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CAS No. : | 1552-92-7 | MDL No. : | MFCD00017627 |
Formula : | C10H16O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MCWDXHYYYNGYGK-UHFFFAOYSA-N |
M.W : | 168.23 | Pubchem ID : | 73776 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium hydroxide; In methanol; water; at 20℃; for 16h; | Triethyl phosphonoacetate (232.0 g, 1.0 equiv) was dissolved in abs. tetrahydrofuran (200 mL) and added to a suspension, cooled down to 0 C., of sodium hydride (42.0 g, 1.02 equiv, 60% dispersion) in abs. tetrahydrofuran (200 mL). The resulting reaction mixture was stirred at a temperature of 0 C. for 10 minutes and then admixed with a solution of cyclohexanone (100.0 g, 1.0 equiv) in abs. tetrahydrofuran (300 mL), and the mixture was stirred at room temperature for a further 4 h. After the cautious addition of water, the reaction mixture was concentrated under reduced pressure and admixed with dichloromethane. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), ethyl cyclohexylideneacetate (105.0 g) was isolated. Ethyl cyclopentylideneacetate (105.0 g, 1.0 equiv) was dissolved in methanol and admixed with a 1 M solution of KOH in aq. methanol (1000 mL). The resulting reaction mixture was stirred at room temperature for 16 h, then neutralized cautiously with dil. HCl, admixed with water, concentrated under reduced pressure and then admixed with dichloromethane. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), cyclohexylideneacetic acid (70.0 g, 80% of theory) was isolated. Aniline (41.5 g, 1.0 eq.) was dissolved in dichloromethane (500 mL) and cooled down to a temperature of 0 C., and diisopropylethylamine (354 mL, 4.0 equiv.), cyclohexylideneacetic acid (70.0 g, 1.0 equiv.) and N,N,N′,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (180 g, 1.1 equiv.) were added. The resulting reaction mixture was stirred at room temperature for 3 h, and water and dichloromethane were then added. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 2-cyclohexylidene-N-phenylacetamide (80.0 g, 74% of theory) was isolated. In the next step, aluminum trichloride (93.2 g, 3.0 equiv.) was initially charged in abs. dichloromethane (400 mL) under argon in a baked-out round-bottom flask and then, while cooling with ice, a solution of 2-cyclohexylidene-N-phenylacetamide (50.0 g, 1.0 equiv.) in abs. dichloromethane (100 mL) was added. The resulting reaction mixture was stirred at room temperature for a further 4 h and then added cautiously to ice-water. After adding aqueous HCl and dichloromethane, the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated cautiously under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (12.0 g, 24% of theory) was isolated as a colorless solid. 1′H-Spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (12.0 g, 55.80 mmol, 1 eq.) was added to conc. acetic acid (100 mL) and then cautiously admixed with fuming nitric acid (20 mL). The resulting reaction mixture was stirred at 70 C. for 1 h and, after cooling to room temperature, cautiously diluted with ice-water. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 6′-nitro-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (2500 mg, 17% of theory) was isolated as a colorless solid. 6′-Nitro-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (1000 mg, 3.84 mmol, 1.0 equiv.) was dissolved under argon in a mixture of abs. dioxane and N,N-dimethylformamide (5:1, 12 mL) and admixed with fine cesium carbonate powder (3800 mg, 3.0 eq.). After stirring at room temperature for 5 min, cyclopropylmethyl bromide (1400 mg, 2.0 equiv.) and potassium iodide (64 mg, 0.1 equiv.) were added at room temperature. The resulting reaction mixture was stirred at 150 C. under microwave conditions for 1 h and, after cooling to room temperature, water and ethyl acetate were added. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1-(cyclopropylmethyl)-6′-nitro-1′H-spiro[cyclopentyl-1,4′-quinolin]-2′(3′H)-one (700 mg, 58% of the... |
72% | With water; potassium hydroxide; In methanol; at 27℃; for 48h; | To a solution of KOH (0.561g. 10 mmol) in H20 (7 mL) and MeOH (3 mL) was added ethyl 2-cyclohexylideneacetate 72 (1.0 g, 5.94 mmol) and stirred for two days at room temperature, reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3x10 mL), aqueous layer was acidified with iN HCI and extracted with ethyl acetate (2x 20 mE), organic layer was washed with water, dried over Na2SO4 and concentrated to obtain pure compound 2-cyclohexylideneacetic acid precursor-42 as white solid (0.6 g, 72% yield). ‘HNMR (400 MHz, CDC13): ö 11.84 (s, 1H), 5.52 (s, 111), 2.74-2.72 (m, 211), 2.14 (t, 2H), 1.53-1.52 (m, 6H). MS: 141.2 (M+H). |
300 mg | With lithium hydroxide monohydrate; water; In tetrahydrofuran; methanol; at 20℃; for 1h; | To a stirred solution of ethyl 2-cyclohexylideneacetate (1 g) in THF/H2O/MeOH (4 ml/2 ml/2 ml) was added LiOH.H2O (536 mg) at rt and the resulted mixture was stirred for 1 h at this temperature. The mixture was then acidified with 1N HCl. The solution was filtered and dried in vacuo to give 300 mg of the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil for 1h; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil for 18h; | |
98% | With sodium hydride In tetrahydrofuran for 8h; | |
97% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With 15-crown-5; sodium hydride In tetrahydrofuran; mineral oil at 0℃; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil at -40 - 20℃; | 1 Conjugated Ester 45 A dry reaction flask equipped with a stir bar, N2 inlet was charged with NaH (60% dispersed in oil; 4.62 g, 130 mmol) followed by a careful addition of dry THF (200 mL) and 15-crown-5 (0.2 g, catalyst). The reaction flask was cooled to 0° C. and to it was added phosphonoacetoacetate 6 (27.75 mL, 140 mmol) drop wise over 30-45 min. [CAUTION. Faster addition rate of phosphonoacetate can generate exotherm]. At the end of addition of phosphonoacetate, the heterogeneous reaction mixture starts turning into homogeneous or clear solution. After a complete addition, the reaction became clear solution and stir at the same temperature for 10-15 min. The clear solution was then cooled to -35 to -40° C. and to it was added cyclohexanone 44 (10.34 g, 100 mmol) drop wise over ˜30 min and then the resulting reaction was allowed to come to room temperature and stirred for 2-3 days. After quenching the reaction with water (200 mL) carefully, the THF layer was separated; the aqueous layer was extracted with n-hexanes (3*200 mL) and combined with THF layer. The combined organic phases were dried over Na2SO4 and solvent was removed under a reduced pressure to afford an oily material, which the desired product 45 was purified by fractional distillation under a reduced pressure; 60-64° C./1 mm of Hg; Yield: 16.25 g (97%); TLC Rf: 0.15 (5% EtOAc/n-hexanes); LCMS: MS (m/z): 169.20 (MH+). |
96% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; | |
96% | With sodium hydride In tetrahydrofuran; kerosene at 60℃; for 22h; Heating; | |
95% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran at 0 - 20℃; for 18h; | |
94% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; for 8h; | |
94% | With sodium hydride In tetrahydrofuran at 20℃; for 8h; | |
94% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With 1,8-diazabicyclo[5.4.0]undec-7-ene; sodium iodide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran Inert atmosphere; | |
93% | With sodium hydride In tetrahydrofuran at 0 - 20℃; for 8h; | 2-Cyclohexylideneethan-1-ol NaH in oil (132 mg, 5.5 mmol, 1.1 equiv) was washed by hexane, and THF was added (5 mL)at 0 °C. To a mixture was added triethyl phosphonoacetate (1.0 mL, 5 mmol, 1 equiv) andcyclohexanone in THF (5 mL). The mixture was stirred at 0 °C to rt for 8 h. The reactionmixture was quenched with NH4Cl aq. (5 mL) and extracted with Et2O. The organic layer wasdried over Na2SO4, and concentrated under reduced pressure to give ethyl 2-cyclohexylideneacetate as a colorless oil (93% yield, 783.8 mg, 4.7 mmol). This product wasused for next reaction without further purification. |
92% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran at 0 - 25℃; for 14h; Inert atmosphere; | |
92% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran at 0 - 20℃; for 14h; Inert atmosphere; | |
90% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With n-butyllithium In hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In hexane at -50 - 20℃; for 2.5h; Inert atmosphere; | To a THF (100 mL) solution of ethyl 2-(diethylphosphoryl)acetate (8.80 g, 39.1 mmol) was slowly added n-BuLi (1.6 M hexanesolution, 32.0 mL, 51.2 mmol) at78 °C under argon atmosphere and stirred for 30 min. Cyclohexanone (8.0 mL, 77.2 mmol) wasadded at50 °C and stirred for 30 min, then stirred at roomtemperature for 2 h. Sat. NH4Cl aq and Et2O were added andshaken. The organic layer was dried over Na2SO4,filtered, andconcentrated in vacuo. Distillation under reduced pressure (bp 78-81 °C/3 mmHg) gave ethyl cyclohexylideneacetate (5.91 g,35.2 mmol, 90% yield). Colorless oil; 1H NMR (CDCl3, 300 MHz) d1.28 (t, J = 7.2 Hz, 3H), 1.60-1.65 (m, 6H), 2.18 (m, 2H), 2.81 (m, 2H),4.14 (q, J = 7.1 Hz, 2H), 5.59 (s, 1H) ppm. |
89% | With 2,8,9-tris(2-methylpropyl)-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane In tetrahydrofuran at 20℃; for 8h; Inert atmosphere; | |
88% | With potassium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene for 48h; Inert atmosphere; neat (no solvent); | |
88% | With sodium hydride In tetrahydrofuran at 20℃; | |
87% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; for 8h; Inert atmosphere; | |
86% | With potassium <i>tert</i>-butylate In benzene at 20℃; for 10 - 12h; | |
81% | With potassium In toluene for 2h; Ambient temperature; | |
81% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil for 8h; | To a solution of ethyl 2-(diethoxyphosphoryl)acetate (1.09 mL, 5.5 mmol) in THF (10 mL) at 0 °C was added NaH (240 mg, 60 % in mineral oil). After 30 min at at 0 °C, cyclohexanone (518 mg, 5.0 mmol) was added dropwise. After 8 h, the mixture was quenched with saturated aq. NH4Cl (10 mL), extracted with ether (10 mL x 3). The combined organics were dried (MgSO4), filtered and the residue was purified by flash chromatography to give 681.6 mg (81 %) of a,b-unsaturated ester. |
80% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran Stage #2: cyclohexanone In tetrahydrofuran Further stages.; | |
75% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In diethyl ether at -5℃; for 0.0833333h; Stage #2: cyclohexanone With Wadsworth-Horner-Emmons reagent In diethyl ether for 4h; | |
71% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran at 25℃; for 2h; | |
62% | With triethylamine; magnesium bromide In tetrahydrofuran at 25℃; for 3h; other metal halides, other solvents, variety of aldehydes and ketones other time; | |
62% | With triethylamine; magnesium bromide In tetrahydrofuran at 25℃; for 3h; | |
56% | With potassium carbonate In water at 100℃; for 0.166667h; | |
50% | In acetonitrile Ambient temperature; electrolysis (Pt cathode, (C2H5)4NBr); | |
43% | With N,N,N',N'-tetramethylguanidine at 20℃; for 75h; Inert atmosphere; Neat (no solvent); stereoselective reaction; | |
43% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran | 1.1 Ethyl 2-diethoxyphosphorylacetate (235.0 g, 1.0 mol) was dissolved in THF (1500 ml) and cooled at 0°C. NaH (50.0 g, 1.2 mol) was added in portions and the solution was stirred at this temperature for 0.5 h. Then a solution of cyclohexanone (98.0 g, 1 .0 mol) in THF (200 ml) was added dropwise and the solution was stirred overnight. NH4CI aq. was added, extracted with MTBE (1000 ml_x2), washed with brine, dried over Na2S04 and concentrated, then purified by chromatogram on silica gel (PE: EA = 1000:1 - 100: 1 ) to afford ethyl 2-cyclohexylideneacetate (70.0 g, 43 %). 1H NMR: CDCIs 400MHz: 5.56 (m, 1 H), 4.15 (q, 2H J= 1 1 Hz), 2.95 (s, 1 H), 2.02 (m, 3H), 1 .48-1 .55 (m, 5H), 1.28 (t, 3H J= 10 Hz), 0.87 (m, 3H). |
33% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In diethyl ether at -5℃; for 0.25h; Stage #2: cyclohexanone In diethyl ether at -5 - 27℃; for 5h; | Synthesis of ethyl 2-cyclohexylideneacetate (72) To a stirred suspension of 60% NaH (0.83g, 20.75 mmol) in ether (60 mL), at-5°C was drop wise added ethyl 2-(diethoxyphosphoryl)acetate (4.1 mL, 20.66 mmol) and stirred for 15 mm (until H2 evolution stopped). A solution of cyclohexanone 71(2.09 mL, 20.2 mmol) in 10 mL di-ethylether was added slowly at -5°C, and allowed to stir at room temperature for about 5h, reaction mixture was quenched with 50 mE ice-water, ether layer was separated, and aqueous layer was extracted with ethyl acetate, combined organic extracts were dried over Na2SO4 and concentrated to obtain crude compound. The crude was further purified by combiflash using 0-40% ethyl acetate in hexane to obtain ethyl 2-cyclohexylideneacetate 72 as a colorless liquid (2.6 g, 33% yield). ‘HNMR (400 MHz, CDC13): ö 5.59 (s, 1H), 4.13 (q, 211), 2.82 (t, 2H), 2.18 (t, 2H), 1.67-1.57 (m, 6H), 1.26 (t, 3H). |
With sodium hydride; mineral oil; benzene | ||
With tetraethylammonium bromide 1.) MeCN, r.t., electrolysis; 2.) 1 h, boiling; Yield given. Multistep reaction; | ||
With sodium hydride In N,N-dimethyl-formamide 1) 20 deg C, 1 h, 2) 90 deg C to 100 deg C, 8 h; Yield given; | ||
79 % Chromat. | With aluminum oxide; potassium fluoride at 20℃; for 18h; | |
With sodium hydride 1.)benzene, 0 deg C, 2 h, 2.) benzene, 0 deg C, 40 min, r.t., 3 h, 60-65 deg C, 15 min,; Yield given. Multistep reaction; | ||
With sodium hydride | ||
With sodium hydride In tetrahydrofuran for 16h; | ||
With sodium hydride In tetrahydrofuran | ||
With sodium hydride 1.) DME, RT, 1 h, 2.) DME, RT, 30 min; Multistep reaction; | ||
With sodium hydride 1.) benzene, RT, 1 h, 2.) benzene, 65 deg C, 30 min; Yield given. Multistep reaction; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 20℃; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0 - 25℃; for 1h; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; for 2h; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran Stage #2: cyclohexanone In tetrahydrofuran at 20℃; | ||
