Structure of 5817-70-9
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| CAS No. : | 5817-70-9 |
| Formula : | C9H11NO2 |
| M.W : | 165.19 |
| SMILES Code : | O=C(OC)NCC1=CC=CC=C1 |
| English Name : | Methyl benzylcarbamate |
| MDL No. : | MFCD00025856 |
| InChI Key : | ZWZIHLRSOOMEKT-UHFFFAOYSA-N |
| Pubchem ID : | 232620 |
| Num. heavy atoms | 12 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.22 |
| Num. rotatable bonds | 4 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 45.5 |
| TPSA ? Topological Polar Surface Area: Calculated from |
38.33 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.07 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.35 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.39 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.51 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.25 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.51 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.82 |
| Solubility | 2.5 mg/ml ; 0.0151 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-1.76 |
| Solubility | 2.89 mg/ml ; 0.0175 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.92 |
| Solubility | 0.198 mg/ml ; 0.0012 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 |
Yes |
| 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) |
Yes |
| 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 |
-6.35 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 |
1.0 |
| 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 |
0.0 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) |
1.07 |
* 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 |
|---|---|---|
| 100% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; mercury(II) diacetate In N,N-dimethyl-formamide for 12h; Ambient temperature; | |
| 100% | Stage #1: Benzeneacetamide With 2,3,4,5,6-pentamethyliodobenzene; oxygen; isobutyraldehyde In 1,2-dichloro-ethane at 40℃; for 3h; Stage #2: methanol In 1,2-dichloro-ethane for 24h; | |
| 97% | With iodobenzene; Oxone at 20℃; |
| 96% | With Oxone; iodobenzene In water at 40℃; for 5h; Inert atmosphere; | |
| 95% | With N-Bromosuccinimide; 1,8-diazabicyclo[5.4.0]undec-7-ene for 0.416667h; Heating; | |
| 95% | With N-Bromosuccinimide; 1,8-diazabicyclo[5.4.0]undec-7-ene for 0.75h; Reflux; | |
| 94% | With sodium bromide In acetonitrile at 50℃; for 6h; Electrochemical reaction; Green chemistry; | |
| 91% | With iodosobenzene In dichloromethane at 20℃; for 2h; | |
| 84% | Stage #1: Benzeneacetamide With trichloroisocyanuric acid; 1,8-diazabicyclo[5.4.0]undec-7-ene at 20℃; Inert atmosphere; Stage #2: methanol at 65℃; Inert atmosphere; | |
| 82% | With lithium hydroxide monohydrate; N-bromoacetamide at 0 - 25℃; for 24h; Darkness; | Cyclic Ureas and Carbamates 2; General Procedure General procedure: To a solution of a carboxamide 1 (0.6-7 mmol) in MeOH (0.2-0.9 M) was added LiOH·H2O (2-15 equiv), with the flask protected from light and cooled to 0 °C with stirring. Solid NBA (1-8 equiv) was added in one portion and the heterogeneous mixture was stirred, while the temperature gradually attained r.t. The reaction progress was monitored by TLC, requiring 24-48 h for completion. The reaction mixture was added to 10% aqueous Na2S2O5 (2 volumes) and concentrated on a rotary evaporator (30 °C, 30 min). The liquid residue was diluted with 5% aqueous NaOH (15 volumes) and extracted with CH2Cl2 (3 × 8 volumes). The combined extracts were concentrated on a rotary evaporator and vacuum-dried (0.2 mmHg, 40 °C, 1 h). Further purification, when necessary, was achieved by dry-column flash chromatography, using the solvent gradient as indicated. When BnOH was used instead of MeOH, the procedure was modified as follows: After reaction completion, the mixture was diluted with CH2Cl2(25 volumes) and extracted successively with 10% aqueous Na2S2O5 (2 volumes) and 5% aqueous NaOH (15 volumes). The organic layer was concentrated on a rotary evaporator and the excess BnOH was removed under reduced pressure (0.2 mm Hg, 80 °C, 45 min). When necessary, the product was purified by dry-column flash chromatography. |
