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Structure of Trimethoxymethylsilane
CAS No.: 1185-55-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 1185-55-3 |
Formula : | C4H12O3Si |
M.W : | 136.22 |
SMILES Code : | C[Si](OC)(OC)OC |
MDL No. : | MFCD00008342 |
InChI Key : | BFXIKLCIZHOAAZ-UHFFFAOYSA-N |
Pubchem ID : | 14456 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H316-H320-H373-H336-H225 |
Precautionary Statements: | P260-P240-P210-P233-P243-P241-P242-P271-P264-P280-P370+P378-P314-P337+P313-P305+P351+P338-P303+P361+P353-P332+P313-P304+P340+P312-P403+P233-P403+P235-P405-P501 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅱ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 32.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
27.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.67 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.06 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.91 |
Solubility | 16.8 mg/ml ; 0.123 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.83 |
Solubility | 20.2 mg/ml ; 0.149 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.72 |
Solubility | 25.7 mg/ml ; 0.189 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.66 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.1 |
* 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 |
---|---|---|
62.8% | Comparative Example 2 A 1000-ml four necked glass flask equipped with a reflux condenser, thermometer and stirrer was purged with nitrogen. The flask was charged with 136.2 g (1.0 mol) of methyltrimethoxysilane, 372.8 g (2.0 mol) of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane and 96.0 g (2.0 mol) of methanol, and cooled in an ice water bath to an internal temperature below 10C. To the flask kept at an internal temperature of 5-10C, 9.8 g (0.1 mol) of conc. sulfuric acid was added dropwise over 15 minutes, and stirring was continued at the temperature for 30 minutes. Subsequently, at a temperature of 5-25C, 105.0 g (5.83 mol) of water was added dropwise over one hour. After the completion of dropwise addition, stirring was continued at 15-25C for 2.5 hours. The aqueous layer was removed from the reaction solution, after which the organic layer was washed with aqueous sodium bicarbonate and then with water. On distillation of the resulting organic layer, 217.0 g (0.63 mol) of methyltris(trimethylsiloxy)silane with a purity of 99.7% was collected as a fraction having a boiling point of 102.0-103.0C/1.3 kPa. The yield was 62.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.4% | Example 7 A 1000-ml four necked glass flask equipped with a reflux condenser, thermometer and stirrer was purged with nitrogen. The flask was charged with 372.8 g (2.0 mol) of 1,3-divinyl-1,1,3,3-tetramethyldisiloxane and 64.0 g (2.0 mol) of methanol, and cooled in an ice water bath to an internal temperature below 10C. To the flask kept at an internal temperature of 5-10C, 9.8 g (0.1 mol) of conc. sulfuric acid was added dropwise over 30 minutes, and stirring was continued at the temperature for 30 minutes. Subsequently, to the flask kept at an internal temperature of 5-10C, 136.2 g (1.0 mol) of methyltrimethoxysilane was added dropwise over 30 minutes, and stirring was continued at the temperature for one hour. At an internal temperature of 5-25C, 105.0 g (5.8 mol) of water was added dropwise over one hour. After the completion of dropwise addition, stirring was continued at 15-25C for 2.5 hours. The organic layer of the reaction solution was analyzed by GC, finding that the area percent ratio of the main product to monomethoxy and monohydroxy compounds, MeSi (OSiMe2Vi)3/ [MeSi(OMe) (OSiMe2Vi)2 + MeSi(OH)(OSiMe2Vi)2] was 13.2. The total content of monomethoxy and monohydroxy compounds was 0.074 mol, as determined from the area percents by GC. The reaction solution was subjected to separatory operation to remove the aqueous layer. While the organic layer was kept at a temperature of 20-25C, 34.3 g (0.35 mol) of conc. sulfuric acid was added dropwise over 15 minutes, and stirring was continued at the temperature for 0.5 hour. The organic layer after reaction with sulfuric acid was analyzed by GC, finding that the area percent ratio of the main product to monomethoxy and monohydroxy compounds, MeSi (OSiMe2Vi)3/[MeSi(OMe) (OSiMe2Vi)2 + MeSi(OH)(OSiMe2Vi) 2] was 2990.7. The sulfuric acid layer was removed from the reaction solution, after which the organic layer was washed with water, neutralized with aqueous sodium bicarbonate, and washed with water again. On distillation of the resulting organic layer, 275.3 g (0.79 mol) of methyltris(dimethylvinylsiloxy)silane with a purity of 99.7% was collected as a fraction having a boiling point of 95.0-96.5C/0.9 kPa. The yield was 79.