With sodium hydride In tetrahydrofuran at 20℃; for 1h; | Synthesis of Ethyl Cyclohexylideneacetate To slurry of triethyl phosphonoacetate (5.05, 22.3mmole) in tetrahydrofuran (5ml) at 200C was added sodium hydride (0.892g, 22.3mmole) portionwise with constant stirring followed by the addition of cyclohexanone (1.87ml, 22.3mmole) in tetrahydrofuran (2ml) dropwise. The reaction mixture was stirred for 1 hour. The mixture was diluted with EPO water and extracted with ethyl acetate, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography to furnish the title compound. Yield: 2.5 gm | |
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil at 20℃; for 8h; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; | General Procedure for Synthesis of Esters General procedure: A two-necked round bottom flask was dried using heat gun under reduced pressure and filled with argon. To this flask was added NaH (500 mg, 60% dispersion in mineral oil, 12.5 mmol, 1.25 eq) and the flask was evacuated and refilled with argon (×3). To the flask was added THF (25 mL) and the suspension was cooled to 0° C, then triethyl phosphonoacetate (2.5 mL, 12.5 mmol, 1.25 eq) was carefully added (CAUTION: evolution of H2 gas). The resultant mixture was stirred for 30 min at 0° C and then 4-chlorobenzaldehyde (1.41 g, 10 mmol, 1.0 eq) was added at the same temperature. The reaction was stirred for additional 1 h at 0° C and then quenched with saturated aq. NaHCO3 followed by extraction with Et2O (×3). Combined organic layer was washed with brine (×1), dried over Na2SO4 and filtered. Volatiles were removed under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: hexane/EtOAc 10:1) to afford the title compound as a colorless oil in 78% yield (1.63 g). | |
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Cooling with ice; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil at 20℃; for 4h; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil Inert atmosphere; Reflux; | ||
With sodium hydride In tetrahydrofuran at 20℃; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil for 6h; | ||
105 g | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.166667h; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; for 4h; | 13-178 Triethyl phosphonoacetate (232.0 g, 1.0 equiv) was dissolved in abs. tetrahydrofuran (200 mL) and added to a suspension, cooled down to 0° C., of sodium hydride (42.0 g, 1.02 equiv, 60% dispersion) in abs. tetrahydrofuran (200 mL). The resulting reaction mixture was stirred at a temperature of 0° C. for 10 minutes and then admixed with a solution of cyclohexanone (100.0 g, 1.0 equiv) in abs. tetrahydrofuran (300 mL), and the mixture was stirred at room temperature for a further 4 h. After the cautious addition of water, the reaction mixture was concentrated under reduced pressure and admixed with dichloromethane. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), ethyl cyclohexylideneacetate (105.0 g) was isolated. Ethyl cyclopentylideneacetate (105.0 g, 1.0 equiv) was dissolved in methanol and admixed with a 1 M solution of KOH in aq. methanol (1000 mL). The resulting reaction mixture was stirred at room temperature for 16 h, then neutralized cautiously with dil. HCl, admixed with water, concentrated under reduced pressure and then admixed with dichloromethane. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), cyclohexylideneacetic acid (70.0 g, 80% of theory) was isolated. Aniline (41.5 g, 1.0 eq.) was dissolved in dichloromethane (500 mL) and cooled down to a temperature of 0° C., and diisopropylethylamine (354 mL, 4.0 equiv.), cyclohexylideneacetic acid (70.0 g, 1.0 equiv.) and N,N,N′,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (180 g, 1.1 equiv.) were added. The resulting reaction mixture was stirred at room temperature for 3 h, and water and dichloromethane were then added. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 2-cyclohexylidene-N-phenylacetamide (80.0 g, 74% of theory) was isolated. In the next step, aluminum trichloride (93.2 g, 3.0 equiv.) was initially charged in abs. dichloromethane (400 mL) under argon in a baked-out round-bottom flask and then, while cooling with ice, a solution of 2-cyclohexylidene-N-phenylacetamide (50.0 g, 1.0 equiv.) in abs. dichloromethane (100 mL) was added. The resulting reaction mixture was stirred at room temperature for a further 4 h and then added cautiously to ice-water. After adding aqueous HCl and dichloromethane, the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated cautiously under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (12.0 g, 24% of theory) was isolated as a colorless solid. 1′H-Spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (12.0 g, 55.80 mmol, 1 eq.) was added to conc. acetic acid (100 mL) and then cautiously admixed with fuming nitric acid (20 mL). The resulting reaction mixture was stirred at 70° C. for 1 h and, after cooling to room temperature, cautiously diluted with ice-water. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 6′-nitro-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (2500 mg, 17% of theory) was isolated as a colorless solid. 6′-Nitro-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (1000 mg, 3.84 mmol, 1.0 equiv.) was dissolved under argon in a mixture of abs. dioxane and N,N-dimethylformamide (5:1, 12 mL) and admixed with fine cesium carbonate powder (3800 mg, 3.0 eq.). After stirring at room temperature for 5 min, cyclopropylmethyl bromide (1400 mg, 2.0 equiv.) and potassium iodide (64 mg, 0.1 equiv.) were added at room temperature. The resulting reaction mixture was stirred at 150° C. under microwave conditions for 1 h and, after cooling to room temperature, water and ethyl acetate were added. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1-(cyclopropylmethyl)-6′-nitro-1′H-spiro[cyclopentyl-1,4′-quinolin]-2′(3′H)-one (700 mg, 58% of theory) was isolated as a colorless solid. In the next step, 1-(cyclopropylmethyl)-6′-nitro-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (900 mg, 1.0 equiv.) together with zinc powder (931 mg, 5.0 eq.) and ammonium chloride (759 mg, 5.0 eq.) were added to abs. methanol at a temperature of 0° C. and the mixture was stirred under argon at room temperature for 1 h. The reaction mixture was then poured onto ice-water and subsequently adjusted to pH 12 with 6 N NaOH. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 6′-amino-1-(cyclopropylmethyl)-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (750 mg, 92% of theory) was isolated as a colorless solid. 6′-Amino-1-(cyclopropylmethyl)-1′H-spiro[cyclohexyl-1,4′-quinolin]-2′(3′H)-one (70 mg, 1.0 equiv.) was dissolved together with 4-trifluoromethylbenzylsulfonyl chloride (70 mg, 1.1 equiv) in abs. dichloromethane (5 mL) under argon in a baked-out round-bottom flask under argon, then pyridine (0.1 mL, 5.0 equiv.) was added and the mixture was stirred at room temperature for 1 h. The reaction mixture was then concentrated under reduced pressure, the remaining residue was admixed with dil. HCl and dichloromethane, and the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), N-[1′-(cyclopropylmethyl)-2′-oxo-2′,3′-dihydro-1′H-spiro[cyclohexane-1,4′-quinolin]-6′-yl]-1-(4-trifluoromethylphenyl)methanesulfonamide (60 mg, 48% of theory) was isolated as a colorless solid. 1H-NMR (400 MHz, CDCl3 δ, ppm) 7.66 (d, 2H), 7.48 (d, 2H), 7.14-7.08 (m, 2H), 7.05 (m, 1H), 6.13 (s, 1H, NH), 4.39 (s, 2H), 3.39 (m, 2H), 2.67 (s, 2H), 1.78 (m, 1H), 1.71-1.54 (m, 8H), 1.29 (m, 1H), 1.11 (m, 1H), 0.50 (m, 2H), 0.43 (m, 2H). |
