethyl-3-[4-methoxy-3-[2-[4-(trifluoromethyl)phenyl]ethoxy]phenyl]acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
842 mg (99%) With hydrogenchloride; potassium <i>tert</i>-butylate In tetrahydrofuran Ethyl 2-ethyl-3-[4-methoxy-3-[2-[4-(trifluoromethyl)phenyl]ethoxy]phenyl]acrylate Ethyl 2-ethyl-3-[4-methoxy-3-[2-[4-(trifluoromethyl)phenyl]ethoxy]phenyl]acrylate Under an argon atmosphere, stirring and cooling with ice, a solution of triethyl 2-phosphonobutyrate (555 mg, 2.20 mmol) in anhydrous tetrahydrofuran (5 mL) was added dropwise to a solution of potassium tert-butoxide (250 mg, 2.23 mmol) in anhydrous tetrahydrofuran (10 mL), and then the mixture was stirred for 20 minutes. Following this, a solution of 4-methoxy-3-[2-[4-(trifluoromethyl)phenyl]ethoxy]benzaldehyde (650 mg, 2.00 mmol) in anhydrous tetrahydrofuran (5 mL) was added dropwise and then the mixture was stirred for 1 hour under cooling with ice and for 4 hours at room temperature. Cooled 0.5 mol/L hydrochloric acid (30 mL) was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=6:1 v/v) to afford 842 mg (99%) of the title compound as a colorless oily product. Mass analysis m/z 422 (M+).
  • 33
  • [ 17145-91-4 ]
  • [ 99-90-1 ]
  • (E/Z)-ethyl 3-(4-bromophenyl)-2-ethyl-but-2-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% In tetrahydrofuran; diethyl ether; n-heptane; mineral oil 96.a (E)-(S)-Ethyl 3-{4-[3-(4-Bromophenyl)-2-ethyl-but-2-enyloxy]-phenyl}-2-ethoxy-propionate a) A solution of triethyl 2-phosphonobutyrate (17.7 g, 70.0 mmol) in dry THF (30 ml) was added dropwise, at 0° C., to a stirred suspension of sodium hydride (50% dispersion in mineral oil, 2.90 g, 60.4 mmol) in dry THF (30 ml) and the mixture stirred for 30 min. A solution of 4-bromoacetophenone (7.96 g, 39.99 mmol) in THF (80 ml) was added over 20 min., the resulting mixture warmed to room temperature and stirring continued overnight. Second portions of triethyl 2-phosphonobutyrate (10.11 g, 40.1 mmol) and sodium hydride (2.90 g, 60.4 mmol) were then added at room temperature, and stirring continued for a further 24 h; TLC at this stage showed that a substantial amount of unreacted 4-bromo acetophenone starting material was still present. The reaction was worked up by adding 1N HCl (200 ml) and ethyl acetate (100 ml), the organic layer collected and the aqueous layer extracted with ethyl acetate (3*100 ml). The combined organic layers were washed with brine, dried (MgSO4) and concentrated to give an orange gum, which was purified by column chromatography on silica gel (2% diethyl ether in n-heptane eluent) to give the orange oil, (E/Z)-ethyl 3-(4-bromophenyl)-2-ethyl-but-2-enoate (3.47 g, 29%) as a mixture of double-bond isomers.
  • 34
  • [ 17145-91-4 ]
  • [ 584-08-7 ]
  • [ 3070-65-3 ]
YieldReaction ConditionsOperation in experiment
With formaldehyd In water 7 Ethyl 2-Methylenebutyrate PREPARATION 7 Ethyl 2-Methylenebutyrate A mixture of 5.0 g (0.019 mol) of triethyl 2-phosphonobutyrate, 5.5 g (0.039 mol) of K2 CO3, 6.2 g (0.076 mol) of 37% aqueous formaldehyde solution, and 15 mL of water was heated to about 80° C. for about 45 min. After cooling to RT, 75 mL of ether was added and the organic layer was separated, washed with brine (1*20 mL), dried (MgSO4), and filtered. The ether was carefully removed by distillation, leaving behind 2.1 g (87%) of the title compound as a clear oil which was used directly without further purification. 1 H NMR (CDCl3): 67 1.01 (3H, t, J=7), 1.24 (3H, t, J=7), 2.26 (2H, q, J=7), 4.14 (2H, q, J=7), 5.45 (1H, s), 6.06 (1H, s).
With formaldehyd In water 7 Ethyl 2-Methylenebutyrate PREPARATION 7 Ethyl 2-Methylenebutyrate A mixture of 5.0 g (0.019 mol) of triethyl 2-phosphonobutyrate, 5.5 g (0.039 mol) of K2 CO3, 6.2 g (0.076 mol) of 37% aqueous formaldehyde solution, and 15 mL of water was heated to about 80° C. for about 45 min. After cooling to RT, 75 mL of ether was added and the organic layer was separated, washed with brine (1*20 mL), dried (MgSO4), and filtered. The ether was carefully removed by distillation, leaving behind 2.1 g (87%) of the title compound as a clear oil which was used directly without further purification. 1 H NMR (CDCl3): δ 1.01 (3H, t, J=7), 1.24 (3H, t, J=7), 2.26 (2H, q, J=7), 4.14 (2H, q, J=7), 5.45 (1H, s), 6.06 (1H, s).
With formaldehyd In water 5 Ethyl 2-Methylenebutyrate PREPARATION 5 Ethyl 2-Methylenebutyrate A mixture of 5.0 g (0.019 mol) of triethyl 2-phosphonobutyrate, 5.5 g (0.039 mol) of K2 CO3, 6.2 g (0.076 mol) of 37% aqueous formaldehyde solution, and 15 ml of water was heated to about 80° C. for about 45 min. After cooling to RT, 75 ml of ether was added and the organic layer was separated, washed with brine (1*20 ml), dried (MgSO4), and filtered. The ether was carefully removed by distillation, leaving behind 2.1 g (87%) of the title compound as a clear oil which was used directly without further purification. 1 H NMR (CDCl3): δ 1.01 (3H, t, J=7), 1.24 (3H, t, J=7), 2.26 (2H, q, J=7) 4.14 (2H, q, J=7), 5.45 (1H, s), 6.06 (1H, s).
With formaldehyd In water 7 Ethyl 2-Methylenebutyrate PREPARATION 7 Ethyl 2-Methylenebutyrate A mixture of 5.0 g (0.019 mol) of triethyl 2-phosphonobutyrate, 5.5 g (0.039 mol) of K2 CO3, 6.2 g (0.076 mol) of 37% aqueous formaldehyde solution, and 15 mL of water was heated to about 80° C. for about 45 min. After cooling to RT, 75 mL of ether was added and the organic layer was separated, washed with brine (1*20 mL), dried (MgSO4), and filtered. The ether was carefully removed by distillation, leaving behind 2.1 g (87%) of the title compound as a clear oil which was used directly without further purification. 1 H NMR (CDCl3): δ 1.01 (3 H, t, J=7), 1.24 (3 H, t, J=7), 2.26 (2 H, q, J=7), 4.14 (2 H, q, J=7), 5.45 (1 H, s), 6.06 (1 H, s).

  • 35
  • [ 17145-91-4 ]
  • [ 116993-95-4 ]
  • [ 6674-22-2 ]
  • [ 130980-99-3 ]
YieldReaction ConditionsOperation in experiment
With lithium chloride In tetrahydrofuran b (b) (b) 3-[(4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-4-isobutyloxazolidin-5-yl]-2-ethyl-2-propenoic acid isobutylamide 71.6 mg of lithium chloride was suspended in 5 ml of dry THF under an argon atmosphere, and 426 mg of ethyl 2-diethylphosphonobutanoate dissolved in 0.6 ml of dry THF was added thereto under stirring. The mixture was stirred at room temperature for 5 minutes, and then 323 mg of 1,8-diazabicyclo[5,4,0]-7-undecene (hereinafter referred to simply as DBU) was added thereto in the form of a 50% dry THF solution, and the mixture was stirred at room temperature for 10 minutes. Then, 450 mg of (4S,5R)-3-benzyloxycarbonyl-2,2-dimethyl-5-formyl-4-isobutyloxazolidine dissolved in 1.0 ml of dry THF was added thereto, and the mixture was stirred at room temperature overnight. The reaction solution was cooled to 0° C. and neutralized with 1N hydrochloric acid. Then, the solution was extracted three times with ethyl acetate. The organic layer was washed with water and with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=10/1) to obtain 518 mg of ethyl 3-[(4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-4-isobutyloxazolidin-5-yl]-2-ethyl-2-propenoate as colorless oily substance. Rf: 0.53 (n-hexane/ethyl acetate=5/1). δNMR (60 MHz, CDCl3).
  • 36
  • sodium hydride(content 63%) [ No CAS ]
  • [ 17145-91-4 ]
  • [ 75986-48-0 ]
YieldReaction ConditionsOperation in experiment
With sodium chloride; sodium hydrogencarbonate In tetrahydrofuran; cyclohexane; ethyl acetate 2 (E)-2-Ethyl-3-[4-(3-pyridylmethyl)phenyl]acrylic acid ethyl ester EXAMPLE 2 (E)-2-Ethyl-3-[4-(3-pyridylmethyl)phenyl]acrylic acid ethyl ester To a suspension of 46 mg of sodium hydride(content 63%) in 3 ml of tetrahydrofuran was added dropwise 0.33 g of diethyl 1-ethoxycarbonylpropylphosphonate at room temperature, and the mixture was stirred at that temperature for 15 minutes. To it was added a solution of 206 mg of the aldehyde (prepared as described in Reference Example 1) in one ml, and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was acidified with acetic acid, and concentrated under reduced pressure. To the residue was added a saturated aqueous solution of sodium bicarbonate, and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate (2:1) as eluent to give 273 mg of the title compound having the following physical characteristics: TLC(cyclohexane:ethyl acetate=1:2): Rf=0.33; IR: ν=2980, 1707, 1629, 1475, 1421, 1303, 1284, 1237, 1208, 1127, 1048, 1028, 1020, 712 cm-1; NMR: δ=8.5(2H,m), 7.66(1H,s), 7.53(1H,dt), 7.5-7.1(5H,m), 4.31(2H,q), 4.02(2H,s), 2.58(2H,q), 1.36(3H,t), 1.18(3H,t); MS: m/e=295, 223, 222, 129, 128, 115, 93, 92, 65.
