Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 72653-21-5 | MDL No. : | MFCD26394906 |
Formula : | C11H16O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CBUZTWMDYDHENI-UHFFFAOYSA-N |
M.W : | 212.24 | Pubchem ID : | 12522245 |
Synonyms : |
|
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
34% | With sodium ethanolate In ethanol at 20℃; for 15h; Inert atmosphere; | |
With sodium ethanolate | ||
2.5 g | With sodium ethanolate In ethanol at 20℃; for 3h; | 512.512A Example 512A: ethyl 4-hydroxy-2-oxobicyclo[2.2.2]octane-l-carboxylate To a solution of ethyl l-acetyl-4-oxocyclohexanecarboxylate (5.0 g, 23.56 mmol) in ethanol (75 mL), sodium ethoxide (1.759 mL, 4.71 mmol) was added to give a brown solution. After 3 hours stirring at ambient temperature, the reaction mixture was concentrated, and the residue was partitioned between saturated citric acid and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel (0-70% ethyl acetate in heptane) to give 2.5 g of the title compound.JH NMR (400 MHz, DMSO-+) m/z 213.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With pyridine; acetic anhydride at 145℃; for 2h; | D28.3 Step 3: ethyl- l-acetyl-4-oxocyclohexanecarboxylate (D28-3) To a stirred suspension of compound D28-2 (85 g, 310 mmol) in acetic anhydride (255 mL) was added pyridine (27 mL) and the mixture was stirred at 145 °C for 2 h. The solvent was removed under reduced pressure, the residue was suspended in water (200 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over Na2S04 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (14% EtOAc/hexane as eluent) to provide compound D28-3 (11 g, 17%) as brown gum. FontWeight="Bold" FontSize="10" H NMR (CDCI3, 400 MHz): δ 4.28 (q, J = 7.2 Hz, 2H), 2.44-2.42 (m, 6H), 2.23-2.20 (m, 5H), 1.31 (t, J = 7.2 Hz, 3H). |
With pyridine; acetic anhydride | ||
Multi-step reaction with 2 steps 1: KOAc/Ac2O / 2 h / Heating 2: 250 - 260 °C / 10 Torr |
With potassium acetate; acetic anhydride at 145℃; for 2h; | 8.3 Step 3: Ethyl l-acetyl-4-oxocvclohexanecarboxyIateTo a stirred suspension of Step 2 product (1 eq) in acetic anhydride (2.5 v/w) under nitrogen was added potassium acetate (0.02 eq). The reaction mixture was heated to, and stirred at the reflux temperature (145°C) for 2 hours. The resultant solution was concentrated in vacuo, and purged with toluene to afford a brown oil. This brown oil was dripped into an evacuated flask (at approximately 10 mmHg pressure) containing sand heated to 250°C; the rate of addition was such that it equalled the rate of pyrolysate collection. Upon complete addition the vacuum was hardened to approximately 3 mmHg pressure, and the pyrolysis continued for a further 30 mins. The pyrolysate was re-distilled at 106 - 110 0C at 0.5 mmHg to give the product as a colourless oil. | |
3.57 g | With potassium acetate In acetic anhydride for 3h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 250 - 260℃; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With toluene-4-sulfonic acid In benzene at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With toluene-4-sulfonic acid In benzene at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 11: 93 percent / NaOMe / methanol / 2 h / Heating 12: 81 percent / SF4 / 24 h / Ambient temperature | ||
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 12: 93 percent / NaOMe / methanol / 2 h / Heating 13: 81 percent / SF4 / 24 h / Ambient temperature | ||
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 11: 93 percent / NaOMe / methanol / 2 h / Heating 12: 81 percent / SF4 / 24 h / Ambient temperature |
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 12: 93 percent / NaOMe / methanol / 2 h / Heating 13: 81 percent / SF4 / 24 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 11: 93 percent / NaOMe / methanol / 2 h / Heating | ||
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 12: 93 percent / NaOMe / methanol / 2 h / Heating | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 11: 93 percent / NaOMe / methanol / 2 h / Heating |
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 12: 93 percent / NaOMe / methanol / 2 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature |
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating | ||
Multi-step reaction with 4 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating | ||
Multi-step reaction with 4 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating |
Multi-step reaction with 3 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating | ||
Multi-step reaction with 7 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating | ||
Multi-step reaction with 6 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating |
Multi-step reaction with 7 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: BH3*SMe2 / tetrahydrofuran / 1 h / Heating | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: BH3*SMe2 / tetrahydrofuran / 1 h / Heating | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: BH3*SMe2 / tetrahydrofuran / 1 h / Heating |
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: BH3*SMe2 / tetrahydrofuran / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride |
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating | ||
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating |
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating | ||
Multi-step reaction with 5 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating | ||
Multi-step reaction with 4 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating |
Multi-step reaction with 5 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating | ||
Multi-step reaction with 3 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature | ||
Multi-step reaction with 6 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature | ||
Multi-step reaction with 5 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature |
Multi-step reaction with 6 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C |
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating 12: concn HCl / CH2Cl2; benzene / 3 h / Heating | ||
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating 13: concn HCl / CH2Cl2; benzene / 3 h / Heating | ||
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating 12: concn HCl / CH2Cl2; benzene / 3 h / Heating |
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating 13: concn HCl / CH2Cl2; benzene / 3 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 34 percent / Pb(OAc)4/N-chlorosuccinimide/glacial AcOH / dimethylformamide / 0.5 h / 50 °C | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 34 percent / Pb(OAc)4/N-chlorosuccinimide/glacial AcOH / dimethylformamide / 0.5 h / 50 °C | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 34 percent / Pb(OAc)4/N-chlorosuccinimide/glacial AcOH / dimethylformamide / 0.5 h / 50 °C |