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; | 4.4.10. (E)-(4-Iodobut-2-en-2-yl)benzene (1j) General procedure: Neat triethyl phosphonoacetate (2.24 g, 10 mmol) was added to a suspension of NaH (60%, 400 mg, 10 mmol) in dry THF (50 mL). After 30 min, a solution of acetophenone (960 mg, 8 mmol) in dry THF (10 mL) was added, and the resulting mixture was stirred over night. The reaction was quenched by the addition of water (50 mL). The organic layer was separated, and the aqueous layer was extracted with Et2O (3 50 mL). The combined organic solutions were dried over anhydrous Na2SO4, concentrated and purified by column chromatography on silica gel (Hexane/EtOAc 10:1, v/v) to afford ethyl (E)-3-phenylbut-2-enoate (16a) as a colorless oil, 1.25 g, 82% yield. | |
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 23℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran at 23℃; Sealed tube; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil at 0 - 20℃; for 15h; Inert atmosphere; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil for 1h; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran; mineral oil at 0 - 20℃; | ||
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0 - 10℃; for 0.5h; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; | 107.1 Step 1 ethyl 2-cyclohexylideneacetate To a stirred solution of ethyl 2- (diethoxyphosphoryl) acetate (1.26 g, 5.61 mmol) in THF (10 ml) was added NaH (135 mg, 5.61 mmol) in portions at 0-10. The resulted mixture was stirred for 30 min at this temperature. Cyclohexanone (500 mg, 10 mmol) was added in portions. The mixture was then warmed to rt and stirred for 1-2 h. Then the mixture was poured into ice-water and extracted with EA. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give 1 g of the crude product. | |
105 g | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.166667h; Stage #2: cyclohexanone In tetrahydrofuran at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With chloro-trimethyl-silane; copper(I) (trimethylsilyl)acetylide In tetrahydrofuran; diethyl ether; hexane 1.) -78 deg C, 1 h; 2.) to r.t. within 4 h; | |
With copper(l) iodide; boron trifluoride diethyl etherate In diethyl ether; hexane | ||
With copper(l) iodide; boron trifluoride diethyl etherate 1.) ether, hexane, a) -30 deg C, 20 min, b) from -75 to 70 deg C, 2.) from -75 deg C to RT; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene for 0.5h; | |
96% | With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; Inert atmosphere; | 1 Allylic Alcohol 46 To a dry reaction flask was placed conjugated ester 45 (13.4 g, 80 mmol) and THF (160 mL). At 0° C., under a N2 atmosphere (with a vent) was added LAH (2M solution in THF, 40 mL, 80 mmol) drop wise with cautions over ˜40-60 min. The resulting reaction was then stirred for additional 2 h at 0° C., which was monitored by TLC. Once the reaction was completed, it was quenched with EtOAc (10 mL) followed by H2O (20 mL) very carefully, since it generated gaseous hydrogen. The resulting jelly obtained was diluted with EtOAc (100 mL), the solid mass was filtered through celite and the celite pad was washed with EtOAc (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4 and solvent was removed under a reduced pressure, and the resulting oily material was dried under high vacuum to afford 9.67 g (96%) of the desired alcohol 46. TLC Rf: 0.085 (10% EtOAc/n-hexanes); LCMS: MS (m/z): 109 (M- OH). |
94% | Stage #1: ethyl cyclohexylideneacetate With diisobutylaluminium hydride In tetrahydrofuran; toluene Inert atmosphere; Cooling with acetonitrile-dry ice; Stage #2: With rochelle salt; glycerol In tetrahydrofuran; toluene Saturated solution; |
92% | With lithium aluminium tetrahydride In diethyl ether at -78℃; for 2h; | |
92% | With lithium aluminium tetrahydride In diethyl ether at -70℃; for 2h; | |
92% | With lithium aluminium tetrahydride In diethyl ether at 0℃; for 2h; | |
90% | With diisobutylaluminium hydride In toluene at -78 - 25℃; for 3.25h; Inert atmosphere; | |
90% | With diisobutylaluminium hydride In dichloromethane at -78℃; for 3h; Inert atmosphere; | |
89% | With diisobutylaluminium hydride In tetrahydrofuran; toluene at -20℃; for 3h; | |
89% | With diisobutylaluminium hydride In tetrahydrofuran; toluene at -20℃; | |
88% | With lithium aluminium tetrahydride In diethyl ether | |
83% | With aluminium hydride In diethyl ether at 0℃; for 0.5h; | |
83% | With aluminium hydride In diethyl ether | |
83% | Stage #1: ethyl cyclohexylideneacetate With diisobutylaluminium hydride In toluene at -78 - 20℃; for 3h; Stage #2: With water; sodium hydroxide | |
81% | With diisobutylaluminium hydride In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere; | |
78% | With lithium aluminium tetrahydride In diethyl ether at 20℃; for 4h; | |
77% | With lithium aluminium tetrahydride In diethyl ether at -78 - 20℃; for 10h; | |
75% | With lithium aluminium tetrahydride In diethyl ether at 0℃; for 1h; | To a solution of lithium aluminum hydride (56.9 mg, 1.5 mmol) in ether (5 mL) at 0 °C, was added dropwise a,b-unsaturated ester (168.2 mg, 1.0 mmol) above. After 1 h, the mixture was quenched with a saturated solution of Rochelle’s salt and the aqueous layer was extracted with ether (10 mL x 3). The combined organic layers were dried (MgSO4), filtered and the residue was purified by flash chromatography to give 95.2 mg (75 %) of the corresponding allylic alcohol. |
71% | With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 2h; | 2-Cyclohexylideneethan-1-ol A solution of LiAlH4 (353.7 mg, 9.3 mmol, 2 equiv) in Et2O (5 mL) was added a solution ofreactant (783.8 mg, 4.7 mmol, 1 equiv) in Et2O (5 mL) at 0 °C. The mixture was stirred at 0 °Cto rt for 2 h. The reaction mixture was quenched with H2O and extracted with CH2Cl2.Purification was performed by silica gel column chromatography (Hex/EA = 9/1) to give 2-cyclohexylideneethan-1-ol as a colorless oil (71% yield, 418.0 mg, 3.3 mmol). 1H NMR (500MHz, CDCl3) δ 5.36 (t, J = 7.26 Hz, 1H), 4.14 (d, J = 7.26 Hz, 2H), 2.232.08 (m, 4H), 1.581.51 (m, 6H) ppm. |
70% | With sodium bis(2-methoxyethoxy)aluminium dihydride In diethyl ether; benzene 0 deg C, r.t., 6 h; | |
59% | With diisobutylaluminium hydride In diethyl ether; toluene at 20℃; for 20h; | |
43% | With lithium aluminium tetrahydride In tetrahydrofuran at -30 - 0℃; for 1h; | |