  • 37
  • (4S,5RS)-3-benzyloxycarbonyl-4-cyclohexylmethyl-5-formyl-2,2-dimethyloxazolidine [ No CAS ]
  • [ 17145-91-4 ]
  • ethyl 3-[(4S,5RS)-3-benzyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyloxazolidin-5-yl]-2-ethyl-2-propenoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With lithium chloride In tetrahydrofuran; hexane; ethyl acetate 9.c (3) (c) 176 mg of lithium chloride was suspended in 10 ml of dry tetrahydrofuran, and 834 mg of ethyl 2-diethylphosphonobutanoate was added thereto under an argon stream. The mixture was stirred for 5 minutes at room temperature, and 630 mg of diazabicycloundencene was dropwise added thereto. The mixture was stirred for 10 minutes at room temperature and 10 ml of dry tetrahydrofuran solution of 990 mg of (4S,5RS)-3-benzyloxycarbonyl-4-cyclohexylmethyl-5-formyl-2,2-dimethyloxazolidine obtained in the above step (b) was added thereto and stirred overnight at room temperature. The reaction solution was adjusted to pH 3-4 with 0.5N hydrochloric acid and diluted with water. The solution was extracted with ethyl acetate and the organic layer was washed sequentially with water and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (Kiesel gel 60) by using n-hexane/ethyl acetate (10/1) to obtain 965 mg of ethyl 3-[(4S,5RS)-3-benzyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyloxazolidin-5-yl]-2-ethyl-2-propenoate as a colorless oily substance. Rf: 0.43 (silica gel plate, developer: n-hexane/ethyl acetate (5/1))
  • 38
  • [ 532965-74-5 ]
  • [ 17145-91-4 ]
  • C15H19FO3 [ No CAS ]
  • 39
  • [ 121-32-4 ]
  • [ 17145-91-4 ]
  • [ 935875-45-9 ]
YieldReaction ConditionsOperation in experiment
71% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: 4-hydroxy-3-ethoxybenzaldehyde In tetrahydrofuran at 20℃; for 72h; 33.a a-Ethyl 2-[1-(3-ethoxy-4-hydroxyphenyl)meth-(E)-ylidene]butyrate Example 33Synthesis of 2-[1-[2-ethoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]meth-(E)-ylidene]butyric acid a-Ethyl 2-[1-(3-ethoxy-4-hydroxyphenyl)meth-(E)-ylidene]butyrateA solution of 11.8 g (46 mmol) of triethyl 2-phosphonobutyrate in 20 mL of tetrahydrofuran is added to a mixture of 1.8 g (46 mmol) of sodium hydride in 20 mL of tetrahydrofuran at 0° C. The reaction medium is stirred for 15 minutes. A solution of 3.4 g (20 mmol) of 3-ethoxy-4-hydroxybenzaldehyde prepared as in Example 32a in 20 mL of tetrahydrofuran is then added to the reaction mixture and the reaction medium is stirred at room temperature for 3 days. The reaction medium is then poured into saturated ammonium chloride solution, acidified with aqueous 2 N hydrochloric acid solution and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulfate. The solvent is evaporated off and the residue (12.5 g) is purified by chromatography on a column of silica eluted with an 80/20 heptane/ethyl acetate mixture. 3.7 g (71%) of ethyl 2-[1-(3-ethoxy-4-hydroxyphenyl)meth-(E)-ylidene]butyrate are obtained in the form of a yellow oil.
  • 40
  • [ 398151-09-2 ]
  • [ 17145-91-4 ]
  • [ 935397-41-4 ]
YieldReaction ConditionsOperation in experiment
72% With sodium hydride In tetrahydrofuran at 20℃; 7.a a-Ethyl 2-[1-(3'-methylaminobiphenyl-4-yl)meth-(E)-ylidene]butyrate Example 7Synthesis of 2-[1-[3'-(3-heptyl-1-methylureido)biphenyl-4-yl]meth-(E)-ylidene]butyric acid a-Ethyl 2-[1-(3'-methylaminobiphenyl-4-yl)meth-(E)-ylidene]butyrate197 mg (4.9 mmol) of sodium hydride are added to a mixture of 1.2 mL (4.9 mmol) of triethyl 2-phosphonobutyrate and 415 mg of 3'-methylaminobiphenyl-4-carbaldehyde (2.0 mmol) in 10 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature overnight, poured into saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulfate. The solvent is evaporated off and the residue (1.1 g) is purified by chromatography on a column of silica eluted with a 90/10 heptane/ethyl acetate mixture. 438 mg (72%) of ethyl 2-[1-(3'-methylaminobiphenyl-4-yl)meth-(E)-ylidene]butyrate are obtained in the form of off-white crystals.
  • 41
  • [ 876169-32-3 ]
  • [ 17145-91-4 ]
  • [ 935875-19-7 ]
YieldReaction ConditionsOperation in experiment
97% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran for 0.333333h; Stage #2: 3-butoxy-4-iodobenzaldehyde In tetrahydrofuran at 20℃; for 2.5h; 22.a a-Ethyl 2-[1-(3-butoxy-4-iodophenyl)meth-(E)-ylidene]butyrate Example 22Synthesis of 2-[1-{3'-[(benzoylmethylamino)methyl]-2-butoxybiphenyl-4-yl}meth-(E)-ylidene]butyric acid a-Ethyl 2-[1-(3-butoxy-4-iodophenyl)meth-(E)-ylidene]butyrateA solution of 9 mL (37.8 mmol) of triethyl 2-phosphonobutyrate in 20 mL of tetrahydrofuran is added to a mixture of 1.52 g (37.8 mmol) of sodium hydride in 15 mL of tetrahydrofuran. The reaction medium is stirred for 20 minutes. A solution of 3.83 g (12.6 mmol) of 3-butoxy-4-iodobenzaldehyde (prepared as described in Example 19g) in 15 mL of tetrahydrofuran is then added to the reaction mixture and the reaction medium is stirred at room temperature for 2 hours 30 minutes. The reaction medium is poured into saturated ammonium chloride solution and extracted with ethyl acetate. The organic phases are combined, washed with saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated off and the residue (11.49 g) is purified by chromatography on silica gel eluted with a 95/5 heptane/ethyl acetate mixture. 4.90 g (97%) of ethyl 2-[1-(3-butoxy-4-iodophenyl)meth-(E)-ylidene]butyrate are obtained in the form of a yellow oil that crystallizes.
  • 42
  • [ 742099-09-8 ]
  • [ 17145-91-4 ]
  • ethyl (2E)-3-(2-azepan-1-yl-5-bromophenyl)-2-ethylacrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In toluene at 0 - 20℃; for 1h; Stage #2: 2-(azepan-1-yl)-5-bromobenzaldehyde In toluene for 5h; Heating / reflux; 23 Reference Example 23 Reference Example 23 To a suspension of sodium hydride (60%, 0.39 g) in toluene (10 ml) was added dropwise a solution of ethyl 2-(diethylphosphono)butyrate (2.47 g) in toluene (10 ml) at 0°C under a nitrogen atmosphere. After stirring at room temperature for 1 hour, a solution of 2-azepan-1-yl-5-bromobenzaldehyde (2.3 g) in toluene (20 ml) was added dropwise thereto. The reaction mixture was heated under reflux for 5 hours. Then, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified by column chromatography (ethyl acetate: hexane = 1: 39) to give ethyl (2E)-3-(2-azepan-1-yl-5-bromophenyl)-2-ethylacrylate (2.95 g) as a yellow oily material. 1H-NMR (200 MHz, CDCl3) δ 1.14 (3H, t, J=7.5 Hz), 1.34 (3H, t, J=7.2 Hz), 1.62-1.82 (8H, m), 2.52 (2H, q, J=7.5 Hz), 3.04-3.18 (4H, m), 4.28 (2H, q, J=7.2 Hz), 6.90 (1H, d, J=9.2 Hz), 7.26-7.33 (2H, m), 7.65 (1H, s). IR (neat) 1709, 1480, 1235, 1130, 912, 743 cm-1
  • 43
  • [ 742099-40-7 ]
  • [ 17145-91-4 ]
  • [ 742099-55-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In toluene at 0℃; for 1h; Stage #2: 5-bromo-2-(pyrrolidin-1-yl)benzaldehyde In toluene for 6h; Heating / reflux; 49 Reference Example 49 Reference Example 49 To a suspension of sodium hydride (60%, 0.238 g) in toluene (10 ml) was added dropwise a solution of ethyl 2-(diethylphosphono)butyrate (1.41 ml) in toluene (10 ml) at 0°C under an argon atmosphere. After stirring at 0°C for 1 hour, a solution of 5-bromo-2-pyrrolidin-1-ylbenzaldehyde (1.263 g) in toluene (30 ml) was added thereto, and the mixture was heated under reflux for 6 hours. Water was added to the reaction system, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified by column chromatography (ethyl acetate: hexane 1: 9) to give ethyl (2E)-3-(5-bromo-2-pyrrolidin-1-ylphenyl)-2-ethylacrylate (1.666 g) as a yellow oily material. 1H-NMR (200 MHz, CDCl3) δ 1.10 (3H, t, J=7.3 Hz), 1.34 (3H, t, J=7.1 Hz), 1.87-1.94 (4H, m), 2.48 (2H, q, J=7.3 Hz), 3.17-3.23 (4H, m), 4.27 (2H, q, J=7.1 Hz), 6.65 (1H, d, J=8.8 Hz), 7.20-7.29 (2H, m), 7.62 (1H, s). IR (neat) 1709, 1480, 1236, 1128, 912, 741 cm-1
  • 44
  • [ 2460-58-4 ]
  • [ 17145-91-4 ]
  • [ 874676-66-1 ]
YieldReaction ConditionsOperation in experiment
41% Step 1; Triethyl-2-phosphonobutyrate (2.52 g, 9.99 mmol, 2 equivalents) was dissolved in dryTHF (15 mL) and the solution cooled in an ice bath. NaH (60percent dispersion, 0.41 g,10.2 mmol, 2.0 equivalents) was added in small portions and the white suspensionstirred in the ice bath for 1 h. The hydroxyaldehyde 5-3 from step 2 of Example 5(0.832 g, 5.0 mmol) in THF (10 mL) was added dropwise over 5 min and the ice bathremoved. The mixture was stirred for 20 h at room temperature, after which it wasjudged to be ~60percent complete. The reaction mixture was concentrated under reducedpressure, diluted with EtOAc (40 mL) and washed with NaHCO3 (2 x 20 mL), 10percent HCI(10 mL) and brine (10 mL). The organic layer was dried (Na2SO4), evaporated and the residue purified by flash chromatography to give the desired nitrocinnamate ester(0.365 g, 41percent yield).