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 23℃; for 24h; | Diphenylsilanediol (60 g), tetrahydrofuran (THF, 30 g) and methyltrimethoxysilane (MTMOS, 180 g) were placed in a 500 mL 3-neck round bottom flask with a stir bar and reflux condenser. The reaction was allowed to proceed without ammonia catalyst for 24 hours at +23C. GC/MS showed that no desired reaction had taken place. Only some alkoxy/OH exchange between silanediol and MTMOS had occurred, to give methoxydiphenylsilanol and dimethoxydiphenylsilane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In tetrahydrofuran; at -20℃; for 5h; | Diphenylsilanediol (60 g), tetrahydrofuran (THF, 30 g) and methyltrimethoxysilane (MTMOS, 180 g) were placed in a 500 mL 3-neck round bottom flask with a stir bar and reflux condenser. The flask was cooled to -20C. l,8-Diazabicycloundec-7-ene (DBU, 0.5 g) was added into the solution. The reaction was allowed to proceed for 5 hours at -20C, after which GC/MS was run from the reaction mixture. It showed, that while low yields of the desired product was formed, over 80% of diphenylsilanediol was converted to dimethoxydiphenylsilane. DBU (pKb = 1.1) was clearly too strong base for this reaction and caused excessive side reactions |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.6% | Into a four-necked flask, 12 g of magnesium powder (0.5mol), 18 g of tetrahydrofuran (0.25mol), methyltrimethoxysilane 9.5G (0.07mol), chlorobenzene 3.4 g (0.03mol); was stirred and heated to reflux to start the reaction. Under reflux for about 1 hourSolution containing 90.1 g (0.8mol) of chlorobenzene, 29.9 g (0.2mol) methyl trichlorosilane and 177 g (1.3mol) methyltrimethoxysilane A mixed solution of methoxysilane; refluxing continued for 6.5h; cooled to room temperature, suction filtered, washed with an appropriate amount of methyltrimethoxysilane cakeTwice the combined filtrate is the crude product. By gas chromatographic analysis, the yield of methyl phenyl dimethoxysilane was 85.5percent (magnesiumCalculation). The crude product was distilled at atmospheric pressure to recover unreacted material, a vacuum distillation to give the product methylphenyl dimethoxysilane, purity99.6percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 15-crown-5; sodium; at 38℃; for 2h; | Sodium metal particles suspension was added to a mixture of 62.5 g of chlorobenzene and 227 g of methyltrimethoxysilane, and then 0.32 g of 15-crown-5 was added. The reaction was carried out at 38 ° C for 2 h , The reaction was stopped, and the reaction mixture was filtered and vacuum-distilled to give methylphenyldimethoxysilane in a yield of 87percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium; at 38℃; for 2h; | A suspension of sodium metal particles was added to a mixture of 87. 22 g of bromobenzene and 227 g of methyltrimethoxysilane,Then added0.32 g of cyclodextrin,The reaction was stopped at 38 ° C for 2 h, and the reaction mixture was filtered and reduced in vacuum to give methylphenyldimethoxysilane in a yield of 80percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31%; 17% | In tetrahydrofuran; for 1h; | (This example, as a comparative example, does not include the addition of 241 g of methyltrimethoxysilane and 1000 mL of tetrahydrofuran in a 5 L four-necked bottle within the scope of the present invention, starting with stirring, dropping 1030 mL of 1.72 mol / L Chlorophenyl Grignard reagent in tetrahydrofuran After 1 hour of reaction, most of the tetrahydrofuran was distilled off and 1000 mL of xylene was added and the remaining tetrahydrofuran was distilled off and allowed to cool to room temperature and filtered to give 99 g of phenylmethyldi Methoxysilane (yield 31percent) and 69 g of diphenylmethylmethoxysilane (yield 17percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In diethyl ether; for 1h;Reflux; | 5L four-necked flask by adding 240g methyltrimethoxysilane and 1000mL ether, stirring drop 1080mL 1.63mol / L bromobenzene reagent ether solution; drop Bi, heated reflux 1h .; cooling, to the reaction (Yield 95percent) of phenylmethyldimethoxysilane and 4 g of diphenylmethoxysilane (yield 1percent) were added to the filtrate by adding 1000 mL of n-hexane and then filtering. |