42% | With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78 - 20℃; for 1.5h; | To THF (100 mL) solution ofethyl cyclohexylideneacetate (4.20 g, 25.0 mmol) was slowly addediBu2AlH (1.0 M hexane solution, 100 mL, 100 mmol) at -78 °C,stirred for 30 min. Then the solution was stirred at roomtemperature for 1 h. After cooling to 0 °C, wet Na2SO4 was addedand stirred for 1 h. The precipitated colorless solid was collected washed with Et2O, and concentrated in vacuo. Distillation underreduced pressure (bp 88-90 °C/7 mmHg) gave (2-hydroxyethyli-dene) cyclohexane (1.33 g, 10.6 mmol, 42% yield). Colorless oil; 1HNMR (CDCl3, 300 MHz) δ 0.89-1.61 (m, 7H), 2.11-2.21 (m, 4H), 4.13(dd, J = 7.0 Hz, 0.4 Hz, 2H), 5.36 (m, 1H) ppm. |
37% | With lithium aluminium tetrahydride In diethyl ether at -78 - 20℃; Inert atmosphere; | |
(i) LiAlH4, Et2O, (ii) (hydrolysis); Multistep reaction; | ||
With lithium aluminium tetrahydride In diethyl ether Ambient temperature; | ||
With lithium aluminium tetrahydride | ||
With lithium aluminium tetrahydride In diethyl ether | ||
With lithium aluminium tetrahydride In diethyl ether at -70℃; for 2h; Yield given; | ||
With lithium aluminium tetrahydride In diethyl ether at -50℃; for 2h; | ||
With lithium aluminium tetrahydride In diethyl ether | ||
With diisobutylaluminium hydride In dichloromethane at -78℃; | ||
With diisobutylaluminium hydride In toluene at -78 - 20℃; | ||
27 Preparation of 2-(1'-ethenecyclohexyl)-3-hydroxy-naphthalene-1.4-dione Example 27 Preparation of 2-(1'-ethenecyclohexyl)-3-hydroxy-naphthalene-1.4-dione (Formula III: n=0; m=0; R1 +R2 together and R7 +R8 together both represent =O; R3 =--OH; --CR4 R5 --=cyclohexyl; R6 =--CH=CH2) To a stirred solution of ethyl cyclohexylideneacetate (see route to this by Wadsworth and Emmons in Org. Synth. Coll. Vol 5 547) (3.00 g, 17.8 mmol) in dry ether (50 ml) under an atmosphere of nitrogen at 0° C. was added lithium aluminium hydride (407 mg, 10.7 mol) portionwise and the mixture stirred for 2 hours before quenching with dilute hydrochloric acid (2M; 20 ml). The mixture was filtered and the aqueous layer was separated and extracted further with ether (2*25 ml) and the combined ether layers washed with water (2*25 ml) and saturated sodium chloride solution (25 ml) and then dried over MgSO4. Filtration and evaporation of the solvent and distillation of the residue gave 2-cyclohexylidene ethanol (2.16 g, bp. 112° C. at 10 mmHg [Kugelrohr]). | ||
With diisobutylaluminium hydride In dichloromethane at -78℃; for 1.5h; Inert atmosphere; | ||
With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 0℃; for 0.5h; | 2 Example 2:- [0042] 2-Cyclohexylideneethan-1-ol (4) To a solution of vitride in toluene at 0°C ( 1 .5 eq), unsaturated ester 5 in toluene was added in drop wise manner, and the solution was stirred at same temperature for 30 min. The reaction was then quenched with saturated sodium potassium tartarate salt and stirred for 3h. The solution was extracted with ethyl acetate (3 χ 100 mL), washed with water followed by brine, dried over anhydrous Na2S04 and filtered. Removal of the ethyl acetate under reduced pressure furnished compound 4 as a clear liquid and was characterized without any purification method (6. 1 g. 97%). Rt-(40% EtOAc/hexane): 0.4. Yield: 97%; IR (CHCI3): 342 1 , 2934. 1 647, 1 705, 1265 cm" 1 ; NMR (200 MHz. Chlroform-i + CC14) δ ppm 1 .48 - 1 .69 (m, 6 H) 2.01 - 2.29 (m, 4 H) 3.50 (s, 1 H) 4. 1 3 (d, J=7.1 Hz, 2 H) 5.36 (tt. .7=7. 1 Hz. I H); 1 C NMR (50 MHz. chloroform-c/+CCI4) δ ppm 26.66, 27.76, 28.32. 28.77. 36.98. 58.21 , 120.47. 143.76. | |
With diisobutylaluminium hydride In toluene at -78℃; for 1h; Inert atmosphere; | General Procedure for Synthesis of Allylic Alcohols General procedure: A two-necked flask was dried using heat gun under reduced pressure and filled with argon. To this flask was added ethyl (E)-3-(4-chlorophenyl)acrylate (1.26 g, 6.0 mmol, 1.0 eq) and the flask was evacuated and refilled with argon (×3). To the flask was added toluene (40 mL) and the solution was cooled to -78 C. DIBAL (11.8 mL, 1.02 M in toluene, 12 mmol, 2.0 eq) was slowly added and the resultant solution was stirred for 1 h at -78 C. To the mixture were added carefully MeOH (10.5 mL) and 30% aq. Rochelle salt (18 mL) successively, and then the mixture was allowed to warm to room temperature. After being stirred for over 30 minutes, the resultant bi-phasic mixture was separated. The organic layer was washed with 30% aq. Rochelle salt and the aqueous layer was extracted with Et2O (×3). Combined organic layer was washed with brine (×1), dried over Na2SO4, and filtered. Volatiles were removed under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: hexane/EtOAc 2:1) to afford the title compound as a white solid in 89% yield (892.8 mg). | |
With diisobutylaluminium hydride In hexane; dichloromethane at -70℃; | ||
With lithium aluminium tetrahydride In diethyl ether at 0℃; for 0.5h; Inert atmosphere; | ||
With diisobutylaluminium hydride In dichloromethane at -70℃; | ||
With diisobutylaluminium hydride In dichloromethane; toluene Cooling with acetone-dry ice; | 4.4.10. (E)-(4-Iodobut-2-en-2-yl)benzene (1j) General procedure: To a cooled (-78 C) solution of 16a (950 mg, 5 mmol) in CH2Cl2 (30 mL) was added DIBAL-H (1.2 M in toluene, 9 mL, 11 mmol). When the reduction was complete, the reaction was quenched by Na2SO410H2O (4.8 g, 15 mmol). When a precipitate appeared, the mixture was diluted with Et2O (50 mL) and stirred for 1 h. Solids were filtered off and washed with Et2O (50 mL x 3). After drying over anhydrous Na2SO4, the solution was concentrated to afford (E)-3-phenylbut-2-en-1-ol (17a) as a crude oil, which underwent an iodination to afford desired 1j as a yellow oil, 460 mg (2 mmol scale), 89% yield. | |
With diisobutylaluminium hydride In toluene at -70℃; Sealed tube; | ||
With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 15h; Inert atmosphere; | ||
With lithium aluminium tetrahydride In diethyl ether at 0℃; for 1h; Inert atmosphere; | ||
With diisobutylaluminium hydride In toluene at -78 - 20℃; for 3h; | ||
With diisobutylaluminium hydride In tetrahydrofuran at -78℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In toluene for 24h; Reflux; | |
87% | In xylene for 6h; reflux; | |
85% | for 0.05h; microwave irradiation; |
82% | In xylene for 24h; Heating; | |
80% | With benzoic acid In benzene for 48h; Heating; | |
62% | In acetonitrile at 190℃; for 0.333333h; microwave irradiation; | |
With benzoic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With Fe(TCP)Cl; polyethylene supported arsine; polymethylhydrosiloxane In toluene at 110℃; for 12h; Inert atmosphere; | |
88% | With tributylstibine In benzene at 50℃; for 6h; | |
83% | With meso-tetrakis(tetraphenyl)porphyrin iron(III) chloride; triphenylphosphine; benzoic acid In toluene at 80℃; for 24h; |
80% | With copper(l) iodide; dibutyl telluride at 50℃; | |
