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CAS No. : | 4296-15-5 | MDL No. : | MFCD07644549 |
Formula : | C3H7IO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SZCAORBAQHOJQI-UHFFFAOYSA-N |
M.W : | 185.99 | Pubchem ID : | 79136 |
Synonyms : |
|
Num. heavy atoms : | 5 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 30.58 |
TPSA : | 9.23 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.6 cm/s |
Log Po/w (iLOGP) : | 1.85 |
Log Po/w (XLOGP3) : | 1.18 |
Log Po/w (WLOGP) : | 1.07 |
Log Po/w (MLOGP) : | 1.16 |
Log Po/w (SILICOS-IT) : | 1.22 |
Consensus Log Po/w : | 1.29 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 3.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.6 |
Solubility : | 4.62 mg/ml ; 0.0249 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.97 |
Solubility : | 20.0 mg/ml ; 0.107 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.77 |
Solubility : | 3.17 mg/ml ; 0.0171 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.65 |
Signal Word: | Danger | Class: | 3,6.1 |
Precautionary Statements: | P210-P240-P241-P242-P243-P261-P264-P270-P271-P280-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P332+P313-P337+P313-P362-P370+P378-P403+P233-P403+P235-P405-P501 | UN#: | 1992 |
Hazard Statements: | H226-H301-H315-H319-H335 | Packing Group: | Ⅲ |
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 |
---|---|---|
In acetone; sodium iodide; | 62b') 2-Methoxyethyl iodide A solution of 10 ml (109 mmol) of <strong>[627-42-9]2-chloroethyl methyl ether</strong> in 205 ml of acetone is treated in portions with 80.1 g (534 mmol) of NaI, and the mixture is boiled under reflux for 20 h. Partitioning the reaction mixture between 2 portions of ether and saline, drying the organic phases with Na2 SO4 and evaporating them (RT, 300 mbar) affords the title compound: 1 H-NMR (200 MHz, CDCl3): 3.25 (t, J=7 Hz, 2H), 3.39 (s, 3H), 3.65 (t, J=7 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium iodide; In acetone; for 3h;Heating / reflux; | F1. 2-Methoxyethyl iodide; The crude <strong>[17178-10-8]2-methoxyethyl tosylate</strong> is dissolved in 1600 ml of acetone and NaI (300 g, 2 mol, 2 equiv) is added. The mixture is heated to reflux and the progress of the reaction is monitored by TLC (toluene-acetone, 9:1 ). After 3 h the mixture is cooled to room temperature and the solid is removed by filtration. The solvent is evaporated, the residue is taken up in dichloromethane (700 ml) and is washed with 10 % aqueous Na2S2O3 and water. The organic layer is dried and the solvent evaporated. The residue is distilled at reduced pressure to yield 108 g (58 %) of 2-methoxyethyl iodide. B. p. 34-36 0C at 30 mbar. |
58% | With sodium iodide; In acetonitrile; for 3h;Heating / reflux; | The crude <strong>[17178-10-8]2-methoxyethyl tosylate</strong> is dissolved in 1600 ml of acetone and NaI (300 g, 2 mol, 2 equiv) is added. The mixture is heated to reflux and the progress of the reaction is monitored by TLC (toluene-acetone, 9:1 ). After 3 h the mixture is cooled to room temperature and the solid is removed by filtration. The solvent is evaporated, the residue is taken up in dichloromethane (700 ml) and is washed with 10 % aqueous Na2S2O3 and water. The organic layer is dried and the solvent evaporated. The residue is distilled at reduced pressure to yield 108 g (58 %) of 2- methoxyethyl iodide. B. p. 34-36 0C at 30 mbar. |
58% | With sodium iodide; In acetone; for 3h;Heating / reflux; | The crude <strong>[17178-10-8]2-methoxyethyl tosylate</strong> is dissolved in 1600 ml of acetone and NaI (300 g, 2 mol, 2 equiv) is added. The mixture is heated to reflux and the progress of the reaction is monitored by TLC (toluene- acetone, 9:1 v:v). After 3 h the mixture is cooled to room temperature and the solid is removed by filtration. The solvent is evaporated, the residue is taken up in dichloromethane (700 ml) and is washed with 10 % aqueous Na2S2O3 and water. The organic iayer is dried and the solvent evaporated. The residue is distilled at reduced pressure to yield 108 g (58 %) of 2-methoxyethyi iodide. B. p. 34-36 0C at 30 mbar, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; for 3h;Heating / reflux; | 2-methoxyiodated ethane (32 g, 172 mmol) was then dispersed in THF (500 ml). To the dispersion thus obtained was then added hydrogenated sodium (60%, 6.4 g, 172 mmol). To the reaction mixture was then added dropwise a solution of M-19 (16.5 g, 71.7 mmol) in THF (50 ml) in an atmosphere of nitrogen. The reaction mixture was then heated under reflux for 3 hours. The reaction mixture was then cooled to room temperature. To the reaction mixture was then added water (60 ml). THF was then distilled off. The reaction solution was then extracted with methylene chloride. The resulting extract was dried over magnesium sulfate, and then concentrated. The material thus concentrated was then purified through silica gel column chromatography to obtain M-20 (8.3 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; for 3h;Heating / reflux; | 2-methoxyiodated ethane (1.54 g, 8.3 mmol) was then dispersed in THF (400 ml). To the dispersion thus obtained was then added hydrogenated sodium (60%, 0.31 g, 8.4 mmol). To the reaction mixture was then added M-21 (2.6 g, 6.9 mmol). To the reaction mixture