  • 45
  • [ 542-28-9 ]
  • [ 17145-91-4 ]
  • ethyl (Z)-2-ethyl-7-hydroxyhept-2-enoate [ No CAS ]
  • ethyl (E)-2-ethyl-7-hydroxyhept-2-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 3,4,5,6-tetrahydro-2H-pyran-2-one With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Warming; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane optical yield given as %de;
  • 47
  • [ 17145-91-4 ]
  • (R)-meta-chlorostyrene oxide [ No CAS ]
  • [ 1241048-49-6 ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane at 25℃; Inert atmosphere; Stage #2: (R)-meta-chlorostyrene oxide In 1,2-dimethoxyethane at 130℃; for 20h; Inert atmosphere; diastereoselective reaction;
  • 48
  • [ 17145-91-4 ]
  • [ 181140-34-1 ]
  • [ 1241048-50-9 ]
  • 49
  • [ 17145-91-4 ]
  • [ 678967-25-4 ]
  • 2-[3-(1-phenyl-vinyl)-1,2,5-trioxa-spiro[5.5]undec-9-ylidene]-butyric acid ethyl ester [ No CAS ]
  • 2-[3-(1-phenyl-vinyl)-1,2,5-trioxa-spiro[5.5]undec-9-ylidene]-butyric acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In 1,2-dimethoxyethane at 0℃; for 1h; Stage #2: 3-(1-Phenyl-vinyl)-1,2,5-trioxaspiro[5.5]undec-9-one In 1,2-dimethoxyethane at 0℃; for 0.5h; 3 To a stirred and cooled (O0C) mixture of NaH (0.04g) in dry dimethoxyethane (15 mL) was added triethylphosphono-2-butyrate (0.3g) and the reaction mixture was stirred at O0C for 1h. To the solution thus obtained was added dropwise a solution of keto trioxane 3a (0.2g) in dry dimethoxyethane (8 mL), while maintaining the temperature of the flask at O0C. After the addition was complete the resulting solution was stirred for additional half an hour at O0C. The reaction mixture was worked up as above and concentrated. The crude product was purified by column chromatography on silica gel to furnish spiro trioxane 4ca (oil, 0.22g, 81% yield) as a mixture of E and Z isomers.
  • 50
  • [ 17145-91-4 ]
  • diethyl 2-hydroxy-1-ethylethylphosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With diborane In tetrahydrofuran at -20 - 20℃; Inert atmosphere;
  • 51
  • [ 17145-91-4 ]
  • [ 6630-33-7 ]
  • C13H15BrO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: ortho-bromobenzaldehyde In tetrahydrofuran at 0 - 20℃; for 18h; 34.1 Example 34Synthesis of N-[(E)-3-(3'-hydroxy-biphenyl-2-yl)-2-ethyl-acryloyl]-guanidineNaH (97.3 mg, 2.43 mmol) was suspended in THF (10 mL) and then cooled to 0° C. 2-phosphono butyric acid triethyl (613 mg, 2.43 mmol) in THF (3 mL) was added dropwise in a slow manner to the solution and then stirred for 15 minutes. Then, 2-bromobenzaldehyde (300 mg, 1.62 mmol) in THF (3 mL) was added thereto in a slow manner and then stirred for 18 hours while gradually heating it from 0° C. to room temperature. EtOAc was added to the reaction solution, washed with water and saturated saline and then dried over anhydrous MgSO4. The solvent was eliminated in vacuo to obtain a residue. The residue obtained was dissolved in THF (10 mL) and MeOH (2 mL), 2 N NaOH (4 mL, 8.0 mmol) was added and then stirred at 50° C. for 8 hours. The solvent was eliminated in vacuo, 2N HCl was added to acidify the solution and then the precipitated crystals were filtrated to obtain white crystals of the objective carboxylic acid (364 mg, 88.4%).1H-NMR (d-DMSO, 300 MHz) ς 1.13 (t, 3H, J=7.3 Hz), 2.40 (q, 2H, J=7.3 Hz), 7.16-7.39 (m, 4H), 7.63 (d, 1H, J=8.2 Hz), 7.78 (s, 1H)MS: 255
  • 52
  • [ 17145-91-4 ]
  • [ 16588-34-4 ]
  • [ 1297549-33-7 ]
YieldReaction ConditionsOperation in experiment
92.1% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0℃; Stage #2: 4-chloro-3-nitro-benzaldehyde In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at -10 - 20℃; 28A Example 28AEthyl(2E/Z)-2-(4-chloro-3-nitrobenzylidene)butanoate; 1.19 g of sodium hydride (60% suspension in mineral oil, 29.64 mmol) were suspended in 50 ml of a THF/DMF mixture (1:1). The mixture was cooled to 0° C., and 7.3 ml (30.99 mmol) of triethyl 2-phosphonobutyrate were added dropwise. After 30 min, 5.0 g (26.94 mmol) of 4-chloro-3-nitrobenzaldehyde were added a little at a time at -10° C. After the addition had ended, the reaction mixture was stirred at 0° C. for 5 h and then slowly warmed to RT overnight. The reaction mixture was then added to water. The mixture was extracted three times with ethyl acetate, and the combined organic phases were concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1). This gave 7.05 g (92.1% of theory) of the target product as an E/Z isomer mixture.LC-MS (Method 6): Rt=1.24 min and 1.26 min; no ionization.
  • 53
  • [ 17145-91-4 ]
  • [ 160744-60-5 ]
  • [ 1312612-97-7 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: triethyl 2-ethylphosphonoacetate With potassium <i>tert</i>-butylate In tetrahydrofuran Inert atmosphere; Cooling with ice; Stage #2: 4-((tert-butyldimethylsilyloxy)methyl)benzaldehyde In tetrahydrofuran at 0 - 20℃; Inert atmosphere; 4.2.48. 2-[4-(tert-Butyl-dimethyl-silanyloxymethyl)benzylidene]butyric acid ethyl ester (33) Potassium t-butoxide (1.63 g, 14.5 mmol) was suspended in dehydrated THF (5 mL) under Ar and cooled with ice. Trimethyl 2-phosphonobutyrate (3.44 mL, 14.5 mmol) was added dropwise. When the addition was completed, the mixture was stirred for 5 min, then compound 32 (3.52 g, 14.06 mmol) dissolved in dehydrated THF (20 mL) was added dropwise at 0 °C. The mixture was stirred for 15 min at rt, then poured into water (40 mL) and extracted with EtOAc (45 mL × 3). The organic layer was washed with H2O (20 mL × 2) and brine (20 mL), and dried over MgSO4. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography to give the target compound (4.67 g, 95%) as a colorless oil.1H NMR (500 MHz, CDCl3) major δ: 7.34 (s, 4H), 4.76 (s, 2H), 4.28 (q, 2H, J = 7.3 Hz), 2.55 (q, 2H, J = 7.3 Hz), 1.35 (t, 3H, J = 7.3 Hz), 1.18 (t, 3H, J = 7.3 Hz), 0.95 (s, 9H), 0.11 (s, 6H). minor δ: 7.23 (s, 2H), 7.21 (s, 2H), 4.72 (s, 2H), 4.14 (q, 2H, J = 7.9 Hz), 2.44 (q, 2H, J = 7.9 Hz), 1.13 (t, 3H, J = 7.3 Hz), 0.93 (s, 9H), 0.09 (s, 6H). FAB-MS m/z: 348 [M]+, 349 [M+H]+.
  • 54
  • [ 17145-91-4 ]
  • [ 56859-93-9 ]
  • [ 1331771-27-7 ]
YieldReaction ConditionsOperation in experiment
50% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 3-(furan-3-yl)propionaldehyde In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; water; mineral oil Inert atmosphere; stereoselective reaction; (E)-4-Furan-3-ylmethylhex-2-enoic acid ethyl ester (29) (Et2O)P(O)CH(Et)COOEt (0.18 mL, 0.75 mmol) was added to the suspension of NaH (60 wt% in oil, 29.9 mg, 0.75 mmol) in THF (6.2 mL) at 0 °C. Then 3-(furan-3-yl)propionaldehyde (77.5 mg, 0.62 mmol) was added to the reaction mixture after 5 min with stirring, and the whole mixture was stirred for 15 min at rt. Sat. NH4Cl aq. was added to the mixture, and the whole mixture was extracted with AcOEt. Removal of the solvent from the AcOEt extract under reduced pressure gave a crude product, which was purified with SiO2 column (n-hexane/AcOEt = 30:1) to give 29(69.2 mg, 50%) as a colorless oil.
  • 55
  • [ 78-85-3 ]
  • [ 17145-91-4 ]
  • C10H16O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydride In dimethyl sulfoxide at 20℃;
  • 56
  • [ 50-00-0 ]
  • [ 17145-91-4 ]
  • [ 3070-65-3 ]
YieldReaction ConditionsOperation in experiment
66% With sodium hydride In N,N-dimethyl-formamide at 20℃;
With potassium carbonate In water at 85℃; for 0.75h; 16.1 [Step 1] Ethyl 2-methylenebutyrate Potassium carbonate (5.5 g) was dissolved in water (15 mL). To the solution, ethyl 2-(diethoxyphosphoryl)butyrate (5.0 g) and a 37% aqueous formaldehyde (6.2 g) were added at room temperature, and the mixture was stirred at 85°C for 45 minutes. Organic matter was extracted with diethyl ether, dried over anhydrous sodium sulfate, and filtered, and the solvent in the filtrate was distilled off under reduced pressure to obtain a crude product. 1H-NMR (CDCl3) δ: 1.08 (3H, t, J = 7.4 Hz), 1.31 (3H, t, J = 7.0 Hz), 2.30-2.36 (2H, m), 4.21 (2H, q, J = 7.0 Hz), 5.51-5.52 (1H, m), 6.12-6.14 (1H, m).
  • 57
  • 5-methoxy-2-nitroso-N-(4-methylphenyl)aniline [ No CAS ]
  • [ 17145-91-4 ]
  • 3-ethyl-7-methoxy-1-(4-methylphenyl)quinoxalin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In acetonitrile at 20℃; for 20h;
  • 58
  • [ 98-01-1 ]
  • [ 17145-91-4 ]
  • [ 53282-12-5 ]
YieldReaction ConditionsOperation in experiment
82% With potassium carbonate In ethanol at 70℃; for 2h; 1 4.1.1 (E)-Ethyl 3-(furan-2-yl)acrylate (6) Furfural (5, 0.1mol, 8.28mL) in absolute ethanol (10mL) was added in one portion to a mixture of triethyl 2-phosphonobutyrate (0.12 mol, 23.8 mL) and anhydrous potassium carbonate (0.3 mol, 41.4 g) in absolute ethanol (100 mL). After being stirred at 70°C for 2h, the reaction mixture was cooled to room temperature, filtrated and washed with ethanol (2×20 mL). The filtrate was concentrated and distilled under reduced pressure to give pure yellowish solid (13.6 g) in 82% yield; mp 24-26°C [lit.51 24°C].