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 34 percent / Pb(OAc)4/N-chlorosuccinimide/glacial AcOH / dimethylformamide / 0.5 h / 50 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 1.) mercuric oxide, MgSO4, 2.) Br2 / 1.) CH2Cl2, reflux, 30 min, 2.) 2 h | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 1.) mercuric oxide, MgSO4, 2.) Br2 / 1.) CH2Cl2, reflux, 30 min, 2.) 2 h | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 1.) mercuric oxide, MgSO4, 2.) Br2 / 1.) CH2Cl2, reflux, 30 min, 2.) 2 h |
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 1.) mercuric oxide, MgSO4, 2.) Br2 / 1.) CH2Cl2, reflux, 30 min, 2.) 2 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 62 percent / tert-butyl hypoiodite / 1,1,2-trichloro-1,2,2-trifluoro-ethane / 40 - 50 °C / Irradiation | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 62 percent / tert-butyl hypoiodite / 1,1,2-trichloro-1,2,2-trifluoro-ethane / 40 - 50 °C / Irradiation | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 62 percent / tert-butyl hypoiodite / 1,1,2-trichloro-1,2,2-trifluoro-ethane / 40 - 50 °C / Irradiation |
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 62 percent / tert-butyl hypoiodite / 1,1,2-trichloro-1,2,2-trifluoro-ethane / 40 - 50 °C / Irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / Heating | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / Heating | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / Heating |
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 11: 93 percent / NaOMe / methanol / 2 h / Heating 12: 1.) KH / 1.) THF, reflux, 30 min, 2.) 30 min | ||
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 12: 93 percent / NaOMe / methanol / 2 h / Heating 13: 1.) KH / 1.) THF, reflux, 30 min, 2.) 30 min | ||
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating 10: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 11: 93 percent / NaOMe / methanol / 2 h / Heating 12: 1.) KH / 1.) THF, reflux, 30 min, 2.) 30 min |
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating 11: 77 percent / m-chloroperbenzoic acid / CH2Cl2 / 72 h / Ambient temperature 12: 93 percent / NaOMe / methanol / 2 h / Heating 13: 1.) KH / 1.) THF, reflux, 30 min, 2.) 30 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: BH3*SMe2 / tetrahydrofuran / 1 h / Heating 10: pyridinium chlorochromate / CH2Cl2 / 1 h / Heating | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: BH3*SMe2 / tetrahydrofuran / 1 h / Heating 11: pyridinium chlorochromate / CH2Cl2 / 1 h / Heating | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: BH3*SMe2 / tetrahydrofuran / 1 h / Heating 10: pyridinium chlorochromate / CH2Cl2 / 1 h / Heating |
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: BH3*SMe2 / tetrahydrofuran / 1 h / Heating 11: pyridinium chlorochromate / CH2Cl2 / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: dry NH3 / diethyl ether / 0 °C 11: 82 percent / (CF3CO)2O / pyridine; dioxane | ||
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: dry NH3 / diethyl ether / 0 °C 12: 82 percent / (CF3CO)2O / pyridine; dioxane | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: dry NH3 / diethyl ether / 0 °C 11: 82 percent / (CF3CO)2O / pyridine; dioxane |
Multi-step reaction with 12 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: dry NH3 / diethyl ether / 0 °C 12: 82 percent / (CF3CO)2O / pyridine; dioxane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: 90 percent / diethyl ether; hexane / 2 h / Heating |
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: 90 percent / diethyl ether; hexane / 2 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: dry NH3 / diethyl ether / 0 °C | ||
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: dry NH3 / diethyl ether / 0 °C | ||
Multi-step reaction with 10 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: dry NH3 / diethyl ether / 0 °C |
Multi-step reaction with 11 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: dry NH3 / diethyl ether / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature | ||
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature | ||
Multi-step reaction with 8 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature |
Multi-step reaction with 9 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating 12: concn HCl / CH2Cl2; benzene / 3 h / Heating 13: 58 percent / KMnO4, MgSO4 / acetone; H2O / 48 h / Ambient temperature | ||
Multi-step reaction with 14 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating 13: concn HCl / CH2Cl2; benzene / 3 h / Heating 14: 58 percent / KMnO4, MgSO4 / acetone; H2O / 48 h / Ambient temperature | ||
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating 12: concn HCl / CH2Cl2; benzene / 3 h / Heating 13: 58 percent / KMnO4, MgSO4 / acetone; H2O / 48 h / Ambient temperature |
Multi-step reaction with 14 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating 13: concn HCl / CH2Cl2; benzene / 3 h / Heating 14: 58 percent / KMnO4, MgSO4 / acetone; H2O / 48 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature | ||
Multi-step reaction with 8 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature | ||
Multi-step reaction with 7 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature |
Multi-step reaction with 8 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating 12: concn HCl / CH2Cl2; benzene / 3 h / Heating 13: 65 percent / acetic acid / 1 h / Heating | ||
Multi-step reaction with 14 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating 13: concn HCl / CH2Cl2; benzene / 3 h / Heating 14: 65 percent / acetic acid / 1 h / Heating | ||
Multi-step reaction with 13 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 5: 92 percent / BF3*OEt2 / Ambient temperature 6: 94 percent / NaOMe / methanol / 2 h / Heating 7: 92 percent / SF4 / 24 h / Ambient temperature 8: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 9: thionyl chloride 10: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 11: CH2Cl2; benzene / 2 h / Heating 12: concn HCl / CH2Cl2; benzene / 3 h / Heating 13: 65 percent / acetic acid / 1 h / Heating |
