Structure of 60646-30-2
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CAS No. : | 60646-30-2 |
Formula : | C16H11F3O |
M.W : | 276.25 |
SMILES Code : | FC(F)(F)[C@@H](O)C1=C2C=CC=CC2=CC3=CC=CC=C13 |
MDL No. : | MFCD00062968 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With silica gel bound (S)-N-[1-phenyl-3-(chlorodimethylsilyl)-propyl]-3,5-dinitrobenzamide (CSP-2); In hexane; isopropyl alcohol;Resolution of racemate;Purification / work up; | Enantiomers of test racemates 1-18, Figure 3, were separated on analytical HPLC columns (250 mm x 4.6 mm) loaded with CSP-I and CSP-2. Results typically show good performance, i.e., higher enantioseparation of the column loaded with CSP-2 over CSP-I, and the selected results obtained on CSP-2 are shown in Tables 1 and 2.TABLE 1 Enantiomer separations for some test racemate on a column filled with CSP-2 (250 mm x 4.6 mm ID), with hexane : z-PrOH = 9:1 as the mobile phase and a flow of 1 ml/min, 254 nm.TR tRi/min tR2/min alpha RsTABLE 2 Enantiomer separations for some test racemate on the column filled with CSP-2 (250 mm x 4.6 mm ID), with hexane : /-PrOH = 7:3 as the mobile phase and a flow of 1 ml/min, 254 nm. | |
With silica gel bound (S)-N-[1-(naphth-1-yl)-3-(chlorodimethylsilyl)-propyl]-3,5-dinitrobenzamide (CSP-4); In hexane; isopropyl alcohol;Resolution of racemate;Purification / work up; | Enantiomers of test racemates 1-18, Figure 3, were separated on analytical HPLC columns (250 mm x 4.6 mm) filled with CSP-3 and CSP-4. Results show typically good performance, i.e., higher enantioseparation of the column loaded with CSP-4 over CSP-3 and the selected results obtained on CSP-4 are shown in Tables 3 and 4. Generally CSP-4, compared to other stationary phases mentioned herewith, separates more enantiomers, but in some individual cases CSP-2 is more efficient. Selected chromatograms are shown in Figures 4-7.TABLE 3 Enantiomer separations for some test racemate on the column filled with CSP-4 (250 mm x 4.6 mm ED), with hexane : z-PrOH = 9:1 as the mobile phase and a flow of 1 ml/min, 254 nm. TABLE 4 Enantiomer separations for some test racemate on the column filled with CSP-4 (250 mm x 4.6 mm BD), with hexane : /-PrOH = 7:3 as the mobile phase and a flow of 1 ml/min, 254 nm. | |
With CSP 9803/5601; In chloroform;Resolution of racemate;Product distribution / selectivity; | The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor alpha, are indicated. |
With CSP 9803/5301; In chloroform;Resolution of racemate;Product distribution / selectivity; | The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor alpha, are indicated. | |
With CSP 9803/5801; In chloroform;Resolution of racemate;Product distribution / selectivity; | The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor alpha, are indicated. | |
In hexane; chloroform; isopropyl alcohol; at 25℃;Resolution of racemate;Purification / work up; | The separating agents prepared in Examples 1 and 2 were used as fillers, and filled in stainless columns each having a length of 25 cm and an inner diameter of 2 mm by a slurry filling method to make columns for enantiomeric isomers. Using those columns, optical resolution of enantiomeric compounds shown in Table 3 was performed by liquid chromatography. Analytical conditions are the mobile phase: hexane (H)/chloroform (C)/2-propanol (1) = 90/10/1, a flow rate: 0.1 or 0.2 ml/min, temperature: 25C, and detection at 254 nm. The separation coefficient (alpha) in the table was determined by the following formula.Separation coefficient (alpha) = k2'/k1' : In the formula, k1' = ((t1-t0)/t0) and k2' = ( (t2-t0) /t0) . Those t1 and t2 denote elution times of respective enantiomeric isomers, and t0 denotes an elution time of tri-tert-butylbenzene. Table 1 shows the results when the mobile phase was hexane (H)/chloroform (C)/2-propanol (I) = 90/10/1.; Comparative Example 4 The optical resolution of various enantiomeric compounds was performed using the separating agents prepared in Comparative Examples 1 to 3 by the same method as that in Example 3. Table 1 shows the results. [Table 1] H/C/I=90/10/1 FillerEx. 