was then added dropwise a solution of M-21 (2.6 g, 6.9 mmol) in THF (40 ml) in an atmosphere of nitrogen. The reaction mixture was then heated under reflux for 3 hours. The reaction mixture was then cooled to room temperature. To the reaction mixture was then added water (60 ml). THF was then distilled off. The reaction solution was then extracted with methylene chloride. The resulting extract was dried over magnesium sulfate, and then concentrated. The material thus concentrated was then purified through silica gel column chromatography to obtain M-22 (1.6 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In DMF (N,N-dimethyl-formamide); at 0℃; for 1.5h;4A molecular sieve; | 2-Methyl-propane-1-sulphonic acid 4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4'-hydroxy-biphenyl-2-yl ester (100 mg, 0.21 mmol) are [sic] initially introduced into 2.1 ml abs. dimethylformamide, 320 mg powdered molecular sieve 4A and, after 15 min, 43 mg (0.38 mmol) potassium tert-butylate are added and the mixture is stirred for a further 5 minutes. It is subsequently cooled to 0 C. and 55 mg (0.30 mol) 1-iodo-2-methoxy-ethane are then added. After 1.5 h at 0 C. the reaction mixture is diluted with a mixture of CH2Cl2/MeOH/25% NH3(90/10/1), filtered and evaporated and the crude product is purified by means of flash chromatography over SiO2 (CH2Cl2/MeOH/25% NH3(19/1/0.05). 70 mg of the title compound are obtained here as a colourless foam. [01334] MS (ISP): 531.3 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With sodium iodide; In acetone;Reflux; | Compound 2, was prepared according to the procedures illustrated in WO 2003/091227. Compound 1 (15 g, 0.11 mol, 1.0 eq, commercially available) was added to a solution of sodium iodide (22.5 g, 0.15 mol, 1.36 eq) in acetone (50 mL) and stirred overnight under reflux. The reaction mixture initially turned brown, then slowly changed to dark orange. The byproduct, sodium bromide, was observed as it crashed out as a white precipitate. After stirring for 12 h, the reaction mixture was poured into ice water (200 mL) and extracted with diethyl ether (3 x 100 mL). The combined organic layers were sequentially washed with saturated sodium thiosulfate (3 x 50 mL), water and brine then dried over MgS0 . The solution was filtered through a thin pad of Celite and silica gel and concentrated in vacuo to furnish 1 -iodo-2-methoxy-ethane, Compound 2 (13.31 g, 66%). To maximize shelf life, Compound 2 was stored in a freezer at -20 C under nitrogen |
64% | With sodium iodide; In acetone; for 3h;Heating / reflux; | To a solution of 1-bromo-2-methoxyethane (2.0 g, 14 mmol) in acetone (40 mL) was added sodium iodide (11 g, 72 mmol) and the resulting solution was refluxed (70 C.) under N2 for 3 hours. The mixture was cooled and filtered. Upon further cooling in the refrigerator, additional solids crashed out and were filtered off before concentrating to give an orange residue. The residue was taken up in ether and washed with Na2S2O3, which rendered a nearly colorless solution. The solution was dried (MgSO4), filtered, and concentrated to give a yellow oil (1.8g, 64%). 1H NMR (CDCl3) delta 3.70-3.60 (2H, t, J=5 Hz), 3.40 (3H, s), 3.30-3.20 (2H, t, J=5 Hz). |
With sodium iodide; In acetone; at 20℃; for 14h; | [1197] 10.4 g (75.0 mmol) of 1-bromo-2-methoxyethaneand 13.5 g(90.0mmol)ofsodiumiodidewerestirredin 75 mlof acetone at RT for 14 h. The solvent was then removed at 25 oC. and 220 mbar and the residue was taken up in 100 ml ofethyl acetate. The organic phase was twice washed with 50 mlof water, dried over sodium sulphate and filtered, and thesolvent was removed under reduced pressure. The crudeproduct was used for the next step without further purification.Yield: 12.5 g (90% of theory)[1198] GC/MS [Method 9]: Rt=1.56 min; MS: m/z=186(Mt[1199] 1H-NMR(400MHz, CDCI3 ): o [ppm]=3.66 (t, 2H),3.41 (s, 3H), 3.26 (t, 2H). |
12.5 g | With sodium iodide; In acetone; at 20℃; for 14h; | 10.4 g (75.0 mmol) of 1-bromo-2-methoxyethane and 13.5g (90.0 mmol) of sodium iodide were stirred in 75 ml of acetone at RT for 14 h.The solvent was then removed at 25 C and 220 mbar and the residue was taken upin 100 ml of ethyl acetate. The organic phase was twice washed with 50 ml ofwater, dried over sodium sulphate and filtered, and the solvent was removedunder reduced pressure. The crude product was used for the next step withoutfurther purification. Yield: 12.5 g Dm- 1.) I uiv rorelun LOUr1LrieS (90% of theory) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | To a 1.00 M solution of lithium hexamethyldisilazide in tetrahydrofuran (9.1 mL, 9.1 mmmol) under N2 at -78 C. was added a solution of methyl (1R,4S)-4-[(tert-butoxycarbonyl)amino]cyclopent-2-ene-1-carboxylate (1.0 g, 4.1 mmol) in tetrahydrofuran (2.0 mL). The resulted light brown solution was stirred at -78 C. for 30 min before adding a solution of 1-iodo-2-methoxyethane (0.93 g, 5.0 mmol) in tetrahydrofuran (2.0 mL). The mixture was stirred for an hour at -78 C. then kept in a freezer reading at -20 C. overnight. The reaction was quenched with saturated ammonium chloride. The layers were separated and the aqueous extracted with ether three times. The combined organics were then washed with brine, dried (magnesium sulfate), filtered and purified by flash chromatography (EtOAc/Hexane) to provide the desired product (0.28 g, 23%). LCMS calculated for C15H26NO5: (M+H) 300.2; found 300.