Structure of 146137-78-2
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 146137-78-2 |
Formula : | C8H4F4O |
M.W : | 192.11 |
SMILES Code : | O=CC1=CC(C(F)(F)F)=CC=C1F |
MDL No. : | MFCD00061311 |
Boiling Point : | No data available |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.69 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.43 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.73 |
Solubility | 0.355 mg/ml ; 0.00185 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.37 |
Solubility | 0.821 mg/ml ; 0.00428 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.51 |
Solubility | 0.0588 mg/ml ; 0.000306 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 |
-5.79 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 |
2.0 |
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 |
1.0 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) |
1.47 |
* 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 potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; | Production Example 1; A mixture of 5.0 g of 2-fluoro-5- ( trifluoromethyl ) benzaldehyde, 3.3 g of methyl thioglycolate , 4.0 g of potassium carbonate and 50 ml of DMF was stirred at 60C for 2 hours, and then the reaction mixture was cooled . to room temperature. To the reaction mixture was added water, and extracted with tert-butyl methyl ether 3 times. The combined organic layer was washed with water, followed by saturated aqueous sodium chloride solution. The mixture was dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was recrystallized from methanol to obtain 6.3 g of methyl 5- ( trifluoromethyl ) benzo[ b] thiophene-2- carboxylate (the present compound 1) .[ The present compound 1]1 H-N R ( CDCI3 ) δ: 8.16(s, ' 1H) , 8.13(s, 1H) , 7.99(d, J=8.7Hz, 1H) , 7.67(d, J=8.7Hz, 1H) , 3.98(s, 3H) | |
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; | Production Example 1; A mixture of 5.0 g of 2-fluoro-5- ( trifluoromethyl ) benzaldehyde, 3.3 g of methyl thioglycolate, 4.0 g of potassium carbonate and 50 ml of DMF was stirred at 60C for 2 hours, and then the reaction mixture was cooled to room temperature. To the reaction mixture was added water, and extracted with tert-butyl methyl ether 3 times. The combined organic layer was washed with water, followed by saturated aqueous sodium chloride solution. The mixture was dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was recrystallized from methanol to obtain 6.3 g of methyl 5- (trifluoromethyl ) benzo[ b] thiophene-2- carboxylate. | |
6.3 g | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; | Production Example 1 A mixture of 5.0 g of 2-fluoro-5-(trifluoromethyl)benzaldehyde, 3.3 g of methyl thioglycolate, 4.0 g of potassium carbonate and 50 ml of DMF was stirred at 60 C. for 2 hours. The reaction mixture was cooled down to room temperature. To the reaction mixture was added water, and the mixture was extracted with tert-butyl methyl ether three times. The combined organic layers were washed with water and saturated saline, and dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was recrystallized from methanol, to obtain 6.3 g of methyl 5-(trifluoromethyl)benzo[b]thiophene-2-carboxylate (present condensed ring compound 1). [Present Condensed Ring Compound 1] [0100] 1H-NMR (CDCl3) δ: 8.16 (s, 1H), 8.13 (s, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 3.98 (s, 3H) |
6.3 g | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; | A mixture of 5.0 g of 2-fluoro-5-(trifluoromethyl)benzaldehyde, 3.3 g of methyl thioglycolate, 4.0 g of potassium carbonate and 50 ml of DMF was stirred at 60 C. for 2 hours. The reaction mixture was cooled down to room temperature. To the reaction mixture was added water, and the mixture was extracted with tert-butyl methyl ether three times. The combined organic layers were washed with water and saturated saline, and dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was recrystallized from methanol, to obtain 6.3 g of methyl 5-(trifluoromethyl)benzo[b]thiophene-2-carboxylate (present condensed ring compound 1). [Present Condensed Ring Compound 1]. 1H-NMR (CDCl3) δ: 8.16 (s, 1H), 8.13 (s, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 3.98 (s, 3H) |