Multi-step reaction with 14 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature 3: hydrazine hydrate, KOH / bis-(2-hydroxy-ethyl) ether / 10 h / Heating 4: KOH / bis-(2-hydroxy-ethyl) ether / Heating 5: 91 percent / concn H2SO4 / 1,2-dichloro-ethane / 20 h / Heating 6: 92 percent / BF3*OEt2 / Ambient temperature 7: 94 percent / NaOMe / methanol / 2 h / Heating 8: 92 percent / SF4 / 24 h / Ambient temperature 9: 96 percent / H2O/KOH / ethanol / 16 h / Ambient temperature 10: thionyl chloride 11: NaN3 / acetone; H2O / 1 h / 0 - 5 °C 12: CH2Cl2; benzene / 2 h / Heating 13: concn HCl / CH2Cl2; benzene / 3 h / Heating 14: 65 percent / acetic acid / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: methanol 2: H2O/KOH / ethanol / 16 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride at 5℃; for 2.5h; Heating / reflux; | 8.4 Step 4: Ethyl 4-methoxy-2-oxo-bicvcIo[2.2.21octane-l-carboxylateTo a stirred solution of Step 3 product (1 eq) and trimethyl orthoformate (4.00 eq) in MeOH (9.4 v/w) at 5°C was bubbled HCl gas (approximately 5 eq) over 2 hours, maintaining a pot temperature of 5°C. Upon complete addition, the reaction mixture, under nitrogen, was heated to, and stirred at, reflux for 30 minutes.The resultant purple solution was cooled to approximately 30°C and concentrated in vacuo. The residue was partitioned between saturated aqueous NaHCO3 (20 v/w) and MTBE (8 v/w), and the separated aqueous layer extracted further with MTBE (3 x 8 v/w). The combined organic phases were washed with brine (12 v/w), dried over MgSO4, filtered and concentrated in vacuo to afford the product as an amber oil which partially crystallised on standing. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene for 7h; Reflux; Dean-Stark conditions; Stage #2: With hydrogenchloride In water; toluene at 20℃; for 0.5h; Stage #3: With sodium hydroxide In water; toluene | 3 Example 3 (Steps 1 and 2): 4-(Benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylic acid ethyl ester Toluene (310 mL) was added to 1-acetyl-4-oxocyclohexyl carboxylic acid ethyl ester (31.0g, 146 mmol) and then the resulting mixture was stirred. To the mixture, there were added benzylamine (48.0 mL, 438 mmol) and p-toluenesulfonic acid monohydrate (251 mg, 1.32 mmol). The mixture was refluxed for 7 hours with a Dean-Stark apparatus under the dehydration conditions. The mixture was cooled to 20°C, a 3 mol/L hydrochloric acid solution (155 g) was added dropwise to the mixture and then the resulting mixture was stirred for 0.5 hours. To the mixture, there was added dropwise a 6 mol/L aqueous sodium hydroxide solution, followed by stirred for 10 minutes and the organic phase was separated. The resulting organic phase was washed twice with 155 g of a 18% aqueous ammonium chloride solution and further washed with 62 g of water. The organic phase was subjected to quantitative analysis (according to the LC technique) and as a result, the yield of the desired product was found to be 95% (the internal standard substance used was m-xylene). |
85% | With toluene-4-sulfonic acid In toluene for 8h; Reflux; Dean-Stark; | D28.4 Step 4: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate (D28-4) To a stirred mixture of compound D28-3 (25.0 g, 117 mol) and benzyl amine (38.6 mL, 353 mol) in toluene (250 mL) was added p-TsOH (0.22 g, 1.17 mmol), and the mixture was refluxed for 8 h in a flask equipped with a Dean-Stark adapter. The reaction mixture was cooled to room temperature. HC1 (3 M, 250 mL) was added to the reaction mixture, and the whole was stirred for 30 min. The mixture was neutralized with aqueous solution of 6 M NaOH to pH 7. The reaction mixture was extracted with EtOAc (3 x 100 mL). The combined organic extracts were washed with water (100 mL), brine (100 mL), dried over Na2S04 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50% EtOAc/hexane as eluent) to provide compound D28-4 (30 g, 85%) as an off-white solid. NMR (CDC13, 400 MHz): δ 7.40-7.21 (m, 5H), 6.44-6.32 (m, 2H), 4.20 (q, J = 7.2 Hz, 2H), 3.74 (s, 1H), 2.45 (s, 2H), 2.30-2.20 (m, 2H), 2.10-1.95 (m, 2H), 1.89-1.75 (m, 4H), 1.27 (t, J = 6.8 Hz, 3H). |
20% | With toluene-4-sulfonic acid In toluene for 24h; Dean-Stark; Reflux; | 80.1 Example 80: 4-((6-(trans-4-tert-Butylcyclohexyloxy)naphthalen-2-yl)methylamino)-2-hyd] clo[2.2.2]octane-l-carboxylic acid Step 1: Ethy -(benzylamino)-2-oxobicvclor2.2.21octane-l-carboxylate Example 80: 4-((6-(trans-4-tert-Butylcyclohexyloxy)naphthalen-2-yl)methylamino)-2-hyd] clo[2.2.2]octane-l-carboxylic acid Step 1: Ethy -(benzylamino)-2-oxobicvclor2.2.21octane-l-carboxylate Ethyl l-acetyl-4-oxocyclohexanecarboxylate (4.3 g, 20.0 mmol, 1.0 eq), PTSA (350 mg, 2.0 mmol, 0.1 eq) and benzylamine (2.4 g, 22.0 mmol, 1.1 eq) were dissolved in toluene (250 mL). The mixture was heated to reflux with dean stark trap for 24 h. The mixture was diluted with H20 (500 mL) and extracted with EtOAc (500 mL x2). The combined organic layers were dried over anhydrous Na2S04 and filtered, concentrated in vacuo to yield a crude product, which was purified by column chromatography on silica gel (DCM/MeOH = 20: 1), then followed by recrystallization from petroleum ether and ErtOAc to give the title compound as a yellow solid (1.3 g, Y: 20%). LCMS m/z 302.2 [M+l] +; 1H NMR (400 MHz, CDC13) δ: 9.68 (bs, 1H), 7.35 (bs, 5H), 4.23 (q, / = 7.2 Hz, 2H), 3.85 (s, 2H), 2.55 (s, 2H), 2.23-2.17 (m, 2H), 1.93-1.64 (m, 6H), 1.30 (t, / = 7.2 Hz, 3H). Step 2: Ethyl 4-amino-2-oxobicvclor2.2.21octane-l-carboxylate A solution of ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate (500 mg, 1.66 mmol, 1.0 eq) in MeOH (10 mL) was purged with N2 for 3 times. Pd/C (50 mg, 10% w/w) was added, and the mixture was purged with H2 for 2 times. The resulting mixture was stirred at rt under a H2 balloon for 16 h, and then filtered. The filtrate was concentrated in vacuo to get the title compound (280 mg 80%) as a white solid. LCMS m/z 212.1 [M+H] +; 1H NMR (400 MHz, DMSO-d6) δ 8.42 (bs, 2H), 4.10 (q, / = 7.2 Hz, 2H), 2.63 (bs, 2H), 2.15-1.89 (m, 8H), 1.17 (t, / = 7.2 Hz, 3H). Step 3: Ethyl 4-amino-2-hydroxybicyclor2.2.21octane-l-carboxylate A mixture of ethyl 4-amino-2-oxobicyclo[2.2.2]octane-l-carboxylate (200 mg, 0.47 mmol, 1.0 eq) and NaBH4 (18 mg, 0.47 mmol, 1.0 eq) in EtOH (10 mL) was stirred at 0 °C for 30 min. Then the reaction was quenched with water (5 mL) and extracted with EtOAc (8 mL x3). The organic phase was concentrated in vacuo to give the title compound as a white solid (163 mg, 41% yield), which was used in next step without further purification. LCMS m/z 214.1 [M+H] +. Step 4: Ethyl 4-((6-(trans-4-tert-butylcvclohexyloxy)naphthalen-2-yl)methylamino)-2-hvdroxybicyclor A mixture of ethyl 4-amino-2-hydroxybicyclo[2.2.2]octane-l-carboxylate (163 mg, 0.77mol, 1.0 eq), 6-(trans-4-tert-butylcyclohexyloxy)-2-naphthaldehyde (239 mg, 0.77 mmol, 1.0 eq) and AcOH (139 mg, 2.31 mmol, 3.0 eq) in DCE (5 mL) was heated to reflux for 30 min. After cooling down to rt, NaBH(OAc)3 (490 mg, 2.31 mmol, 3.0 eq) was added and the mixture was stirred for additional 16 h at rt. The reaction was then quenched with water (5 mL) and extracted with DCM (5 mL x 3). The combined organic phase was concentrated in vacuo, and the residue was purified by prep-HPLC (MeOH/H20 from 30% to 95%, containing 