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; lithium diisopropyl amide; In tetrahydrofuran; 1,2-dimethoxyethane; n-heptane; ethyl acetate; | a Crude 1-[2-(tert-butoxycarbonyl)-4-methoxybutyl]cyclopentanecarboxylic acid To a solution of commercially supplied lithium diisopropylamide (9.63 kg of a 2M solution in tetrahydrofuran/n-heptane/ethylbenzene, 23.7 mol) in 1,2-dimethoxyethane (25 L) at -10 C. under an atmosphere of N2 was added a solution of 1-(3-tert-butoxy-3-oxopropyl)cyclopentane carboxylic acid (EP274234B1-see Example 35) (2.5 kg, 10.3 mol) in 1,2-dimethoxyethane (12.5 L) with stirring over a period of 4 hours whilst maintaining the reaction temperature at -10 C. The header tank was washed with 1,2-dimethoxyethane (2.5 L) and this was added to the reaction. The reaction mixture was then allowed to stir at -10 C. for 1.75 hours. To the resultant solution was added a solution of 2-iodoethyl methyl ether (2.73 kg, 14.4 mol) in 1,2-dimethoxyethane (10 L) over a period of 1.75 hours. The reaction was then stirred at this temperature for 4 hours before warming to 20 C. over a period of 4 hours. After stirring at this temperature for 8 hours the reaction was quenched by the addition of aqueous ammonium chloride (25 L of a 2.8 M solution), ethyl acetate (12.5 L) was then added. Aqueous hydrochloric acid (10 L of 5 M solution) was then added with stirring to adjust the pH to between 2 and 3. The two phases were mixed and then separated. The organic phase was then extracted three times with aqueous potassium carbonate solution (0.3 M solution; 37.5 L, 12.5 L and then 6.25 L). To the combined aqueous phases was then added n-heptane (15.6 L), and aqueous hydrochloric acid (14.5 L of a 5 M solution) with stirring until the pH of the aqueous layer was between 2 and 3. The layers were then separated and the aqueous phase was extracted with n-heptane (15.6 L). The combined organic phases were then washed with saturated brine (3.1 L) and were then concentrated under vacuum to give the crude title compound (2.50 kg, 8.32 mol, 81% yield) as a solution in n-heptane (21.8 kg total solution weight). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N-methyl-acetamide; hexane; ethyl acetate; | PREPARATION 105 1-Bromo-3-(2-methoxyethoxy)benzene Anhydrous potassium carbonate (4.2 g, 30.4 mmol) was added to a stirred solution of 3-bromophenol (5.0 g, 28.9 mmol) in anhydrous dimethylformamide (100 ml). After 5 minutes, 1-iodo-2-methoxyethane (Annalen, 1967, 710, 59; 5.9 g, 31.8 mmol) was added and the reaction mixture stirred at room temperature for about 16 hours. At this point the mixture was heated at about 50 C. for approximately 72 hours, before 1-chloro-2-methoxyethane (1.8 ml, 19.8 mmol) was added and heating continued for a further 24 hours. The resulting mixture was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was further extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated to a red oil, which was purified by flash chromatography using hexane:ethyl acetate (3:1) as eluant, to furnish the title compound as a colourless oil (1.7 g, 25%). delta(CDCl3): 3.43 (s,3H), 3.74 (t,2H), 4.10 (t,2H), 6.87 (d,1H), 7.10 (m,3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.8% | In N-methyl-acetamide; ethyl acetate; | (a) To a suspension of 1-(4-pyridyl)-2,3-bis(hydroxy-methyl)-6,7-diethoxynaphthalene (7.0 g) in dry dimethylformamide (14 ml) is added 2-methoxyethyl iodide (7.35 g), and the mixture is stirred at 80 C. overnight. The mixture is allowed to cool, and thereto added ethyl acetate. The precipitated crystal is collected by filtration to give 4-[2,3-bis(hydroxymethyl)-6,7-diethoxy-1naphthyl]-N-(2-methoxyethyl)pyridinium iodide (8.50 g). Yield: 79.8% M.p. 174-1760C. (recrystallized from acetone) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | In N-methyl-acetamide; ethyl acetate; | Reference Example 10 To a solution of 1-(4-pyridyl)-2,3-bis(methoxycarbonyl)-6-hydroxy-7-methoxynaphthalene (17 g) in dimethylformamide (50 ml) is added gradually sodium hydride (60% dispersion-type) under ice-cooling, and the mixture is stirred at room temperature for 30 minutes. The mixture is cooled with ice, and thereto is added 2-methoxyethyl iodide (10.3 g). The mixture is stirred at room temperature for 2 hours, and heated to 80 C. One hour thereafter, the reaction solution is allowed to cool, and concentrated. The resulting residue is dissolved in ethyl acetate, washed with water, dried, and concentrated. The precipitated crystal is washed with diethyl ether to give 1-(4-pyridyl)-2,3-bis(methoxycarbonyl)-6-(2-methoxyethyloxy)-7-methoxynaphthalene (8.5 g). Yield: 43% M.p. 156-158 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26 mg (26.8%) | With sodium chloride; potassium carbonate; In hexane; dichloromethane; argon; ethyl acetate; N,N-dimethyl-formamide; | STR25 85 mg (0.20 mmol) of Compound 5 synthesised in Reference Example 4 was dissolved in 0.8 ml of anhydrous DMF. To this solution, 115 mg (0.83 mmol) of potassium carbonate and a solution of 125 mg (0.67 mmol) of 1-iodo-2-methoxyethane in 0.4 ml of DMF were added, and this reaction mixture was