71% | With triphenylphosphine; benzoic acid In toluene at 80℃; for 50h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In dichloromethane at 15℃; for 9h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 85% 2: 5% | With n-butyllithium In tetrahydrofuran at -78 - 15℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With hydrogenchloride In ethanol at 25℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In tetrahydrofuran at -78℃; for 0.583333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With trifluoroacetic anhydride In dichloromethane at -78℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogen In methanol for 5h; | |
95% | With CuF(PPh3)3*2MeOH; bis[2-(diphenylphosphino)phenyl] ether In toluene at 25℃; for 19h; Inert atmosphere; chemoselective reaction; | |
With palladium on activated charcoal; hydrogen In ethanol at 20℃; for 5h; |
With hydrogen In toluene at 150℃; for 15h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 13% 2: 74% | With ammonia In methanol at 140℃; for 72h; | |
1: 35% 2: 53% | With ammonia In methanol at 135℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With ammonia In methanol at 140℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With Phenylselenyl chloride; zinc(II) chloride In dichloromethane at 20℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With chloro-trimethyl-silane In diethyl ether; dichloromethane at -78 - 0℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With hydrazine hydrate In methanol Heating; | |
With hydrazine hydrate In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium phosphate; 1,3-(4-Ph-OMe)2-5-Ph-1,3,4-triazinium perchlorate In 1,2-dimethoxyethane at 80℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With methanol; water; caesium carbonate In toluene at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: ethanol / 0 - 20 °C 2.2: NaBH4 / ethanol / 0.67 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 89 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / -20 °C 2: 51 percent / NBS / acetonitrile / 20 °C 3: 93 percent / NaH / tetrahydrofuran / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 89 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / -20 °C 2: 51 percent / NBS / acetonitrile / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: ethanol / 0 - 20 °C 2.2: NaBH4 / ethanol / 0.67 h / 0 - 20 °C 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: ethanol / 0 - 20 °C 2.2: NaBH4 / ethanol / 0.67 h / 0 - 20 °C 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: ethanol / 0 - 20 °C 2.2: NaBH4 / ethanol / 0.67 h / 0 - 20 °C 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: ethanol / 0 - 20 °C 2.2: NaBH4 / ethanol / 0.67 h / 0 - 20 °C 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C 4.1: Lewis acid; (S,S)-2,2'-isopropylidene-bis(4-isopropyl-2-oxazoline) / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / Heating 2: K2CO3; NaI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / Heating 2: K2CO3; NaI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / ethanol / Heating 2.1: K2CO3; NaI / acetonitrile / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: tetrahydrofuran / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: 81 percent / 1,3-(4-Ph-OMe)2-5-Ph-1,3,4-triazinium perchlorate; K3PO4 / 1,2-dimethoxy-ethane / 16 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: pyridinium chlorochromate / CH2Cl2 / 3 h / 20 °C 2: tetrahydrofuran / 20 °C 3: 81 percent / 1,3-(4-Ph-OMe)2-5-Ph-1,3,4-triazinium perchlorate; K3PO4 / 1,2-dimethoxy-ethane / 16 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 89 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 3 h / -20 °C 2: 83 percent / mCPBA / CH2Cl2 / 3 h / 20 °C | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / diethyl ether / 10 h / -78 - 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3 h / 20 °C | ||
Multi-step reaction with 2 steps 1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 0.5 h / 0 °C 2: sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 92 percent / hydrazine hydrate / methanol / Heating 2: 86 percent / K2CO3; NaI / butan-2-one / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 86 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 96 percent / tetrahydrofuran / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 92 percent / hydrazine hydrate / methanol / Heating 2: 83 percent / K2CO3; NaI / butan-2-one / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 83 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 92 percent / tetrahydrofuran / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 86 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 96 percent / tetrahydrofuran / -78 °C 4.1: Cu(OTf)2; 2,2-bis[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]propane / CH2Cl2 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 86 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 96 percent / tetrahydrofuran / -78 °C 4.1: Cu(OTf)2; 2,2-bis[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]propane / CH2Cl2 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 86 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 96 percent / tetrahydrofuran / -78 °C 4.1: Cu(OTf)2; 2,2-bis[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]propane / CH2Cl2 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 83 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 92 percent / tetrahydrofuran / -78 °C 4.1: Cu(OTf)2; 2,2-bis[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]propane / CH2Cl2 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 83 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 92 percent / tetrahydrofuran / -78 °C 4.1: Cu(OTf)2; 2,2-bis[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]propane / CH2Cl2 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 92 percent / hydrazine hydrate / methanol / Heating 2.1: 83 percent / K2CO3; NaI / butan-2-one / Heating 3.1: n-BuLi / tetrahydrofuran / 0.5 h / -78 °C 3.2: 92 percent / tetrahydrofuran / -78 °C 4.1: Cu(OTf)2; 2,2-bis[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]propane / CH2Cl2 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether 2: 1.) CH3CH2CO2H, 2.) KOH / 1.) reflux, 2.) MeOH, reflux, 5 h | ||
Multi-step reaction with 2 steps 1.1: diisobutylaluminium hydride / toluene / 3.25 h / -78 - 25 °C / Inert atmosphere 2.1: phenol / 16 h / 160 °C / Dean-Stark 2.2: 1 h / 100 °C / Dean-Stark |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: LiAlH4 / diethyl ether 2: 1.) CH3CH2CO2H, 2.) KOH / 1.) reflux, 2.) MeOH, reflux, 5 h 3: 1.) HOBt, 2.) 1-<3-(dimethylamino)propyl>-3-ethylcarbodiimide / 1.) CH2Cl2, 0 deg C, 5 min, 2.) CH2Cl2, RT, overnight |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: LiAlH4 / diethyl ether 2: 1.) CH3CH2CO2H, 2.) KOH / 1.) reflux, 2.) MeOH, reflux, 5 h 3: 1.) HOBt, 2.) 1-<3-(dimethylamino)propyl>-3-ethylcarbodiimide / 1.) CH2Cl2, 0 deg C, 5 min, 2.) CH2Cl2, RT, overnight 4: 1.) NaH / 1.) THF, RT, 30 min, 2.) THF, RT, overnight |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With two carbon Wittig ylide In toluene at 120℃; for 24h; | 1 Example 1 : [0041] Ethyl 2-cyclohexylideneacetate A clean, dry 250 mL R.B. was charged with cyclo hexanone (5g. 5 1 .00 mmol) and two carbon Wittig yl ide ( 19.537gm, 56. 1 mmol). Then, temperature was raised to 1 20°C. The reaction mixture was refluxed for 24 h. After completion of the reaction, toluene was removed in vacuo. After removal of toluene, it was filtered in 5 % ethyl acetate: pet. ether system through 3 cm thick celite bed to remove triphenyl phosphorous oxide. Filtrate was concentrated under reduced pressure and purification of the residue on a silica gel column chromatography using ethyl acetate/ pet. ether (2:98) gave unsaturated ester 4 (24.7 g, 98%) as a clear liquid. R,-(5% EtOAc/hexane): 0.5. Yield: 98%; 1R (CHC13): 3020, 1705, 1646, 1215 cm" 1 ; NMR (200 MHz, Chloroform-i/+CCl4) δ ppm 1.28 (t, J=7.1 Hz, 3 H) 1.50 - 1 .76 (m, 7 H) 2.10 - 2.27 (m, 2 H) 2.64 - 3.01 (m, 2 H) 4.13 (q, J=7.1 Hz, 2 H) 5.58 (t, J= 1 .0 Hz, 1 H); 13C NMR (50 MHz, CHLOROFORM-d+CCl4) δ ppm 14.15, 26.14, 27.61 , 28.46, 29.55, 37.80, 59.05, 1 12.96, 162.89, 166.28. |