General procedure: To a solution of 15a-m in DMF, K2CO3 (25 mmol, 3.45 g) wasadded and the mixturewas stirred at room temperature for 30 min.Then 16 was added dropwise. The reactionwas allowed to warm to60 C and monitored by TLC. The reaction was poured into waterand the mixture was extracted with ethyl acetate three times. Thecombined extracts were dried, concentrated and purified to affordthe intermediate 17a-m. Intermediate AM4a-mwas prepared in a similar manner as thatfor intermediate AM1, using 17a-m instead of 9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 120℃; for 10h; | To a solution of <strong>[146137-78-2]2-fluoro-5-trifluoromethylbenzaldehyde</strong> (10.0 mL, 68. 7 mmol) and 1-BOC-piperazine (15.4 g, 82.4 mmol) in 140 mL of DMF was added K2CO3 (47.4 g, 344 mmol). The reaction mixture was heated and stirred at 120 C for 10 hours. The reaction mixture was cooled to room temperature and diluted with 200 mL of EtOAc. The mixture was filtered, and the filter was washed well with EtOAc (3 x 50 mL). The filtrate was washed with 5% aqueous HCI (100 mL) and the aqueous layer was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with H20 (2 x 40 mL) and brine (50 mL). After drying (MgSO4), and concentration in vacuo, the residue was triturated with hexanes (3 x 20 mL) to give a brown oil. The brown oil slowly solidified to give the compound la as a yellow solid (22.3 g, 92%). |
92% | With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 120℃; for 10h; | EXAMPLE 3; 1- {4- 3- (2, 4-DICHLOROPHENYL) PROPIONYL]-1-PIPERAZINYL}-2- 1 S- (3- AMINOPROPIONYLAMIDO)-3-METHYLBUTYL]-4-TRIFLUOROMETHYLBENZENE 3-1; Step 3A. 2- [4''- (tert-Butoxvcarbonvl)-l-piperazinvl]-5-trifluoromethyl-benzaldehyde 3a :; To a solution of 2-fluoro-5-trifluoromethyl-benzaldehyde (10.0 mL, 68.7 mmol) and 1-BOC-piperazine (15.4 g, 82.4 mmol) in 140 mL of DMF was added K2CO3 (47.4 g, 344 mmol). The reaction mixture was heated and stirred at 120 C forlO hours. The reaction mixture was cooled to room temperature and diluted with 200 mL of EtOAc. The mixture was filtered, and the filter was washed well with EtOAc (3 x 50 mL). The filtrate was washed with 5% aqueous HC1 (100 mL) and the aqueous layer was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with H20 (2 x 40 mL), brine (50 mL), dried (MgS04), and concentrated in vacuo. The residue was triturated with hexanes (3 x 20 mL) to form a brown oil which slowly solidified to give 3a as a yellow solid (22.3 g, 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | EXAMPLE 60 5-Cyano-6-(2-fluoro-5-trifluoromethylphenyl)-4-methyl-2-oxo-3,6-dihydro-2H-pyrimidine-1-carboxylic acid ethyl ester Using <strong>[146137-78-2]2-fluoro-5-trifluoromethylbenzaldehyde</strong> and following the procedure of Example 25, intermediate XXIV was obtained in 41% yield and the title compound was obtained in 38% yield. 1H-NMR (CDCl3, 400 MHz): δ 8.27 (s, 1H), 7.65 (m, 1H), 7.58 (m, 1H), 7.25 (t, 1H, J=9.2 Hz), 6.03 (s, 1H), 4.28 (m, 2H), 2.20 (d, 3H, J=0.9 Hz), 1.29 (t, 3H, J=7.0 Hz). LC/MS (ES+) 372 (M+H)+, 394 (M+Na)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; | α-Ethenyl-2-fluoro-5-(trifluoromethyl)benzenemethanol 52.6 ml (0.0526 mol) of a 1M solution of vinylmagnesium bromide in THF are added dropwise at a temperature below 25 C. to a solution of 10.1 g (0.0526 mol) of 2-fluoro-5-(trifluoromethyl)benzaldehyde (prepared according to Example P) in 53 ml of anhydrous THF. The mixture is then