0.05% TFA) to give the title compound as a white solid (169 mg, 35% yield). LCMS m/z 508.3 [M+l] +; Step 5: 4-((6-(trans-4-tert-Butylcyclohexyloxy)naphthalen-2-yl)methylamino)-2-hydroxybicyclor 2.2.21octane-l-carboxylic acid To a mixture of ethyl 4-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)-2-hydroxybicyclo[ 2.2.2]octane-l-carboxylate (169 mg, 0.33 mmol, 1.0 eq) in a mixed solvent (EtOH/H20 = 4:1, 5 mL) was added NaOH (26 mg, 0.66 mmol, 2.0 eq), the resulting mixture was heated to reflux for 16 h. After cooling down to rt, the reaction mixture was then adjusted to pH = 6 with dilute aq. HC1 (2 M). The resulting suspension was filtered, and the filtrate was purified by prep-HPLC (MeOH/H20 from 30% to 95%, containing 0.05% TFA) to yield the title compound as a yellow solid (84 mg, 52% yield). LCMS m/z 480.3 [M+l] +; 1H NMR (400 MHz, DMSO-J6) δ 7.82-7.76 (m, 3H), 7.48 (d, /= 8.4 Hz, 1H), 7.35 (d, J = 2.4 Hz, 1H), 7.13 (dd, /= 8.8, 2.4 Hz, 1H), 4.37-4.36 (m, 1H), 4.10-4.08 (m, 1H), 3.96 (s, 2H), 2.21-2.11 (m, 4H), 1.83-1.55 (m, 10H), 1.36-1.07 (m, 5H), 0.88 (s, 9H). |
0.77 g | With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; | 65.65D Example 65D: ethyl 4-(benzylamino)-2-oxobicyclo [2.2.2] octane-1 -carboxylate A mixture of Example 65C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and />-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C with Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl (0781) acetate/heptane, and air-dried to give 1 1.3 g of title compound as a HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL χ 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid. XH NMR (400 MHz, DMSO-c) δ ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ES ) m/z 302.1 (M+H)+. |
0.77 g | With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; | 7D Example 7D: ethyl 4-”benzylamino)-2-oxobicyclo[2. 2. 2]octane-1-carboxylate A mixture of Example 7C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, air-dried to give 11.3 g of title compound as a HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound asyellow solid. ‘H NMR (400 MHz, DMSO-d6) 5 ppm 9.73 (t, J 6.2 Hz, 2H), 7.87 - 7.12 (m,5H), 4.09(m, 4H), 2.88 (s, 2H), 2.08 (dt,J 20.7, 13.4 Hz, 6H), 1.16 (t,J 7.1 Hz, 3H); MS(ESI) m/z 302.1 (M+H). |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With p-toluenesulfonic acid monohydrate In toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride In water; ethyl acetate for 0.5h; | 65D Example 65D: ethyl 4-(benzylamino)-2-oxobicyclo[2. 2. 2]octane-] -carboxylate A mixture of Example 65C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C with Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of title compound as a HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellowsolid. ‘H NMR (400 MHz, DMSO-d6) 5 ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 -7.12 (m, 5H), 4.09(m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESf) m/z302.1 (M+H). |
0.77 g | With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; | 1.1D Example ID: ethyl 4-(henzylamino)-2-oxohicyclo[2.2.2]octane-l-carhoxylate A mixture of Example 1C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /i-tolucncsulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated under reduced pressure, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with a mixture of ethyl acetate/heptane and air-dried to give 11.3 g of title compound as an HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL c 2). The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered under reduced pressure. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid. NMR (400 MHz, DMSO-rZs) d ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / toluene / 7 h / Reflux; Dean-Stark conditions 1.2: 0.5 h / 20 °C 2.1: ethanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3.1: triethylamine / toluene; tetrahydrofuran / 1.5 h 4.1: sodium iodide; N,N-dimethyl acetamide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 43 h / 120 °C 5.1: hydrogen / palladium on carbon / toluene; ethanol / 7 h / 20 °C | ||
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / toluene / 8 h / Dean-Stark conditions 2: ethanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3: triethylamine / toluene; tetrahydrofuran / 1.5 h 4: sodium iodide; N,N-dimethyl acetamide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 43 h / 120 °C 5: hydrogen / palladium on carbon / toluene; ethanol / 7 h / 20 °C | ||
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / toluene / 8 h / Reflux; Dean-Stark 2: sodium tetrahydroborate / ethanol / 0.5 h / 0 - 20 °C 3: triethylamine / toluene; tetrahydrofuran / 1 h / 0 - 20 °C 4: sodium iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene; N,N-dimethyl acetamide / 43 h / 120 °C 5: hydrogen; palladium 10% on activated carbon / methanol / 5 h / 760.05 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 7 h / Reflux; Dean-Stark conditions 1.2: 0.5 h / 20 °C 2.1: ethanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3.1: triethylamine / toluene; tetrahydrofuran / 1.5 h | ||
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 8 h / Dean-Stark conditions 2: ethanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3: triethylamine / toluene; tetrahydrofuran / 1.5 h | ||
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 8 h / Reflux; Dean-Stark 2: sodium tetrahydroborate / ethanol / 0.5 h / 0 - 20 °C 3: triethylamine / toluene; tetrahydrofuran / 1 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / toluene / 7 h / Reflux; Dean-Stark conditions 1.2: 0.5 h / 20 °C 2.1: ethanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3.1: triethylamine / toluene; tetrahydrofuran / 1.5 h 4.1: sodium iodide; N,N-dimethyl acetamide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 43 h / 120 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 8 h / Dean-Stark conditions 2: ethanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3: triethylamine / toluene; tetrahydrofuran / 1.5 h 4: sodium iodide; N,N-dimethyl acetamide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 43 h / 120 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 8 h / Reflux; Dean-Stark 2: sodium tetrahydroborate / ethanol / 0.5 h / 0 - 20 °C 3: triethylamine / toluene; tetrahydrofuran / 1 h / 0 - 20 °C 4: sodium iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene; N,N-dimethyl acetamide / 43 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In toluene for 8h; Dean-Stark conditions; | 1 Example 1 (Steps 1 and 2): 4-(Benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylic acid ethyl ester Toluene (100 mL) was added to 1-acetyl-4-oxocyclohexyl carboxylic acid ethyl ester (8.0g, 38 mmol) and then the resulting mixture was stirred. To the mixture, there were