stirred in a stream of argon at room temperature for 2 hours. To this reaction mixture, 137 mg (0.99 mmol) of potassium carbonate and a solution of 127 mg (0.68 mmol) of 1-iodo-2-methoxyethane in 0.2 ml of DMF were added, and this reaction mixture was stirred for 3 hours and 10 minutes. The mixture was added to water, and was then extracted with ethyl acetate. The extract layer was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated. The residue was chromatographed on silica gel and eluted with a mixed solvent of dichloromethane and ethyl acetate (5:1). The eluent was concentrated, and was then rechromatographed on silica gel and eluted with a mixed solvent of hexane and ethyl acetate (1:1), whereby ethyl (E)-7-[4'-fluoro-5-(2-methoxyethoxy)-3-(propan-2-yl)-biphenyl-2-yl]-3,5-dihydroxy-6-heptenoate (Compound 9) was obtained in the form of a colorless oil in a yield of 26 mg (26.8%). 1 H-NMR (300 MHz, CDCl3) delta 1.18-1.33(m, 1H), 1.21(d, J=6.8 Hz, 3H), 1.22(d, J=6.8 Hz, 3H), 1.28(t, J=7.2 Hz, 3H), 1.39-1.50(m, 1H), 2.33-2.49(m, 2H), 2.83(s with fine coupling, 1H), 3.23(hept, J=6.8 Hz, 1H), 3.46(s, 3H), 3.61(s with fine coupling, 1H), 3.72-3.79(m, 2H), 4.04-4.22(m, 3H), 4.18(q, J=7.2 Hz, 2H), 4.28-4.39(m, 1H), 5.19(dd, J=16.1 and 6.3 Hz, 1H), 6.51(dd, J=16.1 and 1.2 Hz, 1H), 6.66(d, J=2.6 Hz, 1H), 6.90(d, J=2.6 Hz, 1H), 6.96-7.07(m, 2H), 7.16-7.29(m, 2H)ppm. IR (liquid film): 3464, 2968, 2932, 1734, 1602cm-1. Mass (m/z, %): 474 (M+, 100), 456 (67), 410 (42), 341 (39), 325 (38), 301 (51), 300 (36), 299 (44), 288 (35), 287 (34), 241 (40), 239 (35), 59 (94). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; | Tris-(beta-cyanoethyl)-2-methoxyethyl-phosphonium iodide 135.2 g (0.7 mole) of tris-(2-cyanoethyl)-phosphine are dissolved, under nitrogen, in 500 ml of boiling acetonitrile and then 130.2 g (0.7 mole) of 1-iodo-2-methoxyethane are added. The mixture is refluxed for 12 hours. After rapid filtration of the hot solution and cooling, the reaction product crystallises out and is collected by suction filtration and dried in vacuo at 60 C. Yield: 205.8 g (77.5% of theory). Melting point: 170-171 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; | EXAMPLE 7 beta-Cyanoethyl-2-methoxyethylphenylphosphine (formula 110) Bis-(beta-cyanoethyl-2-methoxyethyl-phenylphosphonium iodide 8.5 g (0.04 mole) of bis-(beta-cyanoethyl)-phenylphosphine are dissolved in 50 ml of absolute acetonitrile in a nitrogen atmosphere. Then 7.71 g (0.04 mole) of 1-iodo-2-methoxyethane are added and the mixture is refluxed for 12 hours. The solvent is distilled off to yield 13.2 g (82% of theory) of the product in the form of a solid, glassy substance. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In acetone; for 144h;Heating / reflux; | E2. 5-(2-Methoxy-ethoxy)-1 H-indole; To a solution of 5-hydroxy-indole (15.2 g, 114 mmol) in 250 ml of dry acetone 2-methoxyethyl iodide (15 ml, 141 mmol, 1.25 equiv) and anhydrous K2CO3 (46.7 g, 338 mmol, 3 equiv) are added and the mixture is refluxed. Additional amounts of 0.5 equiv of 2-methoxyethyl iodide and K2CO3 are added each day. After 6 days TLC (toluene-acetone, 9:1 ) indicates the absence of starting material. The solid is removed by filtration, and the solvent is evaporated. The residue is taken up in dichloromethane (800 ml) and the solution is washed with 2 M aqueous HCI, 10 % aqueous NaHCO3, and water. The organic layer is dried and concentrated. Column chromatography (toluene-acetone, 9:1 ) provides 5-(2- methoxy-ethoxy)-1 H-indole (18.8 g, 86%). M. p. 58-60 0C (from ethyl acetate-light petroleum). |
86% | With potassium carbonate; In acetone; for 144h;Heating / reflux; | To a solution of 5-hydroxy-indole (15.2 g, 114 mmol) in 250 ml of dry acetone 2-methoxyethyl iodide (15 ml, 141 mmol, 1.25 equiv) and anhydrous K2CO3 (46.7 g, 338 mmol, 3 equiv) are added and the mixture is refluxed. Additional amounts of 0.5 equiv of 2-methoxyethyl iodide and K2CO3 are added each day. After 6 days TLC (toluene-acetone, 9:1 ) indicates the absence of starting material. The solid is removed by filtration, and the solvent is evaporated. The residue is taken up in dichloromethane (800 ml) and the solution is washed with 2 M aqueous HCI, 10 % aqueous NaHCO3, and water. The organic layer is dried and concentrated. Column chromatography (toluene-acetone, 9:1 ) provides 5-(2-methoxy-ethoxy)-1 H-indole (18.8 g, 86%). M. p. 58-60 0C (from ethyl acetate-light petroleum). |
86% | With potassium carbonate; In acetone; for 144h;Heating / reflux; | To a solution of 5-hydroxy-indole (15.2 g, 114 mmol) in 250 ml of dry acetone 2-meihoxyethy. iodide (15 ml, 141 mmol, 1.25 equiv) and anhydrous K2CO3 (46.7 g, 338 mmol, 3 equiv) are added and the mixture is refluxed. Additional amounts of 0.5 equiv of 2-methoxyethyi iodide and K2CO3 are added each day. After 6 days TLC (toluene-acetone, 9:1 v:v) indicates the absence of starting material. The <n="80"/>solid is removed by filtration, and the solvent is evaporated. The residue is taken up in dichloromethane (800 ml) and the solution is washed with 2 M aqueous HCi1 10 % aqueous NaHCO3, and water. The organic layer is dried and concentrated. Column chromatography (toluene-acetone, 9:1 v:v) provides 5-(2-methoxy-ethoxy)~1 H-indole (18.8 g, 86%). M.p. 58-60 0C (from ethyl acetate-light petroleum). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Example 2; Alkylation of the Methylated Oxime of (+)-nopinone; 1.094 g of the methylated oxime 1 (6.55 mmol, 1 eq.) and 60 ml of anhydrous THF are introduced under an argon atmosphere into a Schlenck tube previously dried in an oven. After the reaction medium has been cooled to -70 C., 5 ml of a previously prepared solution of n-BuLi in hexane (c=1.44; 1.1 eq., 7.2 mmol) are added dropwise, the temperature being maintained at between -70 C. and -60 C. After stirring for 1 h at this temperature, 1.34 g of iodoethyl methyl ether (1.1 eq., 7.2 mmol), previously diluted in 20 ml of anhydrous THF, are introduced dropwise over 30 min via a dropping funnel, care being taken to keep the reaction mixture at -60 C. When the addition has ended, the temperature of the reaction medium is raised slowly to -20 C. The reaction medium is analyzed by TLC to ensure the complete disappearance of the starting material (eluent: petroleum ether/AcOEt 9/1). Saturated NH4Cl solution is then added and the reaction mixture is extracted with ethyl ether. The organic phases are recovered, washed successively with saturated NaHCO3 solution and then with saturated NaCl solution, dried over MgSO4 and filtered. After evaporation of the solvent, the residue (1.7 g) is purified by chromatography on silica gel (eluent: petroleum ether/AcOEt 9/1) to give 1.045 g of the alkylated compound 2 in the form of a colorless oil with a yield of 71%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 45 - 50℃; for 12h; | ExampIe-4; Preparation of Erlotinib Hydrocloride, polymorphic form-P :(i) Preparation of N-(3-ethynyIphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazoIinamine (Erlotinib base).For the preparation of Erlotinib base, the starting intermediate N-(3-ethynyl phenyl)-6,7- dihydroxy-4-quinazolinamine, is obtained from the process described in steps (i) to (v) of Example-(l) of PCT international publication No. WO 2007/060691.Into a clean and dry stainless steel reactor, are charged 250 Lts of dimethyl formamide, followed by 30 Kgs of potassium carbonate (anhydrous) and 10 Kgs of N-(3-ethynyl phenyl)-6,7-dihydroxy-4-quinazolinamine under nitrogen atmosphere. To this reaction mixture 14.0 Kgs of 2-Iodo ethyl methyl ether is added and maintained at 45-5O0C for about 12 hrs and the reaction is found to be completed by HPLC -Test. Then the reaction mass is cooled to room temperature and the mass is centrifuzed to remove the inorganic salt .To the collected filtrate, demineralized water is slowly added, under stirring below 35C, so that the product is crystallized out. Then the product is centrifuged and washed with water and the wet cake is dried to get 9.8 Kgs (69% by theory) of Erlotinib base as a brownish yellow coloured crystalline solid. Purity : 99.17% (by HPLC)Melting range: 151-153C | |
With potassium carbonate; In N,N-dimethyl-formamide; at 45 - 50℃; | (vi) Preparation of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine (Erlotinib base) of formula (1)Into a 2.0 L four necked round bottomed flask equipped with a mechanical stirrer, reflux condenser, thermometer socket, are charged dimethylformamide (1250 ml), anhydrous potassium carbonate (150 g), N-(3-ethynylphenyl)-6,7-hydroxy-4-quinazolinamine (50 g) obtained from the process described in step (v) above. To the reaction mixture, 2-iodo-ethylmethyl ether (70 g) was added in about 10-15 minutes. Then slowly raised the temperature to 45 and maintained for 12 hours at 45-50 C. and the reaction was found to be over by HPLC. Then cooled the reaction mass to 30-35 C. and filtered to remove the inorganic salt. Washed the cake with DMF. The solvent was removed by distillation under reduced pressure. Cooled the reaction mass to 30-35 C. and extracted the product by the addition of water and methylene chloride. The organic layer was separated and washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure to get the residue which was triturated with toluene and the product was obtained by filtration and dried to get crude erlotinib base (N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine) (42 g) (59.1% by theory) as a light yellow colored crystalline solid.Purity: 99% (by HPLC).Melting range: 151-153 C.; (vii) Recrystallization of Erlotinib BaseInto a 1.0 L four necked round bottomed flask equipped with a mechanical stirrer, reflux condenser and thermometer socket, are charged ethyl acetate (480 ml), Erlotinib base (40 g) obtained by the process described in step (vi) above and slowly raised the temperature to 75-80 C. to dissolve the base completely. Then activated carbon (6 g) was charged and maintained for 15-20 minutes. Filtered and washed the carbon cake with hot ethyl acetate. The combined filtrate and washings were cooled to 25-30 C. and then cooled further to 0-5 C. The reaction mass was maintained at 0-5 C. for 1 hour, filtered, washed with chilled ethyl acetate and dried to get 36 g of pure erlotinib base of formula (1) as light yellow colored crystalline solid.MR: 154-155 C.Purity: 99.65% (by HPLC).IR (KBr): 3250, 2927, 1619, 1576, 1502, 1428, 1332, 1255, 1217, 1153, 1130, 1094, 1066, 1032, 979, 940, 849, 770, 662, and 588 cm-1.1H NMR (300 MHz, DMSO-d6): 3.29 (s, 6H); 3.73 (t, 4H); 3.92 (s, 1H); 4.11-4.21 (m, 4H); 7.14 (s, 1H); 7.38-7.48 (m, 2H); 7.53-7.75 (dd, 1H); 7.86 (s, 1H); 8.37 (s, 1H); 8.84 (s, 1H); 11.44 (s, 1H).13C NMR (75 MHz, DMSO-d6): 58.37, 68.60, 69.17, 69.66, 69.90, 81.09, 82.91, 100.28, 105.02, 107.12, 121.77, 125.19, 127.42, 128.78, 129.03, 135.16, 137.16, 148.19, 149.12, 155.30, 157.70.Mass: 394 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Sodium hydride in the form of an [80%] dispersion in oil - 150- (0.27 g) is added to a solution of [LH-INDOLE-3-CARBOXYLIC] acid ethyl ester (1.0 g) in N, N-dimethylformamide (25 ml), and the mixture is stirred at room temperature for 30 minutes. 