1Ex. 2Com. Ex. 1Com. Ex. 2Com. Ex. 3Silica gelMA-SiM-SiA-SiMA-SiA-SiPolysaccharide derivative6-CMDMPC6-CMDMPC6-CMDMPC6-CVDMPC6-CVDMPCAddition amount of styrene (%)101010--Immobilization rate (%)9080997050Enantiomeric compound 11.861.581.681.631.44Enantiomeric compound 21.601.951.01.41.62Enantiomeric compound 31.231.361.21.251.28Enantiomeric compound 41.211.231.21.151.16Enantiomeric compound 51.371.311.361.31.28Enantiomeric compound 62.523.152.52.412.45Enantiomeric compound 71.01.01.01.01.0Enantiomeric compound 81.201.271.121.211.26Enantiomeric compound 92.042.241.81.911.56Mean of alpha values1.561.681.431.471.45 | |
In hexane; isopropyl alcohol;Resolution of racemate;Purification / work up; | The optical resolution of the enantiomeric compounds shown in Table 3 was performed by the same method as that in Example 5, except that the separating agents prepared in Examples 1 to 4 were used as fillers, the mobile phase was changed to hexane (H)/2-propanol = 90/10, and the flow rate was changed to 0.1 ml/min. Table 2 shows the results. | |
With SiO2-supported cellulose tris(4-methylbenzoyl)carbamate; In hexane; isopropyl alcohol; at 25℃;Resolution of racemate;Product distribution / selectivity; | In a nitrogen atmosphere, 20 ml of pyridine or dimethylsulfoxide was added to 1 g of a polysaccharide (cellulose or amylose), and each of the corresponding isocyanates (1) to (3) and (6) was added thereto in an amount of 1.5 equivalents to that of hydroxyl groups of the polysaccharide, and stirred under heating to thereby obtain each of polysaccharide benzoyl carbamate derivatives (7) to (13) shown in Table 1. In a nitrogen atmosphere, 20 ml of pyridine or dimethylsulfoxide was added to 1 g of a polysaccharide (cellulose or amylose), and each of the corresponding isocyanates (1) to (3) and (6) was added thereto in an amount of 1.5 equivalents to that of hydroxyl groups of the polysaccharide, and stirred under heating to thereby obtain each of polysaccharide benzoyl carbamate derivatives (7) to (13) shown in Table 1. (b) Surface Treatment of Silica GelPorous silica gel (particle size of 7 mum) was reacted with 3-aminopropyl triethoxysilane for aminopropylsilane (APS) treatment.(c) Preparation of Filler for Liquid Chromatography0.225 g of each of the polysaccharide benzoyl carbamate derivatives (7) to (13) obtained in the above section (a) was dissolved in tetrahydrofuran (THF) or dimethylsulfoxide (DMSO), and 0.9 g of silica gel obtained in the above section (b) was evenly coated with the resulting solution. Then, the solvent was distilled off under reduced pressure, to thereby obtain a filler for enantiomeric isomers having the target polysaccharide derivative carried on silica gel.(d) Preparation of Column for Liquid ChromatographyThe filler obtained in the above section (c) was pressed and filled into a stainless column of 0.2 cmPhi×25 cmL through a slurry filling method, to thereby prepare an enantiomeric isomer separation column. The enantiomeric isomer separation columns prepared in Examples were each evaluated for asymmetry identifying power (retention factor k' value and separation factor alpha value) by using the following ten compounds by means of liquid chromatography. Table 2 shows the results.(Analysis Conditions) Mobile phase: hexane/2-propanol=90/10 (v/v)Flow rate: 0.1 ml/minDetection: 254 nmTemperature: 25 C. | |
With cellulose 3,5-dimethylphenylcarbamate; In hexane; isopropyl alcohol; at 20℃;Resolution of racemate;Product distribution / selectivity; | The optical resolution of ten kinds of racemic bodies (FIG. 3) with the column-1 obtained by the above-mentioned operation (column temperature: about 20 C.) was performed. A HPLC pump (trade name: PU-980) manufactured by JASCO Corporation was used. The detection and identification of a peak were performed with a UV detector (wavelength: 254 nm, trade name: UV-970, manufactured by JASCO Corporation) and an optical rotation detector (trade name: OR-990, manufactured by JASCO Corporation) under the following conditions: a mixture of hexane and 2-propanol at a ratio of 95:5 was used as an eluent, and its flow rate was 0.2 ml/min. It should be noted that the number of theoretical plates N was determined from the peak of benzene, and a time to for which the eluent passed through the column was determined from the elution time of 1,3,5-tri-tert-butylbenzene.It should be noted that conditions concerning, for example, HPLC and a detector used in the evaluation for optical resolution identical to those described above were used in the following examples and comparative examples.Table 1 shows the results of the optical resolution with the column-1. Values in the table are a capacity ratio k1' and a separation factor alpha, and a sign in parentheses represents the optical activity of an enantiomer which was previously eluted.It should be noted that the capacity ratio k1' and the separation factor alpha are defined by the following formulae. A capacity ratio and a separation factor were calculated in the following examples and comparative examples by using the same formulae.Capacity ratio k1'k1'=[(retention time of enantiomer)-(t0)]/t0 [Num 1] Separation factor alphaalpha=(capacity ratio of enantiomer to be retained more strongly)/(capacity ratio of enantiomer to be retained more weakly) [Num 2]; [Table 1] TABLE 1 Optical resolutions of columns 1 to 4 Column-1a Column-2b Column-3a Column-4b Racemates k1' alpha k1' alpha k1' alpha k1' alpha 1 7.61(-) 1.30 5.97(-) 1.23 6.02(-) 1.23 4.30(-) 1.21 2 5.42(+) 1.58 5.13(+) 1.37 6.02(+) 1.09 3.69(+) 1.26 3 4.01(-) 1.17 3.49(-) 1.76 3.34(-) 1.99 2.63(-) 1.74 4 11.49(+) 1.20 - 9.48(+) 1.19 5.63(+) 1.19 5 16.40(-) 3.90 7.96(-) 3.22 13.08(-) 2.80 5.38(-) 2.89 6 21.19(+) 1.26 13.59(+) 1.37 16.15(+) 1.43 9.08(+) 1.38 7 9.26(-) 1.13 7.44(-) 1.26 7.83(-) 1.29 5.57(-) 1.23 8 5.10(+) 1.26 2.35(+) 1.27 4.01(+) 1.27 - 9 20.00(-) 2.20 10.84(-) 2.50 24.13(-) 3.16 7.69(-) 2.57 10 20.75 1.00 6.63(+) 1.52 10.01(+) 1.91 4.12(+) 1.83 aEluent: hexane/2-propanol (95/5)bEluent: hexane/2-propanol (90/10) Column: 25 × 0.20 cm (i.d.), Flow rate: 0.2 ml/min | |
With cellulose 3,5-dimethylphenylcarbamate; In hexane; isopropyl alcohol;Resolution of racemate;Product distribution / selectivity; | The optical resolution of ten kinds of racemic bodies (FIG. 3) with the column-3 obtained by the above-mentioned operation were performed. The detection and identification of a peak were performed with a UV detector and an optical rotation detector under the following conditions: a mixture of hexane and 2-propanol at a ratio of 95:5 was used as an eluent, and its flow rate was 0.2 ml/min. It should be noted that the number of theoretical plates N was determined from the peak of benzene, and a time to for which the eluent passed through the column was determined from the elution time of 1,3,5-tri-tert-butylbenzene.Table 1 shows the results of the optical resolution with the column-3; [Table 1] TABLE 1 Optical resolutions of columns 1 to 4 Column-1a Column-2b Column-3a Column-4b Racemates k1' alpha k1' alpha k1' alpha k1' alpha 1 7.61(-) 1.30 5.97(-) 1.23 6.02(-) 1.23 4.30(-) 1.21 2 5.42(+) 1.58 5.13(+) 1.37 6.02(+) 1.09 3.69(+) 1.26 3 4.01(-) 1.17 3.49(-) 1.76 3.34(-) 1.99 2.63(-) 1.74 4 11.49(+) 1.20 - 9.48(+) 1.19 5.63(+) 1.19 5 16.40(-) 3.90 7.96(-) 3.22 13.08(-) 2.80 5.38(-) 2.89 6 21.19(+) 1.26 13.59(+) 1.37 16.15(+) 1.43 9.08(+) 1.38 7 9.26(-) 1.13 7.44(-) 1.26 7.83(-) 1.29 5.57(-) 1.23 8 5.10(+) 1.26 2.35(+) 1.27 4.01(+) 1.27 - 9 20.00(-) 2.20 10.84(-) 2.50 24.13(-) 3.16 7.69(-) 2.57 10 20.75 1.00 6.63(+) 1.52 10.01(+) 1.91 4.12(+) 1.83 aEluent: hexane/2-propanol (95/5)bEluent: hexane/2-propanol (90/10) Column: 25 × 0.20 cm (i.d.), Flow rate: 0.2 ml/min | |