added benzylamine (5.3 mL, 49 mmol) and p-toluenesulfonic acid monohydrate (76 mg, 0.40 mmol). The mixture was refluxed for 8 hours with a Dean-Stark apparatus under the dehydration conditions. After cooled to room temperature, the mixture was concentrated under reduced pressure to give a crude product. The resulting crude product was treated according to the silica gel column chromatography (eluting solution: hexane/ethyl acetate) to thus obtain a mixture of the desired product and an imine derivative thereof. The mixture was dissolved in chloroform (200 mL) and then the resulting solution was treated with a 0.5 mol/L hydrochloric acid solution (100 mL). The suspended organic phase was separated, then treated with a 5% aqueous solution of sodium hydrogen carbonate and then separated. The organic phase was dried over anhydrous magnesium sulfate, followed by the removal of the drying agent through filtration and the subsequent concentration of the resulting filtrate under reduced pressure to thus give the desired product as a white solid. (2.9 g; yield: 26%). 1H-NMR (300 MHz, ppm in CDCL3) δ: 1.27 (t, 3H), 1.75-1.89 (m, 4H), 1.95-2.10 (m, 2H), 2.20-2.30 (m, 2H), 2.45 (s, 2H), 3.74 (s, 2H), 4.21 (q, 2H), 7.21-7.40 (m, 5H). LC/MS (ESI+) m/z: 302 (MH+). GC/MS (CI) m/z: 302 (MH+).Analysis of Imine Derivative: LC/MS (ESI+) m/z: 391 (MH+). GC/MS (CI) m/z: 391 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C |
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: N-ethyl-N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / Reflux; Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 - 5 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / lithium hydroxide monohydrate; propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / lithium hydroxide monohydrate; toluene / 3 h / Reflux; Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / ethylene glycol; toluene / 3 h / Reflux; Dean-Stark 2.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one; lithium hydroxide monohydrate / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / Dean-Stark; Reflux 2.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 - 5 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / lithium hydroxide monohydrate; toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: lithium hydroxide monohydrate; hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / 120 °C / Dean-Stark 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / Dean-Stark; Reflux 2.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C 3.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / Dean-Stark 2.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: hydrogenchloride / lithium hydroxide monohydrate; propan-2-one / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 3 h / Dean-Stark; Reflux 2.1: N-ethyl-N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 2.2: 2 h / -70 - -60 °C / Inert atmosphere 3.1: hydrogenchloride / propan-2-one / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C |
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 - 5 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / lithium hydroxide monohydrate; propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one; lithium hydroxide monohydrate / 20 °C | ||
Multi-step reaction with 2 steps 1.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 - 5 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: lithium hydroxide monohydrate; hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C 2.1: hydrogenchloride / propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: n-butyllithium; N,N-diisopropylamine / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: hydrogenchloride / lithium hydroxide monohydrate; propan-2-one / 20 °C | ||
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 0.5 h / -78 - 5 °C / Inert atmosphere 1.2: 2 h / -70 - -60 °C / Inert atmosphere 2.1: hydrogenchloride / propan-2-one / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In propan-2-one at 20℃; | 65.65C Example 65C: ethyl l-acetyl-4-oxocyclohexane-l-carboxylate A mixture of Example 65B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound as a clear oil, used without further purification. XH NMR (400 MHz, DMSO-c) δ ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). | |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 173C Example 173C: ethyl l-acetyl-4-oxocyclohexanecarboxylate Example 173C: ethyl l-acetyl-4-oxocyclohexanecarboxylate A mixture of Example 173B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. The mixture was concentrated, and the residue was taken up in dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound that was used without further purification. XH NMR (400 MHz, OMSO-d6) δ ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 7C Example 7C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 7B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound as a clear oil, used without further purification. ‘H NMR (400 MHz, DMSO-d6) 5 ppm 4.16 (q, J 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t,J 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 68C Example 68C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 68B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound as a clear oil, used without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.352.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
With hydrogenchloride In propan-2-one at 20℃; | 2C Example 2C: ethyl 1 -acetyl-4-oxocyclohexane-l -carboxylate A mixture of Example 2B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound that was used without further purification. H NMR (400 MHz, DMSO-i) δ ppm 4.16 (q, / = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, / = 7.1 Hz, 3H). | |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 173.173C; 198.198C Example 173C: ethyl l-acetyl-4-oxocyclohexanecarboxylate A mixture of Example 173B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. The mixture was concentrated, and the residue was taken up in dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound that was used without further purification.JH NMR (400 MHz, DMSO- e) δ ppm 4.16 (q, / = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, / = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In lithium hydroxide monohydrate; propan-2-one at 20℃; | 65C Example 65C: ethyl ]-acetyl-4-oxocyclohexane-]-carboxylate A mixture of Example 65B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) inacetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. Theorganic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate wasconcentrated to give 5.46 g of the title compound as a clear oil, used without further purification. ‘H NMR (400 MHz, DMSO-d6) 5 ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 10.10C Example 10C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 10B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichlorome thane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound which was used without further purification.JH NMR (400 MHz, DMSO-δ ppm 4.16 (q, / = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In lithium hydroxide monohydrate; propan-2-one at 20℃; | 1C Example 1 C: ethyl 1 -acetyl-4-oxocyclohexane-] -carboxylate A mixture of Example IB (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound which was used without further purification. H NMR (400 MHz, DMSO-i) δ ppm 4.16 (q, J = 1.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, / = 7.1 Hz, 3H). |