  • 59
  • [ 17145-91-4 ]
  • [ 2439-43-2 ]
  • C16H22O2 [ No CAS ]
  • C16H22O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
60 % de Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: (2RS)-2-phenylbutanal In tetrahydrofuran for 14h; Overall yield = 152 mg; 2.1 Production Example 2 Synthesis of Compounds 5 and 6 Further, sodium hydride (purity 55%, 90.7 mg) was similarly suspended in tetrahydrofuran (7 mL) , triethyl 2-phosphonobutyrate (0.62 mL) was added thereto and the solution was stirred for 30 minutes at room temperature under nitrogen atmosphere. A solution of aldehyde (e) (154 mg) dissolved in tetrahydrofuran (2 mL) was added to the reaction solution and further stirred for 14 hours. An aqueous solution of saturated ammonium chloride and hexane were added to the reaction solution and the hexane layer was dried under reduced pressure and subsequently purified by silica gel chromatography, thereby obtaining an ,β unsaturated ester (g) (E/Z = 1 : 4, 152 mg) .
60 % de Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: (2RS)-2-phenylbutanal In tetrahydrofuran for 14h; Overall yield = 152 mg; 2.1 Further, sodium hydride (purity 55%, 90.7 mg) was similarly suspended in tetrahydrofuran (7 mL), triethyl 2-phosphonobutyrate (0.62 mL) was added thereto and the solution was stirred for 30 minutes at room temperature under nitrogen atmosphere. A solution of aldehyde (e) (154 mg) dissolved in tetrahydrofuran (2 mL) was added to the reaction solution and further stirred for 14 hours. An aqueous solution of saturated ammonium chloride and hexane were added to the reaction solution and the hexane layer was dried under reduced pressure and subsequently purified by silica gel chromatography, thereby obtaining an α,β unsaturated ester (g) (E/Z=1:4, 152 mg).
  • 60
  • [ 17145-91-4 ]
  • [ 34713-70-7 ]
  • C15H20O2 [ No CAS ]
  • C15H20O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 35.9 mg 2: 396.4 mg Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 2-Phenylpropanal In tetrahydrofuran for 15h; 1.1 Production Example 1 Synthesis of Compounds 2 to 4 (1) Sodium hydride (purity 55%, 195 mg) was suspended in tetrahydrofuran (15 mL) , triethyl 2-phosphonobutyrate(1.33 mL) was added thereto and the solution was stirred for 30 minutes at room temperature under nitrogenatmosphere. A solution of 2-phenylpropionaldehyde (a)(300 mg) dissolved in tetrahydrofuran (5 mL) was added to the reaction solution and further stirred for 15 hours. An aqueous solution of saturated ammonium chloride and hexane were added to the reaction solution and the hexane layer was dried under reduced pressure and subsequently purified by silica gel chromatography, thereby obtaining(Ε)-α,β unsaturated ester (b) (35.9 mg) and (Ζ)-α,β unsaturated ester (c) (396.4 mg) .
1: 35.9 mg 2: 396.4 mg Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 2-Phenylpropanal In tetrahydrofuran for 15h; 1.1; 1 Sodium hydride (purity 55%, 195 mg) was suspended in tetrahydrofuran (15 mL), triethyl 2-phosphonobutyrate (1.33 mL) was added thereto and the solution was stirred for 30 minutes at room temperature under nitrogen atmosphere. A solution of 2-phenylpropionaldehyde (a) (300 mg) dissolved in tetrahydrofuran (5 mL) was added to the reaction solution and further stirred for 15 hours. An aqueous solution of saturated ammonium chloride and hexane were added to the reaction solution and the hexane layer was dried under reduced pressure and subsequently purified by silica gel chromatography, thereby obtaining (E)-α,β unsaturated ester (b) (35.9 mg) and (Z)-α,β unsaturated ester (c) (396.4 mg).
  • 61
  • [ 96-09-3 ]
  • [ 17145-91-4 ]
  • [ 1147818-06-1 ]
YieldReaction ConditionsOperation in experiment
63% With n-butyllithium In 1,2-dimethoxyethane at 20 - 130℃; for 1.33333h; Inert atmosphere; Microwave irradiation; A-1 Ethyl (1 S,2R)-1 -ethyl-2-phenyl-cvclopropanecarboxylate 2.5 mL (2.5 mol/L) buthyl lithium was added to a solution of 1.5 g (5.4 mmol) ethyl 2- diethoxyphosphorylbutanoate (Sigma Aldrich) in 5 mL dry DME under N2 atmosphere at RT. After 5 min, 0.50 g (4.2 mmol) styrene epoxide (Sigma Aldrich) was added dropwise. The mixture was stirred for 20 min at RT and then heated at 130°C under MW irradiation for 1 h. Aqueous NH4CI was added, and the product was extracted with CH2CI2. The combined organic layers were dried over MgS04 and concentrated. The dry residue was purified by column chromatography (eluent: EtOAc/hexane, 0:100 to 10:100) to give ethyl (1 S,2R)-1 -ethyl-2-phenyl-cyclopropanecarboxylate (570 mg, 63%) as a colorless oil. 1H NMR (CDCI3) δ (ppm): 7.35-7.16 (m, 5 H), 4.32-4.05 (m, 2 H), 2.89-2.75 (m, 1 H), 1 .73-1.58 (m, 2 H), 1.30 (t, J=7.1 Hz, 3 H), 1.20-1.14 (m, 1 H), 1.06-0.79 (m, 4 H).
63% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: styrene oxide In 1,2-dimethoxyethane at 20 - 130℃; for 1.33333h; Microwave irradiation; A-1 Ethyl (1S,2R)-1-ethyl-2-phenyl-cyclopropanecarboxylate Ethyl (1S,2R)-1-ethyl-2-phenyl-cyclopropanecarboxylate 2.5 mL (2.5 mol/L) buthyl lithium was added to a solution of 1.5 g (5.4 mmol) ethyl 2-diethoxyphosphorylbutanoate (Sigma Aldrich) in 5 mL dry DME under N2 atmosphere at RT. After 5 min, 0.50 g (4.2 mmol) styrene epoxide (Sigma Aldrich) was added dropwise. The mixture was stirred for 20 min at RT and then heated at 130°C under MW irradiation for 1 h. Aqueous NH4Cl was added, and the product was extracted with CH2Cl2. The combined organic layers were dried over MgSO4 and concentrated. The dry residue was purified by column chromatography (eluent: EtOAc/hexane, 0:100 to 10:100) to give ethyl (1S,2R)-1-ethyl-2-phenyl-cyclopropanecarboxylate (570 mg, 63%) as a colorless oil. 1H NMR (CDCl3) δ (ppm): 7.35-7.16 (m, 5 H), 4.32-4.05 (m, 2 H), 2.89-2.75 (m, 1 H), 1.73-1.58 (m, 2 H), 1.30 (t, J=7.1 Hz, 3 H), 1.20-1.14 (m, 1 H), 1.06-0.79 (m, 4 H).
  • 62
  • [ 32017-76-8 ]
  • [ 17145-91-4 ]
  • ethyl trans-1-ethyl-2-(4-bromophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With n-butyllithium; In 1,2-dimethoxyethane; at 20 - 135℃; for 1.33333h;Inert atmosphere; Microwave irradiation; 2.4 mL (2.5 mol/L) buthyl lithium was added to a solution of 1 .5 g (5.4 mmol) ethyl 2- diethoxyphosphorylbutanoate (Sigma Ald ch) in 5 mL dry DME under N2 atmosphere at RT. After 5 min, 1 .0 g (5.0 mmol) <strong>[32017-76-8]2-(4-bromophenyl)oxirane</strong> (Sigma Aldrich) was added dropwise. The mixture was stirred for 20 min at RT and then heated at 135C under MW irradiation for 1 h. Aqueous NH4CI was added, and the product was extracted with CH2CI2. The combined organic layers were dried over MgS04 and concentrated. The dry residue was purified by column chromatography (eluent: EtOAc/hexane, 0: 100 to 10: 100) to give ethyl trans^ -ethyl-2-(4-bromophenyl)-cyclopropanecarboxylate (910 mg, 61 %) as a colorless oil. 1 H NMR (CDCI3) delta (ppm): 7.44-7.40 (m, 2H) 7.10-7.06 (m, 2H), 4.29-4.1 1 (m, 2 H), 2.80-2.69 (m, 1 H), 1 .70-1 .63 (m, 1 H), 1 .62-1 .51 (m, 1 H), 1 .30 (t, J=7.1 Hz, 3 H), 1 .14-1 .10 (m, 1 H) 0.98-0.82 (m, 4 H).
  • 63
  • [ 32017-76-8 ]
  • [ 17145-91-4 ]
  • ethyl trans-1-ethyl-2-(4-bromophenyl)-cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% Ethyl trans-1-ethyl-2-(4-bromophenyl)-cyclopropanecarboxylate 2.4 mL (2.5 mol/L) buthyl lithium was added to a solution of 1.5 g (5.4 mmol) ethyl 2-diethoxyphosphorylbutanoate (Sigma Aldrich) in 5 mL dry DME under N2 atmosphere at RT. After 5 min, 1.0 g (5.0 mmol) <strong>[32017-76-8]2-(4-bromophenyl)oxirane</strong> (Sigma Aldrich) was added dropwise. The mixture was stirred for 20 min at RT and then heated at 135C under MW irradiation for 1 h. Aqueous NH4Cl was added, and the product was extracted with CH2Cl2. The combined organic layers were dried over MgSO4 and concentrated. The dry residue was purified by column chromatography (eluent: EtOAc/hexane, 0:100 to 10:100) to give ethyl trans-1-ethyl-2-(4-bromophenyl)-cyclopropanecarboxylate (910 mg, 61 %) as a colorless oil 1H NMR (CDCl3) delta(ppm): 7.44-7.40 (m, 2H) 7.10-7.06 (m, 2H), 4.29-4.11 (m, 2 H), 2.80-2.69 (m, 1 H), 1.70-1.63 (m, 1 H), 1.62-1.51 (m, 1 H), 1.30 (t, J=7.1 Hz, 3 H), 1.14-1.10 (m, 1 H) 0.98-0.82 (m, 4 H).
