Structure of 10421-85-9
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CAS No. : | 10421-85-9 |
Formula : | C8H7ClO3 |
M.W : | 186.59 |
SMILES Code : | C1=C(C(C(O)=O)O)C(=CC=C1)Cl |
MDL No. : | MFCD00084962 |
InChI Key : | RWOLDZZTBNYTMS-UHFFFAOYSA-N |
Pubchem ID : | 97720 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 44.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
57.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.13 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.26 |
Solubility | 1.04 mg/ml ; 0.00555 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.44 |
Solubility | 0.677 mg/ml ; 0.00363 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.86 |
Solubility | 2.56 mg/ml ; 0.0137 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) |
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 |
-6.29 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 |
0.56 |
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) |
1.98 |
* 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 |
---|---|---|
97% | With sulfuric acid; at 60℃; | General procedure: A few drops of conc. H2SO4 were added to a stirred solution of mandelic acid 6a (4.56 g, 29 mmol) in methanol (50 ml). The reaction was refluxed for 3 hours, after which the solvent was removed and the residue dissolved in ethyl acetate (25 ml). The product was washed with a 10% aqueous K2CO3 solution (2 x 50 ml) and then with brine (2 x 50 ml). The organic layer was dried (MgSO4) and reduced to give the title compound as a white crystalline solid, |
With hydrogenchloride; In water; at 75℃; for 3.0h; | Example 1. Preparing of racemic alkyl 2-chloromandelate[30][31] 2g of racemic <strong>[10421-85-9]2-chloromandelic acid</strong> was added to 40ml of methanol and 35 % HCl solution. The reaction was carried out at 75 0C for 3 hours. The reaction mixture was neutralized and racemic methyl 2-chloromandelate was gained by solvent extraction and distillation under reduced pressure. Racemic ethyl 2-chloromandelate and butyl <n="5"/>2-chloromandelate were synthesized using ethanol or buthanol, respectively instead of methanol. And the products were confirmed by nuclear magnetic resonance(Burker, Model DRS300).[32] Methyl 2-chloromandelate [33] 1H-NMR(CDCl , 300MHz) delta(ppm) = 3.76(s, 3H), 5.57(s, IH), 7.27(m, 2H), 7.39(m, 2H)[34] Ethyl 2-chloromandelate [35] 1H-NMR(CDCl , 300MHz) delta(ppm) = 1.21(t, 3H), 4.21(m, 2H), 5.54(s, IH), 7.27(m, 2H), 7.38(m, 2H)[36] Butyl 2-chloromandelate [37] 1H-NMR(CDCl , 300MHz) delta(ppm) = 0.83(t, 3H), 1.23(m, 2H), 1.54(m, 2H), 4.16(t, 2H), 5.56(s, IH), 7.25(m, 2H), 7.38(m, 2H) | |
With sulfuric acid; magnesium sulfate;Reflux; | To a stirring solution of 1000 g racemic o-chloromandelic acid dissolved in 1 L methanol were added 120 g MgSO4 and 10 ml H2SO4. The mixture was refluxed with agitation until o-chloromandelic acid was completely consumed (as monitored by TLC). After cooled to room temperature, MgSO4, and methanol were removed by filtration and rotary evaporation. Then the mixture was neutralized by saturated Na2CO3 solution and dried over anhydrous Na2SO4 to give racemic CMM. To a stirring solution of 800 g CMM dissolved in 2 L CH2Cl2 and pre-cooled at 0-10oC was added Jones reagent which was prepared by adding grinded Cr2O3 powder (530 g) into stirring concentrated H2SO4 (460 ml) followed by diluting with water to 2 L. The progress of the reaction was monitored by TLC analysis till the reaction was completed. The organic layer was separated and washed with saturated Na2CO3 solution, dried over anhydrous Na2SO4 and evaporated to give CBFM as pale yellow oil with an isolated yield of 82%. 1H NMR (CDCl3, 400 MHz): delta/ppm: 3.96 (3H, s, OCH3), 7.41-7.46 (2H, m, Ar-H), 7.51-7.54 (1H, m, Ar-H), 7.75-7.78 (1H, m, Ar-H); 13C NMR (CDCl3, 100 MHz): delta/ppm: 53.9, 127.9, 131.2, 132.2, 133.9, 134.5, 135.0, 164.1, 186.9. |
With toluene-4-sulfonic acid; In toluene; for 2.0h;Reflux; | General procedure: A mixture of mandelic acid(12 mmol), alcohol (1.5 eq) , TsOH (500 mg) and toluene(20mL) wasrefluxed for 2 h. The resultant mixture was diluted with NaHCO3(sat.aq.)(3X10mL) and water( 2X10mL) and dried over Na2SO4.Flash chromatography on silica gel (eluent: ethyl acetate/petroleum ether =6:1) gave the correspondingracemic mandelate ester. | |
With sulfuric acid; at 80℃; for 3.0h; | Example 3. Preparing racemic 2-chloro-2-(2-chloro phenyl)acetic acid alkyl ester(ld, Ie, If); [52][53] 3g of <strong>[10421-85-9]2-chloromandelic acid</strong> was dissolved into 40 ml of methanol and after adding88 D of HSO , the mixture was heated and stirred at 80 0C for 3 hours. After removing solvent, water and ethyl acetate were added, then NaOH was added for neutralization. The product was extracted and distilled under reduced pressure. 2.1 ml of sulfonyl chloride was added to the previously produced substance and after 12 hours of stirring at 65 0C, solvent was removed. 2-chloro-2-(2-chloro phenyl)acetic acid methyl ester was prepared by adding water and ethyl acetate and washing 3 times. Furthermore, by using ethanol and butanol instead of methanol, 2-chloro-2-(2-chloro phenyl)acetic acid ethyl ester and 2-chloro-2-(2-chloro phenyl)acetic acid butyl ester were prepared respectively.[54] 2-chloro-2-(2-chloro phenyl)acetic acid methyl ester(ld):[55] 1H-NMRQOOMHz) delta(ppm) = 3.79(s, IH), 5.88(s, IH), 7.31(m,2H), 7.40(m,lH),7.63(m, IH)[56][57] 2-chloro-2-(2-chloro phenyl)acetic acid ethyl ester(le):[58] 1H-NMRQOOMHz) delta(ppm) = 1.26(t, 3H, J=14.1 Hz), 4.25(m, IH), 5.86(s, IH),7.32(m, 2H), 7.40(m, IH), 7.63(m, IH)[59][60] 2-chloro-2-(2-chloro phenyl)aceetic acid butyl ester(lf) :[61] 1H-NMRQOOMHz) delta(ppm) = O.88(t, 3H, J=14.4 Hz), 1.3 l(m, 2H), 1.61(m, 2H),4.19(t, 2H, J=13.5 Hz), 5.87(s, IH), 7.32(m, 2H), 7.40(m, IH), 7.63(m, IH) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; water; In 1,4-dioxane; for 6.0h;Reflux; | General procedure: A mixture of cyanohydrin (14 mmol), 37% HCl (5mL) and dioxane (10 mL) was refluxed for 6 h. The resultant mixture was dilutedwith water (10mL) and extracted with ethyl acetate (3X10mL).The pH value of the organic phase was adjusted to pH=2 with NaHCO3(sat.aq.). The aqueous phase was extracted with ethyl acetate (3X10mL).Thecombined organic phase was washed with brine (3×10 mL) and dried over Na2SO4. Flash chromatographyon silica gel (eluent: ethyl acetate/petroleum ether =2:1) gave the corresponding racemicmandelic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | General procedure: A mixture of 1.52g (10mmol) racemic mandelic acid MA, 0.27g (2.5mmol) of Na2CO3, and 0.80g (5.0mmol) of (R)-(-)-3-(aminomethyl)-5-methylhexanoic acid (R)-PREG was dissolved in 6.1mL of hot water. The crystalline diastereomeric salt appeared by gradually cooling down the solution to 26C and was then separated from the mother liquor by filtration after 15min. In order to decompose the diastereomer, a mixture of 1.9mL of 25% aqueous ammonia and 2.0mL of water was added to the crystals. Next, 0.70g (4.4mmol) of crystalline (R)-(-)-3-(aminomethyl)-5-methylhexanoic acid (R)-PREG was filtered off after 3h of crystallization time, after which 1.5mL of 37% hydrochloric acid was added to the mother liquor to afford 0.43g (56%) of (R)-(-)-mandelic acid (R)-MA with an eeD of 80% that was separated from the mother liquor after 2h of crystallization (Table 2, entry 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Substitution in the procedure of example 2 for the D-(-)-2-formyloxy-2-phenylacetyl chloride used therein of an equimolar quantity of monosubstituted D-(-)-2-formyloxy-2-phenylacetyl chloride prepared from the following monosubstituted D-mandelic acids: D-2-chloro-mandelic acid; D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ... | ||
Substitution in the procedure of example 2 for the D-(-)-2-formyloxy-2-phenylacetyl chloride used therein of an equimolar quantity of a D-mandelic acid carboxyanhydride prepared from the following D-mandelic acids by treating the mandelic acid with phosgene as described supra. D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ... | ||
Substitution for the D-mandelic acid carboxyanhydride in the procedure of Example 1 of an equimolar weight of the carboxyanhydrides prepared in similar fashion from the monosubstituted D-mandelic acids D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ... |
Substitution for the D-mandelic acid carboxyanhydride in the procedure of Example 10 of an equimolar weight of the carboxyanhydrides prepared in similar fashion from the monosubstituted D-mandelic acids D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ... | ||
Substitution of the D-mandelic acid carboxyanhydride in the procedure of Example 1 of an equimolar weight of the carboxyanhydrides prepared in similar fashion from the monosubstituted D-mandelic acids D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ... |
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