Multi-step reaction with 2 steps 1: diethyl ether; benzene 2: aqueous H2SO4 | ||
Multi-step reaction with 2 steps 1: diethyl ether 2: aqueous HCl |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.4% | With potassium carbonate In nitromethane; water; dimethyl sulfoxide | 2.2 (Step 2) (Step 2) To a mixture of 64.72 g (0.469 mole) potassium carbonate suspended in 469.5 mL dimethyl sulphoxide is measured in, during the course of 1 to 2 hours at 95° C., a solution of 158 g, (0.939 mole) ethyl cyclohexylideneacetate and 85.94 g (1.408 mole) nitromethane. After completion of the addition, stirring is continued at 95° C. for 2 to 3 hours. Subsequently, with ice-water cooling, the reaction solution is acidified with about 150 mL concentrated hydrochloric acid and diluted with 1.5 L of water. The resultant phases are separated and the aqueous phase is extracted several times with petroleum ether. The combined organic phases are washed neutral with water and dried over anhydrous sodium sulphate. The solvent is subsequently distilled off in a vacuum. 190.3 g Ethyl 1-nitromethyl-cyclohexaneacetate in the form of an oil are obtained; yield 88.4% of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.4% | In cyclohexanone; benzene | 20.i Ethyl cyclo hexylidene acetate Example (i) Ethyl cyclo hexylidene acetate Sodium dried benzene (200 ml) was added to a flask containing sodium hydride (16 g; 0.667 mol.) and the flask was flushed with oxygen-free dry nitrogen. To this mixture was added, over 1 hr., triethylphosphonoacetate (164.3 g; 0.667 mol.+10%) keeping the temperature at 0°. The reaction mixture was stirred for an additional hour at 0° and then treated with cyclohexanone (65.4 g.; 0.667 mol.) at the same temperature. After the addition of the cyclohexanone was complete (~40 min.) the mixture was stirred at room temperature for 3 hr.; stirring became difficult after this time due to a gummy precipitate of sodium diethyl phosphate. The mixture was then heated at 60°-65° for 15 min. during which time it was stirred without difficulty. The mixture was cooled to 15° and the benzene solution was decanted and the solid washed with benzene. The combined mother liquor and washings were evaporated to give a pale yellow oil which on distillation gave the title compound (62 g, 55.4%) as a colourless oil, b.p. 86°-88°/2 mm. Hg |
55% | In 1,2-dimethoxyethane; water; cyclohexanone | 2.a (a) (a) Preparation of ethyl cyclohexylideneacetate Triethylphosphonoacetate (2.50 g, 2.21 ml) was added dropwise to a suspension of sodium hydride (80% in oil, 370 mg) in dimethoxyethane (15 ml). The solution was allowed to stir at room temperature under an atmosphere of dry nitrogen or approximately 30 min. When evolution of hydrogen had ceased, cyclohexanone (1.09 g, 1.15 ml) was added dropwise and the reaction mixture was allowed to stir for 5h, the reaction being followed by thin layer chromatography (tlc). After this time water (50 ml) was added and the aqueous layer was extracted with dichloromethane (2*50 ml). The organic layer was dried, filtered and evaporated to leave an oil. This was purified by bulb to bulb distillation (approximately 130° C. at 2 mmHg) to leave the sweet-smelling title compound (a) (1.04 g, 55%). Nmr: δ(CDCl3) 5.6 (1H, m, C=C--H), 4.15 (2H, q, J=7 Hz), OCH2), 2.8 (2H, br t, --C=C--CH2 cis to ester), 2.2 (2H, br t, --C=C--CH2 trans to ester), 1.6 (8H, m, 4*CH2) and 1.3 (3H, t, J=7 Hz, CH2 CH3). IR: νmax (thin film) 2950, 2870, 1715, 1690, 1205, 1155, 1040, 850 and 610 cm-1. |
55% | In 1,2-dimethoxyethane; water; cyclohexanone | 2.a (a) (a) Preparation of ethyl cyclohexylideneacetate Triethylphosphonoacetate (2.50g, 2.21ml) was added dropwise to a suspension of sodium hydride (80% in oil, 370mg) in dimethoxyethane (15 ml). The solution was allowed to stir at room temperature under an atmosphere of dry nitrogen for approximately 30min. When evolution of hydrogen had ceased, cyclohexanone (1.09g, 1.15ml) was added dropwise and the reaction mixture was allowed to stir for 5h, the reaction being followed by thin layer chromatography (tlc). After this time water (50ml) was added and the aqueous layer was extracted with dichloromethane (2x50ml). The organic layer was dried, filtered and evaporated to leave an oil. This was purified by bulb to bulb distillation (approximately 130°C at 2mmHg) to leave the sweet-smelling title compound (a) (1.04g, 55%). Nmr: δ (CDCl3) 5.6 (1H,m, C=C- H), 4.15 (2H,q, J =7Hz, OC H 2), 2.8 (2H, br t, -C=C-C H 2 cis to ester), 2.2 (2H, br t, -C=C-C H 2 trans to ester), 1.6 (8H, m, 4xC H 2) and 1.3 (3H, t, J =7Hz, CH2C H 3). IR: νmax(thin film) 2950, 2870, 2750, 1715, 1690, 1205, 1155, 1040, 850 and 610 cmmin1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In water; benzene | 2.a 2-Cyclohexylidene ethanol (VI) (R1 R2 =spirocyclohexyl) EXAMPLE 2(a) 2-Cyclohexylidene ethanol (VI) (R1 R2 =spirocyclohexyl) A 70% solution (in benzene) of sodium dihydrobisethoxymethoxy aluminate (100g) was added portionwise to ethyl cyclohexylidene acetate (VII) (58.8 g) in dry ether (300 ml) at 0°. The reaction mixture was stirred for 6h at room temperature and the excess reducing agent was destroyed by the addition of water. The solid sodium aluminate was filtered off and the filtrate extracted with ethyl acetate (4 * 50 ml). The combined extracts were washed with brine, dried over sodium sulphate and the solvent evaporated in vacuo. A pale yellow oil was obtained which on distillation gave 2-cyclohexylidene ethanol (VI) (31 g; yield 70%) as a colourless oil, b.p. 80°/2mm Hg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With lithium acetate In N,N-dimethyl-formamide at 0℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium carbonate In isopropyl alcohol at 60℃; for 16h; | Preparation of ethyl 3-(4-chlorophenyl)-l-oxa-2-azaspiro[4.5]dec-2-ene-4-carboxylateA solution of (7^-4-chloro-N-hydroxybenzimidoyl chloride (7.60 g; 40 mmol) and ethyl 2- cyclohexylideneacetate (20.19 g; 120 mmol) in z'-PrOH (100 ml) was treated with sodium carbonate (6.72 g; 80 mmol) and the resulting mixture was