  • 64
  • [ 96-09-3 ]
  • [ 17145-91-4 ]
  • (trans)-ethyl 1-ethyl-2-phenylcyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: styrene oxide In 1,2-dimethoxyethane at 20 - 130℃; for 1.83333h; Inert atmosphere; Microwave irradiation; 4.1.1.1 Ethyl (1R,2S)-1-methyl-2-phenyl-cyclopropanecarboxylate (11a) General procedure: 5.6mL (2.5mol/L) butyl lithium was added to a solution of 3.4g (14mmol) ethyl 2-diethoxyphosphorylbutanoate (Sigma Aldrich) in 12mL dry DME under N2 atmosphere at RT. After 5min, 1.3g (11mmol) (2S)-2-phenyloxirane (Sigma Aldrich) was added dropwise. The mixture was stirred for 20min at RT and then heated at 130°C under MW irradiation for 90min. Aqueous NH4Cl was added and the product was extracted with Et2O. The combined organic layers were dried over Na2SO4 and concentrated. The dry residue was purified by column chromatography (eluent: EtOAc/hexane, 0:100-10:100) to give the ethyl cyclopropanecarboxylate 11a (2.9g, 90%).
Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: styrene oxide In 1,2-dimethoxyethane; hexane at 90℃; for 18h;
  • 65
  • [ 17145-91-4 ]
  • [ 20780-53-4 ]
  • [ 1147818-06-1 ]
YieldReaction ConditionsOperation in experiment
63% General procedure: 5.6mL (2.5mol/L) butyl lithium was added to a solution of 3.4g (14mmol) ethyl 2-diethoxyphosphorylbutanoate (Sigma Aldrich) in 12mL dry DME under N2 atmosphere at RT. After 5min, 1.3g (11mmol) (2S)-2-phenyloxirane (Sigma Aldrich) was added dropwise. The mixture was stirred for 20min at RT and then heated at 130C under MW irradiation for 90min. Aqueous NH4Cl was added and the product was extracted with Et2O. The combined organic layers were dried over Na2SO4 and concentrated. The dry residue was purified by column chromatography (eluent: EtOAc/hexane, 0:100-10:100) to give the ethyl cyclopropanecarboxylate 11a (2.9g, 90%).
  • 66
  • [ 28022-44-8 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(3-bromophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 2-(3-bromophenyl)oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 67
  • [ 20697-04-5 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(3-chlorophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 3-chlorostyrene oxide In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 68
  • [ 32017-76-8 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(4-bromophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: (+/-)-2-(4-bromophenyl)oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 69
  • [ 18511-63-2 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(3-fluorophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 3-fluorophenylethylene oxide In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 70
  • [ 17145-91-4 ]
  • [ 2788-86-5 ]
  • ethyl 1-ethyl-2-(4-chlorophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 4-Chlorostyrene oxide In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 71
  • [ 1428-54-2 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(3-trifluoromethylphenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: rac-2-(3-trifluoromethylphenyl)-oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 72
  • [ 32017-77-9 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(3-methoxyphenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 2-(m-methoxyphenyl)oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 73
  • 4-fluorostyrene oxide [ No CAS ]
  • [ 17145-91-4 ]
  • ethyl 2-(4-fluorophenyl)-1-ethyl-cyclopropane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 4-fluorostyrene oxide In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 74
  • [ 17145-91-4 ]
  • [ 111991-14-1 ]
  • ethyl 1-ethyl-2-(4-(trifluoromethyl)phenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 2-(4-trifluoromethylphenyl)oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 75
  • [ 17145-91-4 ]
  • [ 62717-50-4 ]
  • ethyl 1-ethyl-2-(2-chlorophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: o-chlorostyrene oxide In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 76
  • [ 17145-91-4 ]
  • [ 71636-51-6 ]
  • ethyl 1-ethyl-2-(2-bromophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 2-(2-bromophenyl)oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 77
  • [ 17145-91-4 ]
  • 2-fluorophenylethylene oxide [ No CAS ]
  • ethyl 1-ethyl-2-(2-fluorophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 2-fluorophenylethylene oxide In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 78
  • [ 17145-91-4 ]
  • [ 1400997-35-4 ]
  • ethyl 1-ethyl-2-(3-fluoro-4-bromophenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: (RS)-2-(4-bromo-3-fluorophenyl)-oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 79
  • [ 111991-17-4 ]
  • [ 17145-91-4 ]
  • ethyl 1-ethyl-2-(4-(trifluoromethoxy)phenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: triethyl 2-ethylphosphonoacetate With n-butyllithium In 1,2-dimethoxyethane; hexane at 25℃; for 0.583333h; Stage #2: 2-(4-trifluoromethoxy-phenyl)-oxirane In 1,2-dimethoxyethane; hexane at 90℃; 4.3.2. General procedure for the cyclopropanation (2-15a, 4b,2,4,6,9c, 2,3,4,9d,4,6,9e) To a solution of the appropriate phosphorane (2 eq) in anhydrous DME (5 mL/mmol) at 25 °C, n-buthyllithium (1.6 M in hexanes,2 eq) was added dropwise over 5 min. After stirring for 30 min at the same temperature, the solution turned gradually too range and the appropriate epoxide (1 eq) was added in one portion. The reaction was heated at 90 °C until consumption of the limiting reagent as determined by TLC, and then NH4Cl is added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3 x 15 mL), and the organic layers were washed with brine and dried (Na2SO4). After removal of the solvent in vacuo, the yellowish oil obtained was purified by flash column chromatography to give the title compounds as colourless oil. Yields, purification methods and analytical data are reported in details in the SI.
  • 80
  • [ 17145-91-4 ]
  • [ 659-28-9 ]
  • ethyl 2-[4-(trifluoromethoxy)benzylidene]butyrate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.31 g Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.5h; Cooling with ice; Stage #2: p-trifluoromethoxybenzaldehyde In tetrahydrofuran; mineral oil at 20℃; for 1h; Cooling with ice; 20.A A) To a solution of ethyl 2-(diethoxyphosphoryl)butyrate (1.41 g) in tetrahydrofuran (25 mL) was slowly added 60% sodium hydride (223 mg) under ice cooling. The reaction mixture was stirred at room temperature for 30 min, and a solution of 4-(trifluoromethoxy)benzaldehyde (1.01 g) in tetrahydrofuran (5 mL) was slowly added thereto under ice cooling. The reaction mixture was stirred at room temperature for 1 hr, and poured into water, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give ethyl 2-[4-(trifluoromethoxy)benzylidene]butyrate (1.31 g).
  • 81
  • [ 17145-91-4 ]
  • [ 3695-77-0 ]
  • [ 107-02-8 ]
  • ethyl (E)-2-ethyl-5-(triphenylmethylthio)-2-pentenoate [ No CAS ]
  • ethyl (Z)-2-ethyl-5-(triphenylmethylthio)-2-pentenoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
12 % de With sodium hydride In tetrahydrofuran at 20℃; Flow reactor; Overall yield = 54 %; Overall yield = 278 mg; 6 General procedure for the synthesis of α, β-unsaturated ester 8 and 11a-e in flow General procedure: The flow system was established with a syringe pumps (HII-10B, Techno applications), Teflon tube, the flow reactor (Comet X-01-T, Techno applications), polymer-supported DABCO (2.2 g, 2.3 mmol) packed column flow reactor (20 mm bore×38 mm length). Before use, the flow system was flushed with THF and dried under vacuum. A solution of the trityl thiol (0.4 M) and acrolein (6) (0.56 M) in THF was then loaded into a Teflon sample loop (Tube 1), and a solution of deprotonated HWE reagents (0.52 M) in THF was loaded into another Teflon sample loop (Tube 3). Both two solutions were pumped at flow rate of 2 mL min-1, and mixed in the reactor (Comet X-01-T and Tube 4) at the room temperature. The resulting mixture was quenched by 1 M aqueous HCl, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with hexane/EtOAc=98:2) to give the α,β-unsaturated esters 8 and 11a-e. 4.4.6 Ethyl (E)-2-ethyl-5-(triphenylmethylthio)-2-pentenoate (11e) Collection volume: 6 mL; colorless oil (278 mg, 0.645 mmol, 54%, E/Z=56:44). 1H NMR (400 MHz, CDCl3): δ 7.44-7.38 (m, 6H), 7.32-7.25 (m, 6H), 7.24-7.17 (m, 3H), 6.52 (t, 1H, J=7.2 Hz), 4.16 (q, 2H, J=7.0 Hz), 2.30-2.14 (m, 6H), 1.27 (t, 3H, J=7.0 Hz), 0.92 (t, 3H, J=8.0 Hz); 13C NMR (100 MHz, CDCl3): δ 167.5, 144.7, 139.0, 135.2, 129.5, 127.8, 126.6, 66.7, 60.3, 30.9, 27.6, 20.0, 14.2, 13.8; FTIR (Neat): 3057, 2975, 2933, 2873, 1709, 1489, 1444, 1288, 1288, 1244, 743, 701 cm-1; HRMS (ESI): calcd for C28H30NaO2S [M+Na]+ 453.1864, found 453.1857.