3- Methoxyethyl iodide (1.5 g) is then added and the reaction mixture is stirred first for one hour at [50] C. and then overnight at [80] C. The mixture is poured into ice-water (50 ml), the aqueous phase is extracted with dichloromethane, and the combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated. The crude product is purified by FC (100 g of silica gel, eluant gradient from C to D). The title compound (1.26 [G),] Rf (C, double track) =0.44, is obtained in the form of an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In tetrahydrofuran; water; at 20℃; | Intermediate 1c: 1-(2-methoxyethyl)piperidin-4-one Hydrated 4-piperidone hydrochloride (8.65 g), 1-iodo-2-methoxyethane (12.58 g), and K2CO3 (15.55 g) were dissolved in a mixture of tetrahydrofuran (80 mL) and water (80 mL), stirred at room temperature, and allowed to stand overnight for layer separation. The water layer was extracted once with chloroform. The organic phases were combined, washed once with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated in vacuo to give the title compound as an oil. | |
With potassium carbonate; In tetrahydrofuran; water; at 20℃; | Preparation of 1c: 1-(2-methoxyethyl)piperidin-4-one Hydrated 4- piperidone hydrochloride (8.65 g), CH3OCH2CH2l (12.58 g) and K2CO3 (15.55 g) were dissolved separately in a mixture of tetrahydrofuran (80 ml) and water (80 ml), stirred at room temperature and allowed to stand overnight for layer separation. The water layer was extracted once with chloroform. The organic phase were combined, washed once with saturated salt water, dried over anhydrous magnesium sulfate and filtered. Finally the filtrate was evaporated in vacuo to give an oily product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.3% | Compound 3, prepared as per the procedures illustrated in Example 13 (0.25 g, 0.52 mmol) was dried over P2O5 under reduced pressure and then dissolved in anhydrous DMF (2 mL) under an atmosphere of argon. NaH (0.06 g, 1.6 mmol, 60% dispersion in mineral oil) was added with stirring for 30 minutes followed by addition of l-iodo-2-methoxyethane (0.15 g, 1.60 mmol). After stirring for 3 hours at room temperature under an atmosphere of argon the reaction was quenched with methanol (0.2 mL), diluted with EtOAc (20 mL), washed with water (15 mL) and brine (15 mL) then dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (50% EtO in hexanes) to yield Compound 12 (0.18 g, 64.3%). ES MS mlz 539.2 [M + H] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 25 - 30℃; for 6h;Reflux; Heating; | Example-12 Preparation of 3,4-bis-(2-methoxy-ethoxy)-benzaldehyde 80.0 g (0.57 mol) of 3,4-dihydroxy benzaldehyde and 800.0 ml of acetone were charged into 2.0 L4 necked round bottom flask, connect to a mechanical stirrer, thermo meter socket and condenser at 25-30 C. Reaction mass was stirred for 20 min.324.0 g (1.74 mol) of 1-iodo-2-methoxy-ethane and 240.0 g (1.70 mol) of potassium carbonate were charged. Reaction mass was heated to reflux. Reaction mass temperature was maintained at reflux for 6 hours. Reaction mass temperature was cooled to 25-30 C. and inorganic solid was filtered. Acetone was completely distilled under vacuum at below 60 C. Remaining mass was diluted with 400.0 ml of DM water. Compound was extracted with 400.0 ml of ethyl acetate and organic layer was dried with sodiumsulphate. Ethyl acetate was completely distilled under vacuum and finally applied high vacuum at below 60 C. 69.20 g of crude product (Oil) was obtained (yield: 47.0% by theory). Spectral Data:FT-IR:3448.5, 2932.7,2889.4, 2825.0, 1685.8, 1586.2, 1508.8, 1437.7, 1276.1, 11988.9, 1125.6, 1050.2, 810.4, 743.4, 653.6, 588.1.MS: 255.4[M+1] |
Yield | Reaction Conditions | Operation in experiment |
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b) Preparation of Compound 5The conditions used in preparing Compound 5 was in part carried out using similar procedures to those reported in the literature (Sanghvi, Y. S.; Theodorakis, E. A. et al J. Org. Chem. 2002, 67, 7887-7889 alpha Nucleosides, Nucleotides and Nucleic Acids 2003, 22, 583-587).Compound 2 was prepared per the procedures illustrated in Example 1. Compound 4 (10 g, 0.024 mol, 1.0 eq) and tetrabutyl ammonium iodide or TBAI (2.66 g, 0.0072 mol, 0.3 eq) were dissolved in anhydrous DMF (600 mL) and the volume was reduced to 500 mL in vacuo at 50 C. The reaction mixture was cooled to -20 C with stirring under nitrogen and a solution of NaHMDS (70 mL, 1M NaHMDS in THF, 0.07 mol, 3 eq) was added dropwise at 2 mL/min. The stirring was continued for 10 min at -20 C followed by the addition of