heated at 60°C for 16 h.The mixture was quenched with water (100 ml) and diluted with DCM (75 ml). The aqueous layer was extracted with DCM (3x75 ml) and the combined organic layers were dried over Na2S04. The drying agent was filtered off and after concentration, the residue was purified by column chromatography (heptane/ AcOEt = 9/1) to give 9 g of the desired product as a colorless oil (58%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: ethyl cyclohexylideneacetate With diisobutylaluminium hydride In toluene at -78 - 20℃; for 3h; Inert atmosphere; Stage #2: With phosphorus tribromide In diethyl ether at 0℃; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / diethyl ether / 1 h / 0 °C 2: phosphorus tribromide / diethyl ether / 1.5 h / -20 - 20 °C | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 0 °C / Inert atmosphere 2: phosphorus tribromide / diethyl ether / 0 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1: diisobutylaluminium hydride / toluene / 1 h / -78 °C / Inert atmosphere 2: phosphorus tribromide / diethyl ether / 1 h / 0 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / diethyl ether / 0.5 h / 0 °C / Inert atmosphere 2: phosphorus tribromide / diethyl ether / 0 - 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: diisobutylaluminium hydride / tetrahydrofuran; hexane / 1.5 h / -78 - 20 °C 2: hydrogen bromide / water | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / diethyl ether / 2 h / 0 °C 2: phosphorus tribromide / diethyl ether / 1 h / 0 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / diethyl ether / 15 h / 0 - 20 °C / Inert atmosphere 2: phosphorus tribromide / diethyl ether / 0.17 h / 0 °C / Schlenk technique; Inert atmosphere | ||
Multi-step reaction with 2 steps 1: diisobutylaluminium hydride / tetrahydrofuran / 4 h / -78 °C 2: phosphorus tribromide / diethyl ether / 0 °C / Darkness; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: ethyl cyclohexylideneacetate; ethyl 2-sulfanylacetate With piperidine In ethanol at 20℃; for 20h; Stage #2: With sodium ethanolate In ethanol at -25℃; for 2h; Stage #3: With acetic acid In ethanol at -25 - 20℃; | 13.a example 13(step a) intermediate 13-123.0 mL (209.5 mmol) Mercapto acetic acid ethyl ester and 1 .4 mL (14.0 mmol) piperidine are mixed together in ethanol (150 mL). After addition of 23.5 gcyclohexyliden acetic acid ethyl ester (139.7 mmol) the mixture is stirred for 20 h. The reaction mixture is cooled to -25°C and carefully added to 300 mL of a freshly prepared sodium ethanolate solution (6.42 g sodium metal (279.4 mmol) dissolved in 300 mL dry ethanol) at -25°C. After stirring for 2 h the mixture is quenched by slow addition of 16.7 mL (293.4 mmol) glacial acetic acid and warmed up to room temperature. Then the reaction mixture is concentrated in vacuo to give crude product that is purified by MPLC (silica gel, CH/Ethyl acetate 95:5).Mass spectrometry (ESI+): m/z = 243 [M+H]+ TLC (silica gel, CH/ethyl acetate 4:1 ): Rf = 0.73 | |
Stage #1: ethyl cyclohexylideneacetate; ethyl 2-sulfanylacetate With piperidine In ethanol for 20h; Stage #2: With sodium ethanolate In ethanol at -25℃; for 2h; Stage #3: With acetic acid In ethanol at 20℃; | 13.a Step a Intermediate 13-1 23.0 mL (209.5 mmol) Mercapto acetic acid ethyl ester and 1.4 mL (14.0 mmol) piperidine are mixed together in ethanol (150 mL). After addition of 23.5 g cyclohexyliden acetic acid ethyl ester (139.7 mmol) the mixture is stirred for 20 h. The reaction mixture is cooled to -25° C. and carefully added to 300 mL of a freshly prepared sodium ethanolate solution (6.42 g sodium metal (279.4 mmol) dissolved in 300 mL dry ethanol) at -25° C. After stirring for 2 h the mixture is quenched by slow addition of 16.7 mL (293.4 mmol) glacial acetic acid and warmed up to room temperature. Then the reaction mixture is concentrated in vacuo to give crude product that is purified by MPLC (silica gel, CH/Ethyl acetate 95:5). C12H18O3S (242.34) Mass spectrometry (ESI+): m/z=243 [M+H]+ TLC (silica gel, CH/ethyl acetate 4:1): Rf=0.73 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate In tetrahydrofuran Reflux; | 1.3 To 4-(4-chlorophenoxy)-N-hydroxy-benzimidoyl chloride (20.0 g, 0.07 mol) and ethyl 2- cyclohexylideneacetate (30.0 g, 0.17 mol) dissolved in THF (400 ml) was added NaHCO3 (12.0 g, 0.14 mol) and the solution was refluxed overnight. The resulting solution was extracted with MTBE (200 ml_x2), washed with brine, dried over Na2S04 and concentrated then purified by chromatogram on silica gel (PE: EA = 500:1 - 100: 1 ) to afford ethyl 2-[4-(4- chlorophenoxy)phenyl]-4-oxa-3-azaspiro[4.5]dec-2-ene-1 -carboxylate (3.0 g, 10 %) 1H NMR: CDCI3400MHz: 7.58 (d, 2H J= 12 Hz), 7.30 (d, 2H J= 8 Hz), 6.95 (m, 4H), 4.17 (t, 2H J= 14 Hz), 3.92 (s, 1 H), 1 .53-1 .88 (m, 9H), 1 .35 (m, 1 H), 1 .19 (q, 3H J= 4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: diethyl ether / 0.5 h / -78 - 0 °C 2: sodium hydroxide / methanol / 5 h / Reflux | ||
Multi-step reaction with 2 steps 1: chloro-trimethyl-silane / dichloromethane / 17 h / -78 - 20 °C / Schlenk technique; Inert atmosphere 2: sodium hydroxide / methanol; water / 16 h / 60 °C / Schlenk technique; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With iron(III) chloride In benzene at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With iron(III) chloride In benzene at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With iron(III) chloride In benzene at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With iron(III) chloride In benzene at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With titanium tetrachloride; triethylamine In dichloromethane at 0 - 20℃; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With palladium(II) trifluoroacetate; rac-2-((4R,5R)-4,5-diphenyl-1-tosyl-4,5-dihydro-1H-imidazol-2-yl)pyrimidine; oxygen In N,N-dimethyl acetamide at 80℃; for 24h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chloro-trimethyl-silane In dichloromethane at -78 - 20℃; for 17h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With iron(III) chloride In 1,2-dichloro-ethane at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With chloro-trimethyl-silane; sodium iodide In toluene at 80℃; for 5h; Inert atmosphere; | 7 Example 7: Ethyl 2-cyclohexylideneacetate (1.0eq), methyl fluorosulfonyldifluoroacetate (1.2eq) were dissolved in toluene, sodium iodide (2eq) and trimethylsilyl chloride (2eq) were added, nitrogen protection , 80 reaction for 5 hours. The reaction was cooled, water was added, and the toluene layer was removed and dried over anhydrous sodium sulfate. The crude product is purified by the column to obtain the sample 7 of embodiment 7, and the structural formula of the sample 7 is as follows: |
Tags: 1552-92-7 synthesis path| 1552-92-7 SDS| 1552-92-7 COA| 1552-92-7 purity| 1552-92-7 application| 1552-92-7 NMR| 1552-92-7 COA| 1552-92-7 structure
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P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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