| 79% | With tetraethylammonium bromide In acetonitrile Ambient temperature; electrochemically induced (Pt electrodes, 100 mA); | |
| 79% | With aluminum oxide; potassium fluoride; sodium hypochlorite In water for 0.5h; Heating; | |
| 69% | With 3-methyl-2-[hydroxy(tosyloxy)iodo]benzoic acid for 8h; Inert atmosphere; Reflux; | |
| With lead(IV) acetate | ||
| 61 % Chromat. | With potassium bromide electrolysis with platinum electrodes; | |
| With sodium bromide In acetonitrile Electric arc; | ||
| With lithium hydroxide monohydrate; N-bromoacetamide at 65℃; Darkness; | General procedure for the synthesis of carbamates 1-5 General procedure: To a magnetically stirred solution of corresponding carboxamide (3.7 mmol, 1.0 equiv.)in MeOH (5 mL), LiOH·H2O (5.0 equiv.) and NBA (1.5 equiv.) were added. The mixture wasallowed to steer at 65 °C, in dark. Reaction was monitored by TLC, on SiO2 plates, using themixture of n-hexane/EtOAc = 1:1 and CH2Cl2/MeOH = 9:1, as eluent. After 5 min, the mixturewas concentrated by rotary evaporator to give a residue which was mixed with 1 M solutionof NaOH (20 mL). The mixture was extracted with 2×25 mL of CH2Cl2. The organiclayers were combined and concentrated by rotary evaporator. The obtained crude product waspurified by dry-column flash chromatography (SiO2; petroleum ether/EtOAc, 8:2 to 1:1). Thespectroscopic data for compounds 1-5 are given in Supplementary material to this paper andare in accordance with the previously published data | |
| 89 % | Stage #1: Benzeneacetamide With Oxone; potassium chloride In water; acetonitrile at 0 - 20℃; Stage #2: methanol With caesium carbonate | |
| 74 % | With sodium bromide In acetonitrile at 40℃; Electrochemical reaction; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | In dichloromethane for 1h; | |
| 94% | ||
| 91% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; |
| 87% | With potassium carbonate In acetone Heating; | |
| 86% | With indium In acetonitrile at 20℃; for 8h; Inert atmosphere; | |
| With bis-(trimethylsilyl)acetamide 1.) CH2Cl2, 20 deg C, 1 h, 2.) 0 -> 20 deg C, 1 h: 20 deg C, 1 h; Yield given. Multistep reaction; | ||
| With sodium hydroxide; water | ||
| With pyridine In dichloromethane at 20℃; for 1h; | ||
| With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; | ||
| With triethylamine In ethyl acetate | ||
| With triethylamine In dichloromethane at 0 - 20℃; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 59% | With 1,10-Phenanthroline; copper(ll) sulfate pentahydrate; potassium phosphate monohydrate In toluene at 100℃; for 48h; Inert atmosphere; | |
| 50% | Stage #1: methyl N-benzylcarbamate With pyridine; copper(l) iodide; potassium hexamethylsilazane In tetrahydrofuran at 20℃; for 2h; Stage #2: 1-bromo-1-octyne In tetrahydrofuran; benzene at 20℃; for 20h; | |
| 42% | With potassium phosphate; N,N`-dimethylethylenediamine In toluene at 150℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | Stage #1: methyl N-benzylcarbamate With pyridine; copper(l) iodide; potassium hexamethylsilazane In tetrahydrofuran at 20℃; for 2h; Stage #2: 1-bromo-2-(triisopropylsilyl)acetylene In tetrahydrofuran; benzene at 20℃; for 20h; | |
| 36% | With potassium phosphate; N,N`-dimethylethylenediamine In toluene at 110℃; | |
| 12% | With 1,10-Phenanthroline; copper(ll) sulfate pentahydrate; potassium carbonate In toluene at 85℃; for 48h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | at 20℃; for 16h; neat (no solvent); | |