  • 82
  • [ 17145-91-4 ]
  • 4-formyl-N-(2-(trifluoromethyl)benzyl)benzamide [ No CAS ]
  • ethyl (E)-4-[N-(2-(trifluoromethyl)benzyl)benzamide]-α-ethylcinnamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-formyl-N-(2-(trifluoromethyl)benzyl)benzamide In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;
70% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-formyl-N-(2-(trifluoromethyl)benzyl)benzamide In tetrahydrofuran for 2h; General procedure for the preparation of the compounds (la-19a), using the example of ethyl (E)-4-[N-((2-(trifluoromethyl)benzyl)benzamide]-alpha-ethylcinnamate (la). General procedure: To a solution of 156 mg (6.5 mmol) NaH in 5 ml dry THF under an argon atmosphere at 0 °C was added slowly 1.2 ml (4.9 mmol) triethyl 2-phosphonobutyrat. After 30 min a solution of 1 g (3.3 mmol) of 4-formyl-N-(2-(trifluoromethyl)benzyl)benzamide (1) in 10 ml dry THF was added to the reaction mixture and stirred for 2 h. To quench the reaction 25 ml water were used. The resulting mixture was diluted with 10 ml EE. The organic layer was washed three times with brine and dried over MgSCb. The solvent was evaporated under reduced pressure. After recrystallization from EE/Hex a white solid remained. Yield: 0.92 g (70 %); NMR (DMSO- de): δ 9.25 (t, J= 5.8 Hz, 1H, Ph2-OC H), 8.09-7.38 (m, 8H, OC H-Phi+Phi-OC H-CH2-Ph2), 7.67 (s, 1H, OC H-Phi-CH), 4.74 (d, J= 5.4 Hz, 2H, Phi-OC H-CH2), 4.3 (q, J= 7.1 Hz, 2H, C-COO-CH2), 2.4 (q, J= 6.9 Hz, 2H, CH-C-CH2), 1.36 (t, J= 7.06 Hz, 3H, COO-CH2-CH3), 1.18 (t, J= 7.38 Hz, 3 H, C-CH2-CH3) ppm; 13C-NMR (DMSO-): 13C- MR (DMSO-i): 169.4, 167.3, 136.9, 136.5, 136.3, 135.8, 135.7, 131.5, 129.4, 128.8, 128.4, 127.3, 126.3, 125.1, 125, 124.9, 124.1, 60.5, 40.2, 23.7, 13.3, 10 ppm; HRMS: measured m/z 405.1550 (theoretical: 405.1551). [171] Ethyl (E)-4-[N-benzylbenzamide]-alpha-ethylcinnamate (2a). Yield: 0 92 g (65 %); NMR (DMSO-i): δ 9.12 (t, J= 6.1 Hz, 1H, Ph2-OC H), 7.98-7.21 General procedure for the preparation of the compounds (la-19a), using the example of ethyl (E)-4-[N-((2-(trifluoromethyl)benzyl)benzamide]-alpha-ethylcinnamate (la). (m, 9H, OCNH-Phi+Phi- OC H-CH2-Ph2), 7.33 (s, 1H, OC H-Phi-CH), 4.5 (d, J= 5.7 Hz, 2H, Phi-OC H-CH2), 4.23 (q, J= 7 Hz, 2H, C-COO-CH2), 2.41 (q, J= 7 Hz, 2H, CH-C-CH2), 1.3 (t, J= 7.8 Hz, 3H, COO- CH2-CH3), 1.12 (t, J= 7.3 Hz, 3 H, C-CH2-CH3) ppm; 13C- MR (DMSO-^e): 167.5, 165.7, 137.9, 137.5, 137.1, 136.1, 135.9, 131.5, 129, 128.3, 127.5, 127.4, 126.7, 125.6, 125.5, 124.4, 61.7, 39.8, 24.9, 14.2, 10.5 ppm; HRMS: measured m/z 338.1752 (theoretical: 338.1750).
  • 83
  • [ 129242-08-6 ]
  • [ 17145-91-4 ]
  • ethyl (E)-4-[N-benzylbenzamide]-α-ethylcinnamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-formyl-N-(benzyl)benzamide In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;
  • 84
  • [ 17145-91-4 ]
  • 4-formyl-N-(2-(methyl)benzyl)benzamide [ No CAS ]
  • ethyl (E)-4-[N-((2-methyl)benzyl)benzamide]-α-ethylcinnamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-formyl-N-(2-(methyl)benzyl)benzamide In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;
  • 85
  • [ 17145-91-4 ]
  • 4-formyl-N-(2-(bromo)benzyl)benzamide [ No CAS ]
  • ethyl (E)-4-[N-((2-bromo)benzyl)benzamide]-α-ethylcinnamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-formyl-N-(2-(bromo)benzyl)benzamide In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;
  • 86
  • [ 17145-91-4 ]
  • 4-formyl-N-(2-(trifluoromethoxy)benzyl)benzamide [ No CAS ]
  • ethyl (E)-4-[N-((2-trifluoromethoxy)benzyl)benzamide]-α-ethylcinnamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-formyl-N-(2-(trifluoromethoxy)benzyl)benzamide In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;
  • 87
  • [ 17145-91-4 ]
  • [ 79099-07-3 ]
  • tert-butyl 4-(1-ethoxy-1-oxobutan-2-ylidene)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.416667h; Inert atmosphere; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran; mineral oil for 1.5h; 243 A. tert-Butyl 4-( 1 -ethoxy- 1 -oxobutan-2-ylidene)piperidine- 1 -carboxylate To a suspension of NaH (0.29 g, 7.18 mmol) in anhydrous THF (10 mL), under nitrogen atmosphere, was added triethyl 2-phosphonobutyrate (1.81 g, 7.18 mmol) over 5 minutes. The resultant mixture was stirred at ambient temperature for 20 minutes, during which time it became homogeneous. To this solution was added dropwise a homogeneous mixture of l-Boc-4-piperidone (1.10 g, 5.52 mmol) in anhydrous THF (2.5 mL). After stirring for 1.5 hours, the reaction was quenched with saturated NH4C1 (aq) solution before being thoroughly extracted with EtOAc. The organic fractions were combined, washed with brine, dried (MgS04), filtered and concentrated in vacuo to afford tert-butyl 4-(l -ethoxy- l-oxobutan-2-ylidene)piperidine-l -carboxylate a clear oil (1.64 g; 100% yield) which was used without further purification. 1H NMR (400MHz, DMSO-de) δ 4.13 (q, J=7.1 Hz, 2H), 3.39 - 3.35 (m, 2H), 3.35 - 3.31 (m, 2H), 2.45 - 2.39 (m, 2H), 2.31 - 2.22 (m, 4H), 1.40 (s, 9H), 1.21 (t, j=7.2 Hz, 3H), 0.93 (t, j=7.5 Hz, 3H).
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 20℃; for 0.416667h; Inert atmosphere; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran for 1.5h; 20.A 20A. tert-Butyl 4-(l-ethoxy-l-oxobutan-2-ylidene)piperidine-l-carboxylate [00192] To a suspension of NaH (0.29 g, 7.18 mmol) in anhydrous THF (10 mL), under nitrogen atmosphere, was added triethyl 2-phosphonobutyrate (1.81 g, 7.18 mmol) over 5 minutes. The resultant mixture was stirred at ambient temperature for 20 minutes, during which time it became homogeneous. To this solution was added dropwise a homogeneous mixture of l -Boc-4-piperidone (1.10 g, 5.52 mmol) in anhydrous THF (2.5 mL). After stirring for 1.5 hours, the reaction was quenched with saturated NH4C1 (aq) solution before being thoroughly extracted with EtOAc. The organic fractions were combined, washed with brine, dried (0338) (MgS04), filtered and concentrated in vacuo to afford tert-butyl 4-(l -ethoxy-l-oxobutan-2- ylidene)piperi dine- 1 -carboxy late a clear oil (1.64 g; 100% yield) which was used without further purification. XH NMR (400MHz, DMSO-d6) δ 4.13 (q, J=7.1 Hz, 2H), 3.39 - 3.35 (m, 2H), 3.35 - 3.31 (m, 2H), 2.45 - 2.39 (m, 2H), 2.31 - 2.22 (m, 4H), 1.40 (s, 9H), 1.21 (t, J=7.2 Hz, 3H), 0.93 (t, J=7.5 Hz, 3H).
  • 88
  • bicyclohexyl-4-4'-dicarbaldehyde [ No CAS ]
  • [ 17145-91-4 ]
  • 2-[1-[4'-(2-ethoxycarbonyl-but-1-enyl)bicyclohexyl-4-yl]methylidene]butyric acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: bicyclohexyl-4-4'-dicarbaldehyde With lithium bromide In tetrahydrofuran; mineral oil at 20℃; 38.38.1 Triethylphosphonobutyrate (70 ml, 0.289 mol) in THF (1 I) is cooled to 00C. Sodium hydride (60 % in mineral oil, 13.5 g, 0.338 mol) is added and the mixture is stirred for 30 min. Lithium bromide (20 g, 0.230 mol) is added, followed by a suspension of bicyclohexyl-4-4'-dicarbaldehyde (22.5 g, 0.1 mol) in 200 ml of THF. After 6 h the cooling bath is removed and the reaction is stirred at room temp, overnight, lsopropanol is added and the reaction mixture is poured onto water, extracted three times (MTB-ether) and dried (Na2SO4). The solvent is evaporated and the crude product is filtered through silica with heptane/ethyl acetate (10:1) to give 2-[1- [4'-(-2-ethoxycarbonyl-but-1-enyl)-bicyclohexyl-4-yl]- methylidene]-butyric acid ethyl ester as a colourless solid.
  • 89
  • [ 17145-91-4 ]
  • [ 80361-78-0 ]
  • 2-[1-(4-propylcyclohexyl)methylidene]butyric acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: 4-n-propyl-transcyclohexane carbaldehyde With lithium bromide In tetrahydrofuran; mineral oil at 20℃; 46.46.1 Triethylphosphonobutyrate (45 ml, 0.124 mol) in THF (500 ml) is cooled to 00C. Sodium hydride (60 % in mineral oil, 9 g, 0. 225mol) is added and the mixture is stirred for 30 min. Lithium bromide (12.9 g, 0.149 mol) is added, followed by a suspension of cyclohexane-4-carbaldehyde (19 g, 0.124 mol). After 6 h the cooling bath is removed and the reaction mixture is stirred at room temp, overnight, lsopropanol is added and the reaction mixture is poured onto water, extracted three times (MTB-ether) and dried (Na2SO4). The solvent is evaporated and the crude product is filtered through silica with heptane/ethyl acetate (10:1 ) to give 2-[1- (4-propyl-cyclohexyl)-methylidene]-butyric acid ethyl ester as a colourless oil.
  • 90
  • [ 17145-91-4 ]
  • (1R,8R)-5-(2,6-difluoro-phenyl)-11,11-dimethyl-3,4-diaza-tricyclo[6.2.1.02,7]undeca-2(7),3,5-triene-1-carbaldehyde [ No CAS ]
  • ethyl (Z)-2-(((5R,8R)-3-(2,6-difluorophenyl)-9,9-dimethyl-6,7-dihydro-5,8-methanocinnolin-8(5H)-yl)methylene)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
435 mg With sodium hydride In tetrahydrofuran at 0 - 80℃; for 2h; Inert atmosphere; 5 Ethyl (Z)-2-(((5R,8R)-3-(2,6-difluorophenyl)-9,9-dimethyl-6,7-dihydro-5,8-methanocinnolin-8(5H)-yl)methylene)butanoate To a solution of ethyl 2-(diethoxyphosphoryl)butanoate (960 mg, 3.36 mmol) in dry THF (25 mL) was added NaH (152 mg, 3.81 mmol) at 0 °C under nitrogen atmosphere. The mixture was stirred at 0 °C for 1 h, then the product from step 1 (960 mg, 3.05 mmol) in THF (10 mL) was added. The reaction was heated at 80 °C for 2 h, cooled to room temperature, quenched with saturated aqueous NH4C1 (40 mL), extracted with EtOAc (2 x 60 mL), dried (Na2S04)_ and purified by chromatography (0-25% EtOAc- petroleum ether) to afford the title compound as a yellow solid (435 mg). LCMS (ESI): m/z = 413.2 [M+H]+.