l-iodo-2-methoxy-ethane (13.17 g, 0.071 mol, 3 eq). The progress of the reaction was monitored by LCMS and additional NaHMDS and alkylating reagent were added until Compound 4 was completely consumed. After standing for 64 h at -20 C, the reaction was quenched with cold MeOH (10 mL) and was poured into a solution of crushed ice (200 g) and water (1 L). The reaction mixture was diluted with EtOAc (500 mL) followed by the addition of saturated brine solution (500 mL). The organic layer was collected after partitioning and the aqueous layer was extracted twice with EtOAc (2 x 250 mL). The combined organic layers were sequentially washed with water and brine then dried (MgS04), concentrated in vacuo and dried under high vacuum to furnish the crude, Compound 5 as an orange oil, which was used without any further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 18h;Inert atmosphere; | General procedure: To a mixture of the appropriate 4-quinolone derivative (1 mmol) and potassium carbonate (2.8 mmol) in dry DMF the appropriate alkyl iodide (1.5 mmol) was added under N2 atmosphere. The reaction mixture was heated at 90 C for 18 h, unless otherwise stated. After cooling to room temperature, the mixture was poured into ice-water. The resulting N-alkyl 4-quinolone was collected by filtration and recrystallized from the appropriate solvent or extracted with dichloromethane and purified by flash column chromatography eluting with dichloromethane/methanol (98:2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate; In acetone; at 20℃; for 24h;Inert atmosphere; | General procedure C: To a mechanically stirred solution of perfluorooctanesulfonamide (50.0 g, 0.1 mol) and anhydrous K2CO3 (28.0 g, 0.2 mol) in acetone (100 mL), was added 1-iodo-2-methoxyethane (38.0 g, 0.2 mol) under an argon atmosphere. The mixture was stirred at room temperature for 24 h. Then acetone was removed by rotary evaporation to give crude product. The crude product was purified by distillation under reduced pressure |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | d) Preparation of 2'-O-(2-methoxyethyl)-3'-O-(2-methylnaphthalene)-5'-(R)-methyl-3-N-(benzyloxymethyl)-5-methyluridine (Compound 9) Compound 8 (4.30 g, 8.07 mmol) was dried over P2O5 under reduced pressure and dissolved in anhydrous DMF (24 mL). The mixture was cooled to -20 C. To this was added NaH (0.48 g, 12.11 mmol, 60% dispersion in mineral oil) with stirring for 30 minutes followed by addition of 1-methoxy-2-iodoethane (2.25 g, 12.11 mmol). The reaction mixture was warmed up to 0 C. After stirring for 1.5 h at 0 C. the reaction mixture was cooled to -20 C. and additional NaH (0.48 g, 12.11 mmol, 60% dispersion in mineral oil) was added. Stirring was continued at -20 C. for 30 minutes and 1-methoxy-2-iodoethane (2.25 g, 12.11 mmol) was added. The reaction mixture was warmed to 0 C. and with stirring for an additional 1.5 h. The reaction was quenched with methanol (5 mL), diluted with EtOAc (100 mL), washed with water (100 mL) and brine (100 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with 5% methanol in CH2Cl2 to yield Compound 9 (2.95 g, 62%). ES MS m/z 591.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate; In acetonitrile; at 20℃; for 12h; | General procedure: Individual solutions of N-(trimethylsilyl)methyl-N-hexylamine (16mmol) in MeCN (100mL) containing K2CO3 (36mmol) and alkyl halide (20mmol of 1-hexyl bromide, 2-ethyl-1-hexyl iodide, and 2-methoxy-1-ethyl iodide, and ethyl 2-bromoacetate) were stirred for 12h at room temperature and concentrated in vacuo to give residues that were in vacuo to afford residues, which were subjected to column chromatography (EtOAc: Hex=1: 10) to yield 7 (85 %), 8 (62 %), 9 (68 %) and 11 (80 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tetrabutylammomium bromide; potassium hydroxide; In dichloromethane; at 30℃; for 5h; | After the compound 1o (700 mg, 1.68 mmol) was dissolved in dichloromethane (15 mL), potassium hydroxide (278 mg, 4.22 mmol) and tetrabutylammonium bromide (60 mg) were added thereto, and iodomethyl (0.525 mL, 8.435 mmol) was slowly added thereto at room temperature. This solution was stirred for 10 hours at 25 C. Cooling water was added to the reaction material, and the result was adjusted to pH 5 to 6 using a 2N aqueous hydrochloric acid solution. After the organic layer was separated and taken, the aqueous layer was extracted once with dichloromethane, and the organic layers were combined, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated using silica gel column chromatography (normal-hexane/ethyl acetate=4/1) to give a pure target compound 1z (574 mg, 79%). Step 1: Preparation of (S)-methyl 2-tert-butoxy-2-(4-(4-chlorophenyl)-1-(2-methoxyethyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate (78a) A target compound 78a (178 mg, 78%) was obtained by reacting the compound 1n (200 mg, 0.482 mmol) in the same manner as in Step 1 of Example 1, except that iodo-2-methoxyethane (269 mg, 0.964 mmol) and potassium hydroxide (159 mg, 2.41 mmol) was used instead of iodomethyl and the stirring was carried out for 5 hours at 30 C. 1H-NMR (300 MHz, CDCl3) delta 0.97 (s, 9H), 1.48 (s, 3H), 2.30 (s, 3H), 2.69 (s, 3H), 3.34 (s, 3H), 3.66 (s, 3H), 3.73 (t, J=5.74 Hz, 2H), 4.40 (t, J=5.75 Hz, 2H), 