| 99% | In toluene at 70℃; for 15h; | 5 Example 5 Synthesis of benzylmonomethyl carbamate In a vessel made of glass having an internal volume of about 19 ml and being equipped with a stirring device, a thermometer and a condenser were charged 500 mg (4.67 mmol) of benzylamine, 2.36 g (28.00 mmol) of dimethyl carbonate, 5 mL of toluene, and 25 mg of lipase from Candida Antarctica (Novozym 435 (trade name), manufactured by Novozymes) and mixed, and the mixture was reacted under stirring at 70° C. for 15 hours. After completion of the reaction, the reaction solution was filtered, and the filtrate was washed with toluene. The filtrate solution was concentrated to obtain 763 mg of benzylmonomethyl carbamate in the form of a pale yellow liquid (yield of the isolated product, based on benzylamine: 99%). |
| 96% | With tetrabutylammomium bromide; <i>L</i>-proline at 20℃; for 3h; Green chemistry; |
| 95% | With ytterbium(III) triflate at 80℃; for 8h; | |
| 94% | With aminosulfonic acid at 100℃; for 8h; | |
| 93% | With 8Na(1+)*12C4H10NO(1-)*2HO(1-)*2Nd(3+) In neat (no solvent) at 80℃; for 12h; Inert atmosphere; Schlenk technique; Green chemistry; | |
| 89% | With [(Me3Si)2N]3La(μ-Cl)Li(THF)3 In neat (no solvent) at 80℃; for 12h; Glovebox; | |
| 88% | With 2-hydroxypyridin; zirconium(IV) tert-butoxide at 80℃; for 12h; | |
| 83% | With scandium tris(trifluoromethanesulfonate) at 20℃; for 24h; | |
| 80% | With sodium methylate In methanol Heating; | |
| 13 % Chromat. | With scandium tris(trifluoromethanesulfonate) In tetrahydrofuran at 19.85℃; for 24h; | |
| With potassium <i>tert</i>-butylate at 90℃; for 0.0166667h; | ||
| In methanol at 19.84℃; | ||
| at 19.84℃; for 21h; | ||
| With 3-amino-1,2,4-triazole potassium at 80℃; for 10h; | ||
| 1.6 g | With binder-free FeHY-mmm zeolite In neat (no solvent) at 120℃; for 1h; Sealed tube; | General procedure for the methoxycarbonylation of alkyl-, cycloalkyl-, and arylamines with dimethyl carbonate. General procedure: The reactions were carried out in a 17-mL stainless steel high-pressure micro reactor or a 20-mL glass ampule. The results of parallel runs were almost the same. The reactor (ampule) was charged with 3-5 wt % of FeHY-mmm, 10 mmol of the corresponding amine, and 40 mmol of dimethyl carbonate. The reactor was hermetically closed (the ampule was sealed) and heated at 120°C for 0.5-2 h. When the reaction was complete, the reactor (ampule) was cooled to room temperature and opened, the mixture was filtered through a layer of alumina, excess dimethyl carbonate was distilled off, and the residue was distilled under atmospheric or reduced pressure or crystallized from ethanol. |
| With silica sulfuric acid at 90℃; Molecular sieve; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | With potassium phosphate; 1,10-Phenanthroline; copper(II) sulfate In toluene at 65 - 76℃; for 32h; | |
| 73% | With potassium phosphate; 1,10-Phenanthroline; copper (II) sulfite In toluene at 60 - 65℃; | |
| 72% | With 1,10-Phenanthroline; copper(ll) sulfate pentahydrate; potassium phosphate monohydrate In toluene at 100℃; for 48h; Inert atmosphere; |
| 63% | Stage #1: methyl N-benzylcarbamate With pyridine; potassium hexamethylsilazane In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: With copper(l) iodide In tetrahydrofuran at 20℃; for 2h; Stage #3: 1-Bromo-2-phenylacetylene In tetrahydrofuran at 20℃; for 20.75h; Darkness; | |
| 61% | With potassium hexamethylsilazane In toluene at 90℃; for 12h; | |
| 61% | With copper(l) iodide; 1,10-Phenanthroline; potassium hexamethylsilazane In toluene at 90℃; for 16h; | |
| 60% | With 1,10-Phenanthroline; copper(ll) sulfate pentahydrate; potassium carbonate In toluene at 80℃; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With acetic anhydride; periodic acid In acetonitrile at -10℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine In 1,4-dioxane at 60℃; for 24h; Inert atmosphere; regioselective reaction; | |