6.46 g | With hydrogenchloride In propan-2-one at 20℃; | 10C Example IOC: ethyl l-acetyl-4-oxocyclohexane-l-carboxylate A mixture of Example 10B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound that was used without further purification. H NMR (400 MHz, DMSO-d6) δ ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, 7 = 7.1 Hz, 3H). |
With hydrogenchloride In propan-2-one at 20℃; | 68.68C Example 68C: ethyl l-acetyl-4-oxocyclohexane-l-carboxylate A mixture of Example 68B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichlorome thane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound as a clear oil, used without further purification. JH NMR (400 MHz, DMSO- | |
With hydrogenchloride; lithium hydroxide monohydrate In propan-2-one at 20℃; | 7.C; 174.C Example 7 C: ethyl l-acetyl-4-oxocyclohexane-l-carboxylate A mixture of Example 7B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichlorome thane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound as a clear oil, used without further purification. JH NMR (0845) (400 MHz, DMSO- ) δ ppm 4.16 (q, / = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, / = 7.1 Hz, 3H). | |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 1.1C Example 1C: ethyl l-acetyl-4-oxocyclohexane-l-carboxylate A mixture of Example 1B (6.5 g, 25.4 mmol) and HC1 (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 5.46 g of the title compound as a clear oil which was used without further purification. NMR (400 MHz, DMSO-cfe) d ppm 4.16 (q, J = 7.1 Hz, 2H), 2.35 2.07 (m, 8H), 2.17 (s, 3H), 1.17 (t, J = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 2.C Example 2C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 2B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound that was used without further purification.1H NMR (400 MHz, DMSO-d6) d ppm 4.16 (q, J = 7.1Hz, 2H), 2.17 (s, 3H), 2.352.07 (m, 8H), 1.17 (t, J = 7.1Hz, 3H). |
5.46 g | With hydrogenchloride In lithium hydroxide monohydrate; propan-2-one at 20℃; | 13.13C Example 13C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 13B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 5.46 g of the title compound which was used without further purification.1H NMR (400 MHz, DMSO-d6) d ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.352.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 13C Example 13C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 13B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated to give 5.46 g of the title compound which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
5.46 g | With hydrogenchloride In propan-2-one at 20℃; | 13C Example 13C: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate A mixture of Example 13B (6.5 g, 25.4 mmol) and HCl (21.13 mL, 127 mmol) in acetone (60 mL) was stirred at ambient temperature overnight. Volatiles were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated to give 5.46 g of the title compound which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.16 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.35 2.07 (m, 8H), 1.17 (t, J = 7.1 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr | ||
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: hydrogen; 20% palladium hydroxide-activated charcoal / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr | ||
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / toluene / Reflux; Dean-Stark 1.2: 0.5 h 2.1: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr |
Multi-step reaction with 2 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 130 °C / Dean-Stark 1.2: 0.5 h 2.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr | ||
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / water; toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr | ||
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C | ||
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: hydrogen; 20% palladium hydroxide-activated charcoal / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 16 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / Reflux; Dean-Stark 1.2: 0.5 h 2.1: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C |
Multi-step reaction with 3 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 130 °C / Dean-Stark 1.2: 0.5 h 2.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C | ||
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C | ||
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / water; toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C | ||
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium hydroxide / methanol / 16 h / 20 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: hydrogen; 20% palladium hydroxide-activated charcoal / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium hydroxide; methanol / 16 h / 20 °C | ||
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / toluene / Reflux; Dean-Stark 1.2: 0.5 h 2.1: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium hydroxide / methanol / 16 h / 20 °C |
Multi-step reaction with 4 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 130 °C / Dean-Stark 1.2: 0.5 h 2.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium hydroxide / methanol / 16 h / 20 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium hydroxide; methanol / 16 h / 20 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / water; toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium hydroxide; methanol / 16 h / 20 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium hydroxide; methanol / 16 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium tetrahydroborate; ethanol / 3 h / 0 °C | ||
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: hydrogen; 20% palladium hydroxide-activated charcoal / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium tetrahydroborate / dichloromethane / 1.5 h | ||
Multi-step reaction with 4 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 130 °C / Dean-Stark 1.2: 0.5 h 2.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium tetrahydroborate / ethanol / 3 h / 0 °C |