  • 91
  • [ 17145-91-4 ]
  • [ 15174-47-7 ]
  • (2E,4E)-ethyl 2-ethyl-4-methyl-5-phenylpenta-2,4-dienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.333333h; Stage #2: α-methyl-trans-cinnamaldehyde In tetrahydrofuran; mineral oil at 0 - 20℃; for 12h; 1 (2E,4E)-ethyl 2-ethyl-4-methyl-5-phenylpenta-2,4-dienoate To a solution of sodium hydride (60% dispersion in mineral oil, 351 mg, 8.82 mmol) in tetrahydrofuran (12 mL) at 0°C, triethyl phosphonoacetate (2.12 g, 8.40 mmol) was added dropwise. The mixture was stirred at 0 °C for 20 minutes. Then, trans-alpha- methylcinnamaldehyde (1.35 g, 9.24 mmol) was added dropwise at 0 °C. The reaction was stirred at room temperature for 12 hours and quenched with brine. The solution was concentrated to 1/3 of the original volume under reduced pressure. The aqueous layer was extracted with methylene chloride and the combined organic layers were dried over Na2S04. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel to give (2E,4E)-ethyl 2-ethyl-4-methyl-5-phenylpenta-2,4- dienoate (1.77 g, 7.24 mmol) in quantitative yield. LCMS (ESI+): 245.6 (M+H)
  • 92
  • [ 17145-91-4 ]
  • [ 67858-78-0 ]
  • C23H38O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
39.4% With n-butyllithium In tetrahydrofuran; hexane at 20℃; for 0.5h; Inert atmosphere;
With n-butyllithium at 20℃; Inert atmosphere;
  • 93
  • [ 17145-91-4 ]
  • [ 100-52-7 ]
  • [ 60754-33-8 ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: benzaldehyde In tetrahydrofuran at 0 - 20℃; for 12h;
62% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: benzaldehyde In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere;
Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: benzaldehyde In tetrahydrofuran; mineral oil at 0 - 20℃; for 24h; Inert atmosphere;
Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: benzaldehyde In tetrahydrofuran; mineral oil for 16h;

  • 94
  • [ 17145-91-4 ]
  • [ 613-69-4 ]
  • ethyl (E)-2-(2-ethoxybenzylidene)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: 2-ethoxylbenzaldehyde In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; Inert atmosphere; 5.1 Step 1: To a stirred suspension of NaH (60% dispersion in mineral oil) (226 mg, 5.66 mmol) in THF (7 mL) was added ethyl 2-(diethoxyphosphoryl)butanoate (1 .18 mL, 4.95 mmol) in THF (3 mL) drop wise at 0 °C under nitrogen atmosphere. After completion of the addition, the reaction mixture was stirred at RT for 1 h. Again, the mixture was cooled to 0 °C and 2- ethoxybenzaldehyde (500 mg, 3.33 mmol) was added and the mixture was stirred at RT for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with cold water (20 mL) and extracted with EtOAc (3 x 20 mL). Separated organic layer was washed with saturated NaHC03solution (30 mL) and brine (30 mL). Organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Obtained crude material was purified through silica gel column chromatography using 4% EtOAc/ hexane to afford ethyl (E)-2-(2-ethoxybenzylidene)butanoate (500 mg, 60%) as colourless syrup.ethyl (E)-2-(2-ethoxybenzylidene)butanoate:1H NMR (400MHz, CDCI3): δ 7.28-7.26 (m, 1 H), 7.23-7.14 (m, 1 H), 6.97-6.78 (m, 3H), 4.28 (q, J = 7.1 Hz, 2H), 4.1 1 -4.00 (m, 2H), 2.52-2.44 (m, 2H), 1.45-1.40 (m, 3H), 1.35 (t, J=7.2 Hz, 3H), 1 .18-1 .13 (m, 3H); LC-MS (ESI): 70.79%; m/z 249.0 [M + H]+at RT 3.09 min; (column; column; Ascentis Express C-18 (50 3.0mm, 2.7μη); 0.025% Aq TFA + 5% ACN: ACN + 5% 0.025% Aq TFA; 1.2 mL/min).
  • 95
  • [ 17145-91-4 ]
  • C17H16FN3O [ No CAS ]
  • C23H28FN3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: triethyl 2-ethylphosphonoacetate; C17H16FN3O With sodium hydride In tetrahydrofuran at 20℃; Stage #2: With palladium 10% on activated carbon; hydrogen In ethanol at 20℃;
  • 96
  • [ 17145-91-4 ]
  • 5-((4-chloro-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-fluorobenzyl)oxy)benzaldehyde [ No CAS ]
  • ethyl 2-(5-((4-chloro-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-fluorobenzyl)oxy)benzylidene)butanoate [ No CAS ]
  • ethyl (E)-2-(5-((4-chloro-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-fluorobenzyl)oxy)benzylidene)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
58 % de Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 5-((4-chloro-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-fluorobenzyl)oxy)benzaldehyde In tetrahydrofuran at 0℃; for 3h; Inert atmosphere; Overall yield = 83 percent; Overall yield = 273 mg; General Procedure 3: Wittig-Horner Reaction General procedure: Sodium hydride (1.3 eq.) was suspended in THF under argon atmosphere. After 15 min of stirring the mixture was cooled to 0°C and the corresponding phosphonoate (1.3 eq.) in THF (10 mL) was added within a few minutes via septum. After 30 min, the aldehyde (1.0 eq.) was added portionwise and the mixture was stirred at 0 °C until completion of the reaction (3h). The solvent was evaporated and the product was purified by flash chromatography. Compounds were generally obtained as an E/Z mixture. NMR data only given for E isomer.
  • 97
  • [ 17145-91-4 ]
  • ethyl 6-formyl-5-nitropyridine-3-carboxylate [ No CAS ]
  • ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]-5-nitropyridine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 40℃; for 0.416667h; Stage #2: ethyl 6-formyl-5-nitropyridine-3-carboxylate In tetrahydrofuran; mineral oil at -78℃; 3 Intermediate 9: ethyl 6-ffE)-2-ethoxycarbonylbut-1-enyll-5-nitro-Dyridine-3-carboxylate ( mixture of E/Z isomers ) To a stirred solution of sodium hydride (9.63 g, 240.89 mmol) (60% in mineral oil) in anhydrous THF (100 mL) was added ethyl 2-(diethoxyphosphoryl)butanoate (60.8 g, 240.89 mmol) dropwise with an addition funnel at 0°C to give a grey colored mixture. The resulting mixture was stirred at 0°C for 10 min and warmed to room temperature over 10 minutes and stirred at 40°C for 5 minutes. The reaction mixture was cooled to -78°C and to this cooled reaction mixture was then slowly added solution of ethyl 6-formyl-5-nitro-pyridine-3-carboxylate (Intermediate 8, 22.5 g, 100.37 mmol) in 100 ml THF. The mixture was quenched with sat.NH4CI solution, extracted with ethyl acetate. The combined the organic layers were dried over sodium Na2SC>4, filtered and concentrated to give crude product the resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in hexanes. Product fractions were concentrated under reduced pressure to afford ethyl 6-[(E)-2-ethoxycarbonylbut- 1 -enyl]-5-nitro-pyridine-3-carboxylate (Intermediate 9, 24.30 g, 75 %) as a yellow oil (1 :1 and mixture of E/Z isomer). 1 H NMR (500 MHz, CHLOROFORM-d) 1.13 (3H, t), 1 .18 (3H, t), 1 .23 (3H, t), 1 .37 (3H, t), 1.45 (6H, q), 2.57 (2H, qd), 2.66 (2H, q), 4.1 1 - 4.24 (2H, m), 4.32 (2H, q), 4.45 - 4.56 (4H, m), 7.08 (1 H, s), 7.85 (1 H, s), 8.86 (2H, dd), 9.26 (1 H, d), 9.43 (1 H, d); m/z (ES+) [M]+ = 322
75% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 40℃; for 0.416667h; Stage #2: ethyl 6-formyl-5-nitropyridine-3-carboxylate In tetrahydrofuran; mineral oil at -78℃; 1 Intermediate 3: ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]-5-nitro-pyridine-3-carboxylate (mixtureof E/Z isomers) To a stirred solution of sodium hydride (9.63 g, 240.89 mmol) (60% in mineral oil) in anhydrous THF (100 mL) was added ethyl 2-(diethoxyphosphoryl)butanoate (60.8 g, 240.89 mmol) dropwise with an addition funnel at 0°C to give a grey colored mixture. The resulting mixture was stirred at 0°C for 10 min and warmed to room temperature over 10 minutes and stirred at 40°C for 5 minutes. The reaction mixture was cooled to -78°C and to this cooled reaction mixture was then slowly added solution of ethyl 6-formyl-5-nitro-pyridine-3-carboxylate (Intermediate 2, 22.5 g, 100.37 mmol) in 100 mL THF. The mixture was quenched with sat. NH4CI solution, extracted with ethyl acetate. The combined the organic layers were dried over sodium Na2SO4, filtered and concentrated to give crude product, the resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in hexanes. Product fractions were concentrated under reduced pressure to afford ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]-5-nitro- pyridine-3-carboxylate (Intermediate 3, 24.30 g, 75 %) as a yellow oil (1 :1 and mixture of E/Z isomer). 1 H NMR (500 MHz, CHLOROFORM-d) 1.13 (3H, t), 1.18 (3H, t), 1.23 (3H, t), 1.37 (3H, t), 1 .45 (6H, q), 2.57 (2H, qd), 2.66 (2H, q), 4.11 - 4.24 (2H, m), 4.32 (2H, q), 4.45 - 4.56 (4H, m), 7.08 (1 H, s), 7.85 (1 H, s), 8.86 (2H, dd), 9.26 (1 H, d), 9.43 (1 H, d); m/z (ES+) [M]+ = 322
75% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 40℃; for 0.416667h; Stage #2: ethyl 6-formyl-5-nitropyridine-3-carboxylate In tetrahydrofuran; mineral oil at -78℃; 1 Intermediate 3: ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]-5-nitro-pyridine-3-carboxylate (mixtureof E/Z isomers) To a stirred solution of sodium hydride (9.63 g, 240.89 mmol) (60% in mineral oil) in anhydrous THF (100 mL) was added ethyl 2-(diethoxyphosphoryl)butanoate (60.8 g, 240.89 mmol) dropwise with an addition funnel at 0°C to give a grey colored mixture. The resulting mixture was stirred at 0°C for 10 min and warmed to room temperature over 10 minutes and stirred at 40°C for 5 minutes. The reaction mixture was cooled to -78°C and to this cooled reaction mixture was then slowly added solution of ethyl 6-formyl-5-nitro-pyridine-3-carboxylate (Intermediate 2, 22.5 g, 100.37 mmol) in 100 mL THF. The mixture was quenched with sat. NH4CI solution, extracted with ethyl acetate. The combined the organic layers were dried over sodium Na2SO4, filtered and concentrated to give crude product, the resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in hexanes. Product fractions were concentrated under reduced pressure to afford ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]-5-nitro- pyridine-3-carboxylate (Intermediate 3, 24.30 g, 75 %) as a yellow oil (1 :1 and mixture of E/Z isomer). 1 H NMR (500 MHz, CHLOROFORM-d) 1.13 (3H, t), 1.18 (3H, t), 1.23 (3H, t), 1.37 (3H, t), 1 .45 (6H, q), 2.57 (2H, qd), 2.66 (2H, q), 4.11 - 4.24 (2H, m), 4.32 (2H, q), 4.45 - 4.56 (4H, m), 7.08 (1 H, s), 7.85 (1 H, s), 8.86 (2H, dd), 9.26 (1 H, d), 9.43 (1 H, d); m/z (ES+) [M]+ = 322
75% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 40℃; for 0.416667h; Stage #2: ethyl 6-formyl-5-nitropyridine-3-carboxylate In tetrahydrofuran; mineral oil at -78℃; Intermediate 9: ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]- 5-nitro-pyridine-3-carboxylate (mixture of E/Z isomers) To a stirred solution of sodium hydride (9.63 g, 240.89 mmol) (60% in mineral oil) in anhydrous THF (100 mL) was added ethyl 2- (diethoxyphosphoryl)butanoate (60.8 g, 240.89 mmol) dropwise with an addition funnel at 0°C to give a grey colored mixture. The resulting mixture was stirred at 0°C for 10 min and warmed to room temperature over 10 minutes and stirred at 40°C for 5 minutes. The reaction mixture was cooled to -78°C and to this cooled reaction mixture was then slowly added solution of ethyl 6-formyl-5-nitro-pyridine-3-carboxylate (Intermediate 8, 22.5 g, 100.37 mmol) in 100 ml THF. The mixture was quenched with sat.NH4Cl solution, extracted with ethyl acetate. The combined the organic layers were dried over sodium Na2SO4, filtered and concentrated to give crude product, the resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in hexanes. Product fractions were concentrated under reduced pressure to afford ethyl 6- [(E)-2-ethoxycarbonylbut-1-enyl]-5-nitro-pyridine-3-carboxylate (Intermediate 9, 24.30 g, 75 %) as a yellow oil (1:1 and mixture of E/Z isomer). 1H NMR (500 MHz, CHLOROFORM-d) 1.13 (3H, t), 1.18 (3H, t), 1.23 (3H, t), 1.37 (3H, t), 1.45 (6H, q), 2.57 (2H, qd), 2.66 (2H, q), 4.11 - 4.24 (2H, m), 4.32 (2H, q), 4.45 - 4.56 (4H, m), 7.08 (1H, s), 7.85 (1H, s), 8.86 (2H, dd), 9.26 (1H, d), 9.43 (1H, d); m/z (ES+) [M]+ = 322.
75% Stage #1: ethyl 2-(diethoxyphosphoryl)butanoate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 40℃; for 0.416667h; Stage #2: ethyl 6-formyl-5-nitropyridine-3-carboxylate In tetrahydrofuran; mineral oil at -78℃; Intermediate 9: ethyl 6-[(E)-2-ethoxycarbonylbut-1-enyl]- 5-nitro-pyridine-3-carboxylate (mixture of E/Z isomers) To a stirred solution of sodium hydride (9.63 g, 240.89 mmol) (60% in mineral oil) in anhydrous THF (100 mL) was added ethyl 2- (diethoxyphosphoryl)butanoate (60.8 g, 240.89 mmol) dropwise with an addition funnel at 0°C to give a grey colored mixture. The resulting mixture was stirred at 0°C for 10 min and warmed to room temperature over 10 minutes and stirred at 40°C for 5 minutes. The reaction mixture was cooled to -78°C and to this cooled reaction mixture was then slowly added solution of ethyl 6-formyl-5-nitro-pyridine-3-carboxylate (Intermediate 8, 22.5 g, 100.37 mmol) in 100 ml THF. The mixture was quenched with sat.NH4Cl solution, extracted with ethyl acetate. The combined the organic layers were dried over sodium Na2SO4, filtered and concentrated to give crude product, the resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in hexanes. Product fractions were concentrated under reduced pressure to afford ethyl 6- [(E)-2-ethoxycarbonylbut-1-enyl]-5-nitro-pyridine-3-carboxylate (Intermediate 9, 24.30 g, 75 %) as a yellow oil (1:1 and mixture of E/Z isomer). 1H NMR (500 MHz, CHLOROFORM-d) 1.13 (3H, t), 1.18 (3H, t), 1.23 (3H, t), 1.37 (3H, t), 1.45 (6H, q), 2.57 (2H, qd), 2.66 (2H, q), 4.11 - 4.24 (2H, m), 4.32 (2H, q), 4.45 - 4.56 (4H, m), 7.08 (1H, s), 7.85 (1H, s), 8.86 (2H, dd), 9.26 (1H, d), 9.43 (1H, d); m/z (ES+) [M]+ = 322.

  • 98
  • [ 1117-52-8 ]
  • [ 17145-91-4 ]
  • ethyl (6E,10E)-2-ethyl-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% Stage #1: 6,10,14-trimethyl-5,9,13-pentadecatriene-2-on; triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0 - 45℃; for 170h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In ethanol at 0℃; for 1h; Inert atmosphere; 14 Ethyl (2E,6E,10E)-2-ethyl-3,7,ll,15-tetramethylhexadeca-2,6,10,14-tetraenoate and ethyl (2Z,6E,10E)-2-ethyl-3,7,ll,15-tetramethylhexadeca-2,6,10,14-tetraenoate. A 25.0 mL 14/20 round bottom flask was charged with sodium hydride (0.839 g, 34.9 mmol), tetrahydrofuran (20.0 mL) was, under argon atmosphere at 0 °C, charged with triethyl-2- phosphonobutyrate (4.89 g, 19.4 mmol) dissolved in tetrahydrofuran (2.00 mL). Once gas evolution ceased famesyl acetone (1.05 g, 4.00 mmol) was added as a solution in tetrahydrofuran (2.00 mL). The reaction mixture was heated to 45 °C for 170 hours, cooled to 0 °C, quenched with water and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a mixture of ethyl (2E,6E,10E)-2-ethyl-3, 7,11, 15-tetramethylhexadeca-2, 6, 10,14- tetraenoate and ethyl (2Z,6E,10E)-2-ethyl-3, 7,11, 15-tetramethylhexadeca-2, 6, 10,14- tetraenoate, in a 1 to 1 mixture, and unreacted farnesyl acetone. The crude mixture was dissolved in ethanol (20.0 mL), cooled to 0 °C and unreacted farnesyl acetone was reduced with sodium borohydride (0.230 g, 6.20 mmol) to ease purification. The reaction mixture was stirred for 1 hour, allowed to warm to room temperature, cooled to 0 °C and quenched with 1.00 N hydrochloric acid. The reaction mixture was concentrated in vacuo, partitioned between ethyl acetate and water, the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The mixture was purified by silica gel chromatography (0 - 10 % ethyl acetate in hexanes) to yield a mixture of cis and trans isomers, ethyl (2E,6E,10E)-2-ethyl-3,7,ll,15-tetramethylhexadeca-2,6,10,14-tetraenoate and ethyl (2Z,6E,10E)-2-ethyl-3,7,ll,15-tetramethylhexadeca-2,6,10,14-tetraenoate (0.770 g, 31 %). NMR (500 MHz, CDCE) d 5.12 (dt, J = 13.8, 6.0 Hz, 3H), 4.24 - 4.07 (m, 2H), 2.35 - 2.21 (m, 3H), 2.19 - 1.88 (m, 12H), 1.78 (s, 1H), 1.68 (s, 5H), 1.60 (d, 7= 5.0 Hz, 8H), 1.29 (td, J= 7.1, 5.4 Hz, 3H), 1.04 - 0.80 (m, 3H).
  • 99
  • [ 17145-91-4 ]
  • 4-(2-amino-6-(trifluoromethyl)pyridin-3-yl)cyclohexan-1-one [ No CAS ]
  • ethyl (RS)-2-(4-(2-amino-6-(trifluoromethyl)pyridin-3-yl)cyclohexylidene)butyrate [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% Stage #1: triethyl 2-ethylphosphonoacetate In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: 4-(2-amino-6-(trifluoromethyl)pyridin-3-yl)cyclohexan-1-one In tetrahydrofuran; mineral oil at 20℃; for 3h; Inert atmosphere; 2.D (D) Ethyl (RS) -2- (4- (2-amino-6- (trifluoromethyl) pyridin-3-yl) cyclohexylidene) butyrate 60%NaH (366 mg, 9.16 mmol) and dry THF (40 mL) were added to a reaction flask under nitrogen protection, cooled to 0, and added with ethyl 2-(ethoxyphosphono) butyrate (2.31 g, 9.16 mmol) dropwise. The reactants were stirred at 0 for 20 minutes and at room temperature for 40 minutes. 4- (2-amino-6- (trifluoromethyl) pyridin-3-yl) cyclohexan-1-one (1.82 g, 7.05 mmol) was dissolved in dry THF (10 mL) , added dropwise to the above reaction mixture, and stirred at room temperature for 3 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate. The organic phase was concentrated, and purified by flash column chromatography (petroleum ether/ethyl acetate = 100: 0 to 0: 100, gradient elution) to obtain a white solid product (1.82 g, yield 72%) . 357.0 [M+H]+
  • 101
  • [ 40320-60-3 ]
  • [ 17145-91-4 ]
  • ethyl 2-(1-benzhydrylazetidin-3-ylidene)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77.37% Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: N-benzhydryl 3-azetidinone In tetrahydrofuran at 20 - 25℃; for 3h; Inert atmosphere;
Recommend Products
Same Skeleton Products
Historical Records