| 67% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With toluene-4-sulfonic acid In chloroform at 65℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 12 mg | In dichloromethane at 20℃; for 4.5h; Inert atmosphere; | |
| 150 mg | With triethylamine In dichloromethane at 20℃; for 1h; Inert atmosphere; | 1. General procedure of the one-pot synthesis of carbamates General procedure: Boc-protected amine 1(1.0 mmol) and 2-Cl-pyridine (3.0mmol) were dissolved in dry dichloromethane (0.05 M). Tf2O (1.5mmol) was added dropwise over 5 min. After stirring for 1 hour at room temperature, alcohol 5(3.0 mmol) and triethylamine (3.0 mmol) were added to the resulting mixture. After additional stirring for 1 hour, the mixture was diluted with dichloromethane and water, the mixture was extracted with dichloromethane (3 x10 mL) and the combined organic layer was washed with brine and water, dried over MgSO4, filtered and concentrated under reduced pressure. Purification by flash chromatography with EtOAc/hexane afforded the corresponding carbamates. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 59% | With tetrachloromethane; boron trifluoride diethyl etherate In 1,2-dichloro-ethane at 20℃; for 4h; Inert atmosphere; | General procedure: synthesis of methyl (R)-2-[(10-hydroxy-3-oxo-3,10b-dihydro-1H-oxazolo[4,3-a]isoquinolin-5-yl)methyl](methyl)amino}acetate (10) (Scheme 2) General procedure: SiCl4 (0.03 mL, 0.27 mmol) and BF3·Et2O (0.004 mL, 0.03 mmol) were added to a stirred solution of 9 (20.4 mg, 0.05 mmol) in 1,2-DCE (2 mL) under argon at room temperature. After stirring for 4 h, Et3N (0.3 mL) and EtOH (2 mL) were added. An insoluble residue was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography over silica gel with n-hexane-EtOAc (1:1) to give 10 as a white solid (14.5 mg, 84% yield). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | Stage #1: methyl N-benzylcarbamate With 3-azapentane-1,5-diamine at 140℃; for 12h; Sealed tube; Stage #2: With hydrogenchloride In diethyl ether at 0 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 71% | With molybdenum(VI) oxide at 160℃; for 0.2h; Autoclave; | 10 Example 10 0.5 mmol of phenylmethylamine, 0.015 mmol of MoO3, 0.0025 mmol of FeOx/C (loading amount of 0.2 wt%), and 20 mmol of methanol were added to a 20 mL PTFE-lined stainless steel reactor and charged with 2 MPa of air. Heat to 160°C and react at this temperature for 0.2 h. The mixture was suction filtered, the solvent was removed by rotary evaporation, 5 mL of H2O was added, and the mixture was extracted with ethanol-ethyl acetate to obtain highly pure N-phenyl, N-methyl-carbamic acid methyl ester in an isolated yield of 71%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 1.02 g 2: 1.16 g | With sodium hydroxide at 80℃; for 12h; Schlenk technique; Sealed tube; | 2 The crude product of the first step reaction was dissolved in ethanol (20 mL), transferred to a Schlenk reaction bottle, and a catalytic equivalent of sodium hydroxide (80 mg, 2 mmol) was added, and then sealed. The temperature was raised to 80°C for reaction for 12 hours. After cooling to room temperature, the bottle stopper was opened, biphenyl was added as an internal standard, and then sampling was performed to monitor the reaction. By gas chromatography (using biphenyl as an internal standard to make a standard curve), it was found that the content of the target product methyl ethyl carbonate in the reaction solution was 1.02 g (9.8 mmol), and the total yield of the two steps was 49%; the content of benzylamine was 1.16 g (10.8 mmol), and the total yield of the two steps was 54%. |

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