Structure of 127733-47-5
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CAS No. : | 127733-47-5 |
Formula : | C10H9F6N |
M.W : | 257.18 |
SMILES Code : | C[C@@H](N)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 |
MDL No. : | MFCD03093012 |
* 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 |
---|---|---|
In hexane; toluene; at 20 - 70℃; for 24.5h; | 1.02 g (3.97 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.68 g (3.59 mmol, 0.9 eq) of p-toluenesulfonic acid monohydrate were added to 6.5 ml of toluene, followed by stirring for 30 minutes at 60-70 C., the addition of 6 ml of n-hexane and allowing to cool to room temperature and stand for one day. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.20 g of crystals having the structure represented by the formula below and 1.44 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 82.7% ee (major form is the S form) and 74.2% ee (major form is the S form). [C00039] [00180] 1H-NMR (TMS, DMSO): 1.54 (d, 6.8 Hz, 3H), 2.28 (s, 3H), 4.69 (q, 6.8 Hz, 1H), 7.10 (d, 8.3 Hz, 2H), 7.46 (d, 8.3 Hz, 2H), 8.17 (s, 1H), 8.23 (s, 2H), 8.30 (br, 31). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; for 12.5h;Heating / reflux; | 0.94 g (3.64 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.55 g (3.64 mmol, 1 eq) of d-tartaric acid were added to 30 ml of methanol, followed by stirring for 30 minutes under reflux, allowing to cool to room temperature and stand for one half day. The precipitated crystals were filtered, washed with a small amount of methanol and vacuum dried to obtain 1.01 g of crystals having the structure represented by the formula below and 0.48 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 91.4% ee (major form is the S form) and 43.8% ee (major form is the S form). [C00040] [00182] 1H-NMR (TMS, DMSO): 1.45 (d, 6.8 Hz, 3H), 3.92 (s, 2H), 4.52 (q, 6.8 Hz, 1H), 6408 (s, 1H), 8.19 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hexane; toluene; for 48.5h;Heating / reflux; | 0.64 g (2.49 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=3.8:1) and 0.17 g (1.12 mmol, 0.45 eq) of (S)-mandelic acid were added to 3 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.5 ml of n-hexane and allowing to cool to room temperature and stand for 2 days in a refrigerator. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.53 g of crystals having the structure represented by the formula below and 0.28 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 96.1% ee (major form is the S form) and 4.7% ee (major form is the S form). [C00041] [00184] 1H-NMR (TMS, DMSO): 1.39 (d, 6.8 Hz, 3H), 4.41 (q, 6.5 Hz, 1H), 4.71 (d, 2.0 Hz, 1H), 7.19 (t, 7.3 Hz, 1H), 7.26 (t, 7.3 Hz, 2H), 7.36 (d, 7.3 Hz, 2H), 8.01 (s, 1H), 8.15 (s, 2H).Example 33Recrystallization Purification by (s)-Mandelic Acid Salt of Optically Active 1-(3.5-Bis-trifluoromethylphenyl)ethylamine (5a) [00185] 0.80 g (3.10 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=8.8:1) and 0.47 g (3.09 mmol, 1 eq) of (S)-mandelic acid were added to 4.5 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.8 ml of n-hexane, allowing to cool to room temperature, adding seed crystals and allowing to stand for 3 hours. The precipitated crystals were filtered, washed with a small amount of a-hexane and vacuum dried to obtain 0.89 g of crystals having the structure represented by the formula below and 0.35 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 90.7% ee (major form is the S form) and 58.1% ee (major form is the S form). [C00042] [00186] The 1H-NMR spectrum was the same as that of Example 32. | |
In toluene; at 20 - 80℃; for 1.5h;Heating; | 0.89 g of (S)-mandelic acid salt of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a) (5a (S)-mandelate, enantiomer ratio/S form:R form=95.5:4.5) were added to 10 ml of toluene, followed by stirring for 30 minutes at 80 C. and allowing to cool to room temperature and stand for 1 hour. The precipitated crystals were filtered, washed with a small amount of toluene and vacuum dried to obtain 0.71 g of crystals having the structure represented by the formula below and 0.18 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 99.7% ee (major form is the S form) and 82.7% ee (major form is the S form). [C00043] [00188] The 1H-NMR spectrum was the same as that of Example 32. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With hydrogen;5%-palladium/activated carbon; In ethanol; at 55℃; under 1500.15 Torr; for 12.0h; | [00108] 181 mg (0.5 mmol) of the crude product of optically active secondary amine (4a) produced in Example 7 and 18 mg (0.25 wt %) of 5% palladium/active carbon (water content: 50 wt %) were added to 2 ml of ethanol followed by setting the hydrogen pressure to 0.2 MPa and stirring for 12 hours at 55 C. Following completion of the reaction, the reaction liquid was filtered with Celite, concentrated and vacuum dried to obtain 96 mg of a crude product of the optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a) represented by the following formula: [C00016] [00109] The yield was 75%. Conversion, selectivity at the cleavage position (the previously mentioned a:b) and optical purity of the crude product were determined by chiral GC, and found to be 99%, a:b=1:99 and 76% ee, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; | 1.02 g (3.97 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.68 g (3.59 mmol, 0.9 eq) of p-toluenesulfonic acid monohydrate were added to 6.5 ml of toluene, followed by stirring for 30 minutes at 60-70 C., the addition of 6 ml of n-hexane and allowing to cool to room temperature and stand for one day. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.20 g of crystals having the structure represented by the formula below and 1.44 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 82.7% ee (major form is the S form) and 74.2% ee (major form is the S form). [C00039] [00180] 1H-NMR (TMS, DMSO): 1.54 (d, 6.8 Hz, 3H), 2.28 (s, 3H), 4.69 (q, 6.8 Hz, 1H), 7.10 (d, 8.3 Hz, 2H), 7.46 (d, 8.3 Hz, 2H), 8.17 (s, 1H), 8.23 (s, 2H), 8.30 (br, 31). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; | 0.94 g (3.64 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.55 g (3.64 mmol, 1 eq) of d-tartaric acid were added to 30 ml of methanol, followed by stirring for 30 minutes under reflux, allowing to cool to room temperature and stand for one half day. The precipitated crystals were filtered, washed with a small amount of methanol and vacuum dried to obtain 1.01 g of crystals having the structure represented by the formula below and 0.48 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 91.4% ee (major form is the S form) and 43.8% ee (major form is the S form). [C00040] [00182] 1H-NMR (TMS, DMSO): 1.45 (d, 6.8 Hz, 3H), 3.92 (s, 2H), 4.52 (q, 6.8 Hz, 1H), 6408 (s, 1H), 8.19 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; | 0.64 g (2.49 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=3.8:1) and 0.17 g (1.12 mmol, 0.45 eq) of (S)-mandelic acid were added to 3 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.5 ml of n-hexane and allowing to cool to room temperature and stand for 2 days in a refrigerator. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.53 g of crystals having the structure represented by the formula below and 0.28 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 96.1% ee (major form is the S form) and 4.7% ee (major form is the S form). [C00041] [00184] 1H-NMR (TMS, DMSO): 1.39 (d, 6.8 Hz, 3H), 4.41 (q, 6.5 Hz, 1H), 4.71 (d, 2.0 Hz, 1H), 7.19 (t, 7.3 Hz, 1H), 7.26 (t, 7.3 Hz, 2H), 7.36 (d, 7.3 Hz, 2H), 8.01 (s, 1H), 8.15 (s, 2H).Example 33Recrystallization Purification by (s)-Mandelic Acid Salt of Optically Active 1-(3.5-Bis-trifluoromethylphenyl)ethylamine (5a) [00185] 0.80 g (3.10 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=8.8:1) and 0.47 g (3.09 mmol, 1 eq) of (S)-mandelic acid were added to 4.5 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.8 ml of n-hexane, allowing to cool to room temperature, adding seed crystals and allowing to stand for 3 hours. The precipitated crystals were filtered, washed with a small amount of a-hexane and vacuum dried to obtain 0.89 g of crystals having the structure represented by the formula below and 0.35 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 90.7% ee (major form is the S form) and 58.1% ee (major form is the S form). [C00042] [00186] The 1H-NMR spectrum was the same as that of Example 32.Example 34Recrystallization Purification by (S)-Mandelic Acid Salt of Optically Active 1-(3,5-Bis-trifluoromethylphenyl)ethylamine (5a) [00187] 0.89 g of (S)-mandelic acid salt of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a) (5a (S)-mandelate, enantiomer ratio/S form:R form=95.5:4.5) were added to 10 ml of toluene, followed by stirring for 30 minutes at 80 C. and allowing to cool to room temperature and stand for 1 hour. The precipitated crystals were filtered, washed with a small amount of toluene and vacuum dried to obtain 0.71 g of crystals having the structure represented by the formula below and 0.18 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 99.7% ee (major form is the S form) and 82.7% ee (major form is the S form). [C00043] [00188] The 1H-NMR spectrum was the same as that of Example 32. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 101; (1alpha)-N-[(1alpha')-1-(3,5-Bis(trifluoromethyl)phenyl)ethyl]-1-(1-piperazinyl)indancarboxamide dihydrochloride; Step A; (1alpha')-1-[3,5-Bis(trifluoromethyl)phenyl]ethylamine; (1RS)-1-[3,5-Bis(trifluoromethyl)phenyl]ethylamine is converted into a salt using (L)-tartaric acid, the mixture of diastereoisomers thereby obtained is separated and then reconversion to the base is carried out on each of the two diastereoisomers. The expected product is the first of the enantiomers thereby obtained. |