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / water; toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium tetrahydroborate; methanol / dichloromethane / 1.5 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium tetrahydroborate; ethanol / 3 h / 0 °C 5: hydrazine hydrate / 3 h / 50 °C 6: potassium hydroxide / methanol / 12 h / 80 °C 7: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C 8: acetic acid; potassium permanganate / water / 2 h / 0 °C 9: potassium carbonate / N,N-dimethyl-formamide / 16 h / 40 °C | ||
Multi-step reaction with 10 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 130 °C / Dean-Stark 1.2: 0.5 h 2.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium tetrahydroborate / ethanol / 3 h / 0 °C 5.1: hydrazine hydrate / 3 h / 50 °C 6.1: potassium hydroxide / methanol / 12 h / 20 - 80 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C 8.1: 2,6-dimethylpyridine / dichloromethane / 2 h / 0 °C / Inert atmosphere 9.1: potassium permanganate / water; acetic acid / 2 h / 0 °C / Inert atmosphere 10.1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 50 °C 10.2: 16 h / 20 °C | ||
Multi-step reaction with 9 steps 1.1: p-toluenesulfonic acid monohydrate / toluene / 130 °C / Dean-Stark 1.2: 0.5 h 2.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium tetrahydroborate / ethanol / 3 h / 0 °C 5.1: hydrazine hydrate / 3 h / 50 °C 6.1: potassium hydroxide / methanol / 12 h / 20 - 80 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C 8.1: potassium permanganate / water; acetic acid / 2 h / 0 °C 9.1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 20 - 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.3 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate for 0.5h; | 173D Example 173D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate Example 173D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate (1241) A mixture of ethyl l -acetyl-4-oxocyclohexanecarboxylate (Example 173C, 9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /?-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C in a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of 50 mL of ethyl acetate and 100 mL of 3 N aqueous HCl for 30 minutes. The precipitate was collected by filtration, washed with a mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of the title compound as a hydrochloride salt. The filtrate was neutralized with 6 N aqueous NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid. l NMR (400 MHz, DMSO-c) δ ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H). MS (ESI+) m/z 302.1 (M+H)+. |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate | 68D Example 68D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylate, hydrochloric acid A mixture of Example 68C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C with Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HCl (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, air-dried to give 11.3 g of title compound as an HCl salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL × 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87- 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
0.77 g | With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; | 2D Example 2D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate, hydrochloric acid A mixture of Example 2C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl (0828) acetate/heptane, and air-dried to give 11.3 g of title compound as an HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound. H NMR (400 MHz, DMSO-i) δ ppm 9.73 (t, / = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, / = 20.7, 13.4 Hz, 6H), 1.16 (t, / = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate for 0.5h; Dean-Stark; | 173.173D; 198.198D Example 173D: ethyl 4-(benzylamino )-2-oxobicyclo[ 2.2.2 ] octane- 1 -carboxy late A mixture of ethyl l-acetyl-4-oxocyclohexanecarboxylate (Example 173C, 9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /?-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C in a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of 50 mL of ethyl acetate and 100 mL of 3 N aqueous HC1 for 30 minutes. The precipitate was collected by filtration, washed with a mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of the title compound as a hydrochloride salt. The filtrate was neutralized with 6 N aqueous NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid.JH NMR (400 MHz, DMSO-+. |
12.07 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene Reflux; Dean-Stark; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate for 0.5h; | 10.10D Example 10D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylate hydrochloric acid A mixture of Example IOC (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /?-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethylacetate/heptane, and air-dried to give 11.3 g of the title compound as an HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound.JH NMR (400 MHz, DMSO- |
12.07 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene Reflux; Dean-Stark; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate for 0.5h; | 1D Example ID: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate, hydrochloric acid A mixture of Example 1C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of the title compound as an HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound. H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (t, / = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, / = 20.7, 13.4 Hz, 6H), 1.16 (t, / = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In lithium hydroxide monohydrate; toluene Reflux; Dean-Stark; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate for 0.5h; | 10D Example 10D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-l-carboxylate, hydrochloric acid A mixture of Example IOC (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HCl (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl (1033) acetate/heptane, and air-dried to give 11.3 g of title compound as an HCl salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
12.07 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In lithium hydroxide monohydrate; toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride; lithium hydroxide monohydrate In ethyl acetate | 68.68D Example 68D: ethyl 4-(benzylamino )-2-oxobicyclo[ 2.2.2 ] octane- 1-carboxylate, hydrochloric acid A mixture of Example 68C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /?-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C with Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, air-dried to give 11.3 g of title compound as an HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid. JH NMR (400 MHz, DMSO- |