With cellulose 3,5-dimethylphenylcarbamate; In hexane; isopropyl alcohol;Resolution of racemate;Product distribution / selectivity; | The optical resolution of nine kinds of racemic bodies (FIG. 3) with the column-2 obtained by the above-mentioned operation was performed. The detection and identification of a peak were performed with a UV detector and an optical rotation detector under the following conditions: a mixture of hexane and 2-propanol at a ratio of 90:10 was used as an eluent, and its flow rate was 0.2 ml/min. It should be noted that the number of theoretical plates N was determined from the peak of benzene, and a time to for which the eluent passed through the column was determined from the elution time of 1,3,5-tri-tert-butylbenzene.Table 1 shows the results of the optical resolution with the column-2. Values in the table are a capacity ratio k1' and a separation factor alpha, and a sign in parentheses represents the optical activity of an enantiomer which was previously eluted; [Table 1] TABLE 1 Optical resolutions of columns 1 to 4 Column-1a Column-2b Column-3a Column-4b Racemates k1' alpha k1' alpha k1' alpha k1' alpha 1 7.61(-) 1.30 5.97(-) 1.23 6.02(-) 1.23 4.30(-) 1.21 2 5.42(+) 1.58 5.13(+) 1.37 6.02(+) 1.09 3.69(+) 1.26 3 4.01(-) 1.17 3.49(-) 1.76 3.34(-) 1.99 2.63(-) 1.74 4 11.49(+) 1.20 - 9.48(+) 1.19 5.63(+) 1.19 5 16.40(-) 3.90 7.96(-) 3.22 13.08(-) 2.80 5.38(-) 2.89 6 21.19(+) 1.26 13.59(+) 1.37 16.15(+) 1.43 9.08(+) 1.38 7 9.26(-) 1.13 7.44(-) 1.26 7.83(-) 1.29 5.57(-) 1.23 8 5.10(+) 1.26 2.35(+) 1.27 4.01(+) 1.27 - 9 20.00(-) 2.20 10.84(-) 2.50 24.13(-) 3.16 7.69(-) 2.57 10 20.75 1.00 6.63(+) 1.52 10.01(+) 1.91 4.12(+) 1.83 aEluent: hexane/2-propanol (95/5)bEluent: hexane/2-propanol (90/10) Column: 25 × 0.20 cm (i.d.), Flow rate: 0.2 ml/min | |
With cellulose 3,5-dimethylphenylcarbamate; In hexane; isopropyl alcohol;Resolution of racemate;Product distribution / selectivity; | The optical resolution of nine kinds of racemic bodies (FIG. 3) with the column-4 obtained by the above-mentioned operation was performed. The detection and identification of a peak were performed with a UV detector and an optical rotation detector under the following conditions: a mixture of hexane and 2-propanol at a ratio of 90:10 was used as an eluent, and its flow rate was 0.1 ml/min. It should be noted that the number of theoretical plates N was determined from the peak of benzene, and a time to for which the eluent passed through the column was determined from the elution time of 1,3,5-tri-tert-butylbenzene. Table 1 shows the results of the optical resolution with the column-4.[Table 1] TABLE 1 Optical resolutions of columns 1 to 4 Column-1a Column-2b Column-3a Column-4b Racemates k1' alpha k1' alpha k1' alpha k1' alpha 1 7.61(-) 1.30 5.97(-) 1.23 6.02(-) 1.23 4.30(-) 1.21 2 5.42(+) 1.58 5.13(+) 1.37 6.02(+) 1.09 3.69(+) 1.26 3 4.01(-) 1.17 3.49(-) 1.76 3.34(-) 1.99 2.63(-) 1.74 4 11.49(+) 1.20 - 9.48(+) 1.19 5.63(+) 1.19 5 16.40(-) 3.90 7.96(-) 3.22 13.08(-) 2.80 5.38(-) 2.89 6 21.19(+) 1.26 13.59(+) 1.37 16.15(+) 1.43 9.08(+) 1.38 7 9.26(-) 1.13 7.44(-) 1.26 7.83(-) 1.29 5.57(-) 1.23 8 5.10(+) 1.26 2.35(+) 1.27 4.01(+) 1.27 - 9 20.00(-) 2.20 10.84(-) 2.50 24.13(-) 3.16 7.69(-) 2.57 10 20.75 1.00 6.63(+) 1.52 10.01(+) 1.91 4.12(+) 1.83 aEluent: hexane/2-propanol (95/5)bEluent: hexane/2-propanol (90/10) Column: 25 × 0.20 cm (i.d.), Flow rate: 0.2 ml/min | |
With cellulose (3,5-dimethylphenyl)carbamate chiral stationary phase 1; In hexane; isopropyl alcohol; at 20℃;Resolution of racemate; | The sample solution was prepared by dissolving the racemates in a hexane/IPA (90/10, v/v) mixture. The column was 25 cm long with an internal diameter of 0.46 cm, hexane/IPA or hexane/IPA/THF or hexane/IPA/chloroform were used as the mobile phase, the flow rate was 1.0 or 0.5mL/min at 20 C and the detection wavelength was set to 214 or 254 nm for the test solutes. The mobile phases were filtered and sonicated prior to use. The void time of the columns was determined by 1,3,5-tri-tert-butylbenzene. |