5.07 (s, 1H), 7.22 (s, 1H), 7.43 (m, 3H): MS (EI, m/e)=472 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | at -180 - 125℃; for 18h;Schlenk technique; | General procedure: Compound 4 and alkyl or alkoxy halides were mixed at room temperature in a 100 mL Schlenk tube. After the sample was cooled to 180 C, the tube was evacuated and filled with N2. The reaction mixture was heated at 125 C for 18 h. The residue was washed with diethyl ether and dried under vacuum for 4 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With caesium carbonate; In N,N-dimethyl-formamide; at 25℃; for 4h; | A mixture of 5-(5-(4-cyano-lH-indol-2-yl)-l-methyl-6-oxo-l,6-dihydropyridazin-3- yl)-2-(4-fluorophenyl)-N-methyl-6- N-methylmethylsulfonamido)benzofuran-3-carboxamide (50 mg, 0.08 mmol), l-iodo-2-methoxy ethane (29 mg, 0.16 mmol) and Cs2CO 3 (102 mg, 0.31 mmol) in DMF (1.5 ml) was stirred at RT for 4 h. Filtration through a pad of celite removed the solid. After being washed with ethyl acetate, the combined filtrate was concentrated in vacuo. The resulting residue was purified by preparative TLC (eluted with 5% MeOH / DCM) to provide 5-(5-(4-cyano- 1 -(2-methoxy ethyl)- 1 H-indol-2-yl)- 1 -methyl-6-oxo- 1 ,6-dihydropyridazin-3-yl)-2-(4-fluorophenyl)- N-methyl-6-( -methylmethylsulfonamido)benzofuran-3-carboxamide (17, 30 mg, yield: 56%). MS (M+H)+: 683. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 4h; | Example 18A mixture of 5-(5-(4-cyano-lH-indol-2-yl)-l-methyl-6-oxo-l,6-dihydropyridazin- 3-yl)-2-(4-fluorophenyl)-N-methyl-6-(^-methylmethylsulfonamido)benzofuran-3-carboxamide (50 mg, 0.08 mmol), l-iodo-2-methoxyethane (29 mg, 0.16 mmol) and CS2CO 3 (102 mg, 0.31 mmol) in DMF (1.5 ml) was stirred at RT for 4 h. Filtration through a pad of celite removed the solid. After being washed with ethyl acetate, the combined filtrate was concentrated in vacuo. The resulting residue was purified by preparative TLC (eluted with 5% MeOH / DCM) to provide 5 -(5 -(4-cyano-l -(2-methoxyethyl)- lH-indol-2-yl)- l-methyl-6-oxo- 1 ,6-dihydropyridazin- 3-yl)-2-(4-fluorophenyl)-N-methyl-6-CN-methylmethylsulfonamido)benzofuran-3-carboxamide (17, 30 mg, yield: 56%). MS (M+H)+: 683. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 60℃; for 24.5h; | a. 4-(4-bromophenyl)-1-(2-methoxyethyl)-1H-pyrazole To a mixture of 4-(4-bromophenyl)-1H-pyrazole (100 mg, 0.45 mmol) and K2CO3 (130 mg, 0.94 mmol) in DMF (1.4 mL) was added a solution of 1-iodo-2-methoxyethane (115 mg, 0.62 mmol) in DMF (0.3 mL), and the resulting mixture was stirred at rt for 20 h. Additional iodo-2-methoxyethane (30 mg, 0.36 mmol) in DMF (0.1 mL) was added at this point and the mixture heated at 60 C. for 4.5 h. The mixture was allowed to cool to rt and concentrated in vacuo. The residue was purified by Biotage column chromatography (SNAP 10 g column, cyclohexane/EtOAc 100/0->80/20) to give the title compound as a colourless oil (119 mg, 94%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 - 20℃; for 17h; | [1201] 10.2 g (46.1 mmol) oftert-butyl1,3-dithiane-2-carboxylateand 12.0 g (64.5 mmol) of 1-iodo-2-methoxyethanewere initially charged in 127 ml of dimethylformamide, themixture was cooled to oo C. and 6.21 g (55.3 mmol) ofpotassium tert-butoxide were added. The resulting reactionmixture was stirred at oo C. for 1 h and at RT for 16 h. Thereaction mixture was added to 1.51 of a 1:2 mixture of ice andsaturated aqueous ammonium chloride solution and extractedthree times with 300 ml of diethyl ether. The combinedorganic phases were dried over magnesium sulphate and filtered,and the solvent was removed under reduced pressure.The crude product was used for the next step without furtherpurification. Yield: 11.1 g (87% of theory)[1202] LC/MS [Method 1]: R,=l.14 min; MS (ESipos):m/z=177 (M-COO-tert-ButyJt[1203] 1H-NMR (400 MHz, DMSO-d6): o [ppm]=3.46 (t,2H), 3.19 (s, 3H), 3.13-3.06 (m, 2H), 2.78-2.72 (m, 2H), 2.15(t, 2H), 2.08-1.98 (m, lH), 1.75-1.64 (m, lH), 1.45 (s, 9H). | |
11.1 g | With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h; | 10.2 g (46.1 mmol) of tert-butyl1,3-dithiane-2-carboxylate and 12.0 g (64.5 mmol) of 1-iodo-2-methoxyethanewere initially charged in 127 ml of dimethylformamide, the mixture was cooledto 0 C and 6.21 g (55.3 mmol) of potassium tert-butoxide were added. Theresulting reaction mixture was stirred at 0 C for 1 h and at RT for 16 h. Thereaction mixture was added to 1.5 1 of a 1:2 mixture of ice and saturatedaqueous ammonium chloride solution and extracted three times with 300 ml ofdiethyl ether. The combined organic phases were dried over magnesium sulphateand filtered, and the solvent was removed under reduced pressure. The crudeproduct was used for the next step without further purification. Yield: 11.1 g(87% of theory) |
Tags: 4296-15-5 synthesis path| 4296-15-5 SDS| 4296-15-5 COA| 4296-15-5 purity| 4296-15-5 application| 4296-15-5 NMR| 4296-15-5 COA| 4296-15-5 structure
[ 104539-21-1 ]
1-Iodo-2-(2-methoxyethoxy)ethane
Similarity: 0.86
[ 62573-16-4 ]
2-(2-(2-Iodoethoxy)ethoxy)ethanol
Similarity: 0.86
[ 62573-16-4 ]
2-(2-(2-Iodoethoxy)ethoxy)ethanol
Similarity: 0.86
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P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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