11.3 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride In ethyl acetate for 0.5h; | 7.D; 174.D Example 7D: ethyl 4-(benzylamino )-2-oxobicyclo[ 2.2.2 ] octane- 1-carboxylate A mixture of Example 7C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /?-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HC1 (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl (0847) acetate/heptane, air-dried to give 11.3 g of title compound as a HC1 salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid. JH NMR (400 MHz, DMSO- |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate for 0.5h; | 13.13D Example 13D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylate, hydrochloric acid A mixture of Example 13C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HCl (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethylacetate/heptane, and air-dried to give 11.3 g of the title compound as an HCl salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL × 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound.1H NMR (400 MHz, DMSO-d6) d ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87- 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; Stage #2: With hydrogenchloride In ethyl acetate for 0.5h; | 13D Example 13D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylate, hydrochloric acid A mixture of Example 13C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HCl (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of the title compound as an HCl salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL × 2). The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
0.77 g | Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; benzylamine With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; Stage #2: With hydrogenchloride In ethyl acetate for 0.5h; | 13D Example 13D: ethyl 4-(benzylamino)-2-oxobicyclo[2.2.2]octane-1-carboxylate, hydrochloric acid A mixture of Example 13C (9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and p-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at reflux with a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of ethyl acetate (50 mL) and 3 N HCl (100 mL) for 30 minutes. The precipitate was collected by filtration, washed with mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of the title compound as an HCl salt. The filtrate was neutralized with 6 N NaOH and extracted with ethyl acetate (100 mL × 2). The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (t, J = 6.2 Hz, 2H), 7.87 - 7.12 (m, 5H), 4.09 (m, 4H), 2.88 (s, 2H), 2.08 (dt, J = 20.7, 13.4 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H); MS (ESI+) m/z 302.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / toluene / 130 °C / Dean-Stark 2.1: hydrogen; 20% palladium hydroxide-activated charcoal / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium hydroxide; methanol / 16 h / 20 °C 5.1: triethylamine; diphenyl phosphoryl azide / toluene / 2 h / 110 °C 5.2: 16 h / 20 °C | ||
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4: sodium hydroxide; methanol / 16 h / 20 °C 5: diphenyl phosphoryl azide; triethylamine / toluene / 2 h / Reflux | ||
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / water; toluene / 130 °C / Dean-Stark 2.1: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium hydroxide; methanol / 16 h / 20 °C 5.1: diphenyl phosphoryl azide; triethylamine / toluene / 2 h / 110 °C 5.2: 16 h |
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2.1: 20% palladium hydroxide-activated charcoal; hydrogen / tetrahydrofuran / 22 h / 50 °C / 2585.81 Torr 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4.1: sodium hydroxide; methanol / 16 h / 20 °C 5.1: diphenyl phosphoryl azide; triethylamine / toluene / 2 h / 110 °C 5.2: 16 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 2: water; sodium hydroxide / methanol / 24 h / 20 °C | ||
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / water; toluene / 130 °C / Dean-Stark 2: water; sodium hydroxide / methanol / 24 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / toluene / Dean-Stark; Reflux 1.2: 0.5 h 2.1: sodium hydroxide; methanol; water / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: ethyl 1-acetyl-4-oxocyclohexane-1-carboxylate; 4-methoxy-benzylamine With toluene-4-sulfonic acid In toluene at 130℃; Dean-Stark; Stage #2: With hydrogenchloride In water; ethyl acetate for 0.5h; Dean-Stark; | 214.214A Example 173D: ethyl 4-(benzylamino )-2-oxobicyclo[ 2.2.2 ] octane- 1 -carboxy late General procedure: A mixture of ethyl l-acetyl-4-oxocyclohexanecarboxylate (Example 173C, 9.7 g, 45.7 mmol), benzylamine (14.98 mL, 137 mmol), and /?-toluenesulfonic acid monohydrate (0.087 g, 0.457 mmol) in toluene (100 mL) was stirred at 130 °C in a Dean-Stark trap apparatus overnight. The mixture was concentrated, and the residue was stirred with a mixture of 50 mL of ethyl acetate and 100 mL of 3 N aqueous HC1 for 30 minutes. The precipitate was collected by filtration, washed with a mixture of ethyl acetate/heptane, and air-dried to give 11.3 g of the title compound as a hydrochloride salt. The filtrate was neutralized with 6 N aqueous NaOH and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel (0-70% ethyl acetate in heptane) to give another 0.77 g of the title compound as yellow solid.JH NMR (400 MHz, DMSO-+. |
Tags: 72653-21-5 synthesis path| 72653-21-5 SDS| 72653-21-5 COA| 72653-21-5 purity| 72653-21-5 application| 72653-21-5 NMR| 72653-21-5 COA| 72653-21-5 structure
[ 64229-88-5 ]
Ethyl 5,5-dimethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 412314-46-6 ]
Ethyl 2,4-dioxospiro[5.5]undecane-1-carboxylate
Similarity: 1.00
[ 36168-42-0 ]
Ethyl 4,4-dimethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 55443-01-1 ]
Ethyl 1-ethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 7251-30-1 ]
Ethyl 1-(2-ethoxy-2-oxoethyl)-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 843-59-4 ]
Diethyl 2,5-dioxobicyclo[2.2.2]octane-1,4-dicarboxylate
Similarity: 1.00
[ 412314-46-6 ]
Ethyl 2,4-dioxospiro[5.5]undecane-1-carboxylate
Similarity: 1.00
[ 36168-42-0 ]
Ethyl 4,4-dimethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 55443-01-1 ]
Ethyl 1-ethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 7251-30-1 ]
Ethyl 1-(2-ethoxy-2-oxoethyl)-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 64229-88-5 ]
Ethyl 5,5-dimethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 412314-46-6 ]
Ethyl 2,4-dioxospiro[5.5]undecane-1-carboxylate
Similarity: 1.00
[ 36168-42-0 ]
Ethyl 4,4-dimethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 55443-01-1 ]
Ethyl 1-ethyl-2-oxocyclohexanecarboxylate
Similarity: 1.00
[ 7251-30-1 ]
Ethyl 1-(2-ethoxy-2-oxoethyl)-2-oxocyclohexanecarboxylate
Similarity: 1.00
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :