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). |
[ 13011-88-6 ]

[ 10421-85-9 ]
[ 144-62-7 ]| 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, ... |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 22C36H54N2O2*10OV(2+)*10O4S(2-); In toluene; at 20℃; for 24.0h;Conversion of starting material; | A flask equipped with stirrer and internal thermometer is initially charged with 150 ml of toluene. 0.09 g (0.08×10-3 mol) of (R,R)-VO salen complex from Example 1 and 21.1 g (0.15 mol) of 2-chlorobenzaldehyde (freshly dist.) are added in succession with stirring. 10.1 g (0.375 mol) of hydrocyanic acid are then added all at once. The dark green, homogeneous solution is stirred at room temperature for 24 hours in the closed apparatus. The conversion according to GC is: 98%; 73% ee for the (S)-2-chloromandelic acid cyanohydrin. | |
| [VO(C6H10(NCHC6H2(C(CH3)3)2O)2)]; In toluene; at 20℃; for 24.0h;Conversion of starting material; | The cyanohydrin reactions were carried out as described in Example 2, using the complexes prepared in each of the Comparative Examples 1a-d. [0058] The results of the cyanohydrin reactions can be taken from the table | |
| 25C36H54N2O2*10OV(2+)*10O4S(2-); In toluene; at 20℃; for 24.0h;Conversion of starting material; | The cyanohydrin reactions were carried out as described in Example 2, using the complexes prepared in each of the Comparative Examples 1a-d. [0058] The results of the cyanohydrin reactions can be taken from the table |
| 29C36H54N2O2*10OV(2+)*10O4S(2-); In toluene; at 20℃; for 24.0h;Conversion of starting material; | The cyanohydrin reactions were carried out as described in Example 2, using the complexes prepared in each of the Comparative Examples 1a-d. [0058] The results of the cyanohydrin reactions can be taken from the table | |
| C360H540N20O95S15V15; In toluene; at 20℃; for 24.0h;Conversion of starting material; | The cyanohydrin reactions were carried out as described in Example 2, using the complexes prepared in each of the Comparative Examples 1a-d. [0058] The results of the cyanohydrin reactions can be taken from the table |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In dichlorobenzene, 1,2-; for 6.0h;Heating / reflux; Dean-Stark apparatus; | A mixture of 52.72 g of DL-<strong>[10421-85-9]2-chloromandelic acid</strong> and 40 g of 3-chloro-4-methylaniline in 400 ml of 1,2-dichlorobenzene is refluxed for 6 hours, while removing the water formed using Dean-Stark apparatus. After cooling to RT, the mixture is left to crystallize and the precipitate formed is filtered off by suction. The expected product is obtained after recrystallization from a DCM/iso ether mixture, m.p.=164 C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In dichlorobenzene, 1,2-; at 230℃; for 4.0h;Dean-Stark apparatus; | A mixture of 28 g of the compound obtained in the preceding step and 33.13 g of D,L-<strong>[10421-85-9]2-chloromandelic acid</strong> in 128 ml of 1,2-dichlorobenzene is heated at 230 C. for 4 hours, while removing the water formed using Dean-Stark apparatus. The reaction mixture is partially concentrated under vacuum and left to crystallize. The crystalline product formed is filtered off by suction and washed with iso ether. 40 g of the expected product are obtained |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; hydrazine; In dichloromethane; at 0℃; for 3.0h; | To a solution of <strong>[10421-85-9]2-chloromandelic acid</strong> (1.21 g, 6.49 mmol) and hydrazine hydrate (346 ; IL, 7.14 mmol) in CH2C12, EDC was added at 0 C. After stirring at this temperature for 3 h the product was collected by filtration and dried in vacuo to yield 880 mg (67%) of the title compound. MS (ESI) m/z 201 (M+1), 199 (M-1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| A N-p-Chlorophenyl-DL-2-chloromandelamide A mixture of 38.25 g of p-chloroaniline, 55.95 g of DL-<strong>[10421-85-9]2-chloromandelic acid</strong> and 280 ml of 1,2-dichlorobenzene is heated at 200 C. for 7 hours, the water formed being removed by means of a Dean-Stark apparatus. The reaction mixture is partially concentrated under vacuum and left to crystallize. The crystalline product formed is filtered off and washed with iso ether to give 44.92 g of the expected product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| A N-p-Methoxyphenyl-DL-2-chloromandelamide A mixture of 33.25 g of p-anisidine, 50 g of DL-<strong>[10421-85-9]2-chloromandelic acid</strong> and 250 ml of 1,2-dichlorobenzene is heated at 225 C. for 5 hours, the water formed being removed by means of a Dean-Stark apparatus. The reaction mixture is concentrated to about 150 ml and left to crystallize overnight. The crystals formed are filtered off and washed with ether to give 43.76 g of the expected product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| A N-p-Methylphenyl-DL-2-chloromandelamide A mixture of 32.1 g of p-toluidine, 55.95 g of DL-<strong>[10421-85-9]2-chloromandelic acid</strong> and 250 ml of 1,2-dichlorobenzene is refluxed for 6 hours, the water formed being removed by means of a Dean-Stark apparatus. The reaction mixture is cooled and the precipitate formed is filtered off and washed with iso ether to give 48 g of the expected product, which is used as such. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 45% | With phosphorus pentachloride; In methanol; | a Methyl 1-chloro-(2-chlorophenyl)acetate 93.3 g (0.5 mol) of pure <strong>[10421-85-9]2-chloromandelic acid</strong> are mixed with 208 g (1 mol) of phosphorus pentachloride and are heated progressively. The reaction begins at 60 C. and the temperature rises to 100 C. Heating is continued for 2 h between 120 and 130 C. When the evolution of hydrogen chloride gas has ceased, the mixture is returned to room temperature, is distilled on the water pump and is then taken up with 200 ml of methanol. The mixture is refluxed for 2 h. The reaction mixture is concentrated by means of a rotary evaporator and is taken up with methylene chloride and water. After phase separation and drying over anhydrous magnesium sulphate, the methylene chloride is stripped off by means of a rotary evaporator, and this yields 121 g of crude ester which is distilled between 80 and 90 C. at a pressure of 0.15 mm Hg (19.95 Pa). In this way 54.8 g of methyl 1-chloro(2-chlorophenyl)acetate are obtained, assayed at 90% by HPLC (high pressure liquid chromatography). Yield: 45%. |
[ 10421-85-9 ]
[ 106-47-8 ]
[ 104-94-9 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In 1,2-dichloro-benzene; | Preparation 3 (2-Chlorophenyl)-N-(4-chlorophenyl)hydroxyacetamide, Compound VII.1 A mixture of 60 g of <strong>[10421-85-9](2-chlorophenyl)hydroxyacetic acid</strong> and 41 g of 4-chlorophenylamine in 300 ml of 1,2-dichlorobenzene is heated to 200 C. The setup comprises a Dean and Stark apparatus and thus the water formed is removed during the reaction. Approximately 150 ml of solvent are distilled off and the expected compound is crystallized at 20 C. The solid obtained is rinsed with diisopropyl ether; M.p.=120 C. In the same way, (2-chlorophenyl)-N-(4-methoxyphenyl)hydroxyacetamide, compound VII.2, is prepared from 4-methoxyphenylamine; M.p.=130 C. In the same way, (2-chloro-4-fluorophenyl)-N-(4-chlorophenyl)hydroxyacetamide, compound VII.3, is prepared from (2-chloro-4-fluorophenyl)hydroxyacetic acid (synthesised according to J. Med. Chem., 1987, 30 (8), 1447, from 2-chloro-4-fluorobenzaldehyde and bromoform); M.p.=136 C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; | EDCI (0.0012 mol) was added to a mixture of 2-chloro-alpha-hydroxybenzene acetic acid (0.0011 mol), intermediate 11 (prepared according to A4.d) (0.0011 mol), HOBT (0.0001 mol) and N-ethyl-N-(l-methylethyl)-2-propanamine (0.213 ml) in DMF/THF (1/1 dried on molecular sieves) (10 ml) at room temperature. A second reaction mixture with 0.050 g of 2-chloro-alpha-hydroxybenzene acetic acid was set up (same conditions) and both mixtures were combined and evaporated to dryness. The residue was purified by HPLC method A. The recovered fraction was partially evaporated at 22C to remove the volatiles, followed by extraction with CH2Cl2. After drying (MgSO4), filtration and evaporation 380 mg yellow oily residue was obtained. This was suspended in boiling DIPE with few drops MeOH and stirred overnight at room temperature. After filtration and drying in vacuo at 500C a white powdery material was recuperated. Yield: 328 mg of compound 19 (RS). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In chloroform-d1; at 25℃; | General procedure: The chiral shift experiments were performed on a JEOL JNM-GSX 400 spectrometer at 25 C. Samples for analysis were prepared by mixing enantiomerically pure (R,R,R,R)-1 (0.0048 mmol) with several carboxylic acids (0.019 mmol) in CDCl3 (0.6 mL). For compounds 7b and 7d, CDCl3 containing acetone-d6 (10%) was used. |

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