stirred for 2 h 30 at room temperature. Hydrolysis is carried out with a saturated aqueous NH4 Cl solution while cooling between 10 and 20 C.; extraction is carried out with ether and the extract is washed with water, dried over Na2 SO4, filtered and evaporated under vacuum. The residue is used without subsequent purification in the following stage. Yd.: 11.6 g (quantitative) 1 H N.M.R. (CDCl3):2.3 (1H, broad s, exchangeable with D2 O), 4.7 to 6.5 (4H, m), 6.8 to 8.0 (3H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formic acid;aluminum nickel; In water; | 2-Fluoro-5-(trifluoromethyl)benzaldehyde A mixture of 18.7 g (0.0988 mol) of 2-fluoro-5-(trifluoromethyl)benzonitrile (prepared according to G. C. Finger et al., Chem. Comm., 1965, 430), 398 ml of 90% formic acid, 296 ml of water and 17.5 g of Raney nickel is heated for 5 hours at reflux and is then left standing overnight. The mixture is poured into 2.5 liters of water and extraction is carried out with methylene chloride (once 1 l and two times 500 ml). Filtration, washing with water, drying over Na2 SO4, filtration and distillation are carried out. Yd.: 10.1 g (53%) B.p.14 =70-72 C. IR: νc-o =1680 cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.0 M methylmagnesiumbromide (7.8 ml) was dropped, in a nitrogen atmosphere at 0 C, into the THF (30 ml) solution of 2-fluoro-5-trifluoromethyl benzaldehyde (3.0 g). After the mixture was warmed to room temperature, and was then stirred for 30 minutes, it was poured into a saturated ammonium chloride aqueous solution, and was then subjected to extraction with ethyl acetate. After its organic layer was washed with brine, and was then dried with anhydrous magnesium sulfate, it was filtered, and was then concentrated under reduced pressure to produce a crude chemical compound (58) (3.42 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In benzene;Heating / reflux; | The benzene (50 ml) solution of 2-fluoro-5-(trifluoromethyl)benzaldehyde (5.00 g), ethylene glycol (1.78 g), and p-toluene sulfonate monohydrate (0.49 g) were refluxed with heating over night. After the mixture was cooled to room temperature, it was poured into water, and was then subjected to extraction with ethyl acetate. After its organic layer was washed with brine, and was then dried with anhydrous magnesium sulfate, it was filtered, and its solvent was then evaporated to produce a crude chemical compound (39) (5.81 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NaBH(OAc)3; In dichloromethane; | (ii) (2S,3S)-3-(2-Fluoro-5-(trifluoromethyl)benzyl)amino-2-phenylpiperidine dihydrochloride (Compound 2) To a stirred suspension of Compound 1 (150 mg, 0.60 mmol) and 2-fluoro-5-(trifluoromethyl)benzaldehyde (116 mg, 0.60 mmol) in dry CH2Cl2 (6 ml) was added NaBH(OAc)3 (179 mg, 0.84 mmol) portionwise under nitrogen at room temperature. The reaction mixture was stirred at room temperature for 6.5 hr. This was basified with sat. NaHCO3 aq., extracted with CH2Cl2, dried with MgSO4, and concentrated to give crude (2S,3S)-3-(2-fluoro-5-(trifluoromethyl)benzyl)amino-2-phenylpiperidine as a colorless oil. This was purified with chromatography to give pure (2S,3S)-3-(2-fluoro-5-(trifluoromethyl)benzyl)amino-2-phenylpiperidine as a colorless oil (75 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium methylate; acetic acid; In water; | (i) 2-Methoxy-5-(trifluoromethyl)benzaldehyde (Compound 4) To a stirred and ice-cooled solution of NaOMe (904 mg, 4.68 mmol) was added 2-fluoro-5-(trifluoromethyl)benzaldehyde (500 mg, 2.60 mmol) portionwise. The dropping funnel employed was washed with THF. The resultant suspension was stirred at room temperature for 5 hr. The reaction mixture was neutralizing for acetic acid (0.3 ml, 5.0 mmol), the solvent was removed. To the solid residue was added water and the mixture was extracted with CH2Cl2. The combined CH2Cl2 extracts were washed with sat. NaHCO3 aq., dried with MgSO4, and concentrated to give crude Compound 4 as a white solid. This was purified with preparative TLC to give pure Compound 4 as a white crystalline (363 mg, 68.4%). 1H-NMR(CDCl3) 10.47(s, 1H), 8.11(d, J=2.2 Hz, 1H), 7.80(dd, J=8.8, 2.2 Hz, 1H), 7.10(d, J=8.8 Hz, 1H), 4.01(s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.77 g | With potassium carbonate; In acetonitrile; for 3.5h;Reflux; | 30 ml of acetonitrile suspension containing 2 g of the compound (H), 3.04 g of potassium carbonate, and 1.41 g of <strong>[146137-78-2]2-fluoro-5-trifluoromethylbenzaldehyde</strong> was refluxed for 3.5 hours. After being cooled to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saline and dried with anhydrous magnesium sulfate. 2.77 g of the target compound was obtained by evaporating the solvents under reduced pressure and purifying the residue with silica gel column chromatography (developing solution: mixed solvent of n-hexane and ethyl acetate). Melting temperature: 122-123C 1H-NMR(CDCl3, δppm):1.99-2.05(m, 2H), 2.12(s, 1H), 2.17(s, 1H), 2.21-2.28(m, 2H), 2.41(t, 1H), 2.45(t, 1H), 4.04(brs, 2H), 5.50(t, 1H), 6.79(d, 1H), 7.05(d, 1H), 7.61(d, 1H), 7.79(dd, 1H), 8.02(s, 1H), 8.44(s, 1H), 10.19(s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With potassium carbonate; at 60℃; for 5h; | Into a solution of 1 (3.00g, 15.6 mmol) in allyl alcohol was added K2CO3 (2.80g, 20.0 mmol). The mixture was heated to 60 C for 5 hours, cooled to room temperature, taken up in ethyl acetate, washed with water, then with brine and dried (Na2SO4), filtered and concentrated. The residue was purified on silica (eluted with a solution of ethyl acetate: hexane, 1 : 19) to give 2 (2.15g, 60% yield).1H NMR (300 MHz, CDCl3) δ 10.52 (s, IH), 8.12 (d, J= 1.5 Hz, IH), 7.76 (dd, J= 1.5, 8 Hz, IH), 7.07 (d, J= 8 Hz, IH), 6.18-5.84 (m, IH), 5.36-5.16 (m, 2H), 4.75 (d, J= 6 Hz, 2H). |
60% | With potassium carbonate; at 60℃; for 5h; | Into a solution of 2-fluoro-5-(trifluoromethyl)benzaldehyde (3.0Og, 15.6 mmol) in allyl alcohol was added K2CO3 (2.8Og, 20.0 mmol). The mixture was heated to 60 C for 5 hours, cooled to room temperature, taken up in ethyl acetate, washed with water, then with brine and dried (Na2SO^, filtered and concentrated. The residue was purified on silica (eluted with a solution of ethyl acetate: hexane, 1 :19) to give 40a (2.15g, 60% yield).1H NMR (300 MHz, CDCI3) 5 10.52 (S, 1H), 8.12 (d, J = 1.5 Hz, 1 H), 7.76 (dd,J = 1.5, 8 Hz, 1H), 7.07 (d, J = 8 Hz, 1H), 6.18-5.84 (m, 1H), 5.36-5.16 (m, 2H),4.75 (d, J = 6 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In toluene; at 120℃; | To toluene (5ml) are added 2-fluoro-5-trifluoromethyl-benzaldehyde (650mg) and dimethylamine hydrochloride (2.76g), followd by addition of potassium carbonate (1.4g), and the mixture is stirred at 120C overnight. The reaction solution is cooled to room temperature, and thereto are added ethyl acetate and water, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 49: 1→4: 1) to give 2-dimethylamino-5-trifluoromethyl-benzaldehyde (529mg). MS (m/z): 218 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In potassium carbonate; N,N-dimethyl-formamide; | Preparation 1 2-(3,4-Dichlorophenoxy)-5-Trifluoromethylbenzaldehyde Under N2 in a 50 mL round-bottomed flask fitted with a reflux condenser and magnetic stirrer were placed 0.829 g (6.0 mmol) of K2CO3 and 0.342 g (2.1 mmol) of 3,4-dichlorophenol (Aldrich Chem. Co., Milwaukee, Wis.) in 10 mL of anhydrous N,N-dimethylformamide (DMF). After stirring the mixture for 5 min., 0.384 g (2.0 mmol) of <strong>[146137-78-2]2-fluoro-5-trifluoromethylbenzaldehyde</strong> (Aldrich) was added and the mixture was heated to 90-95 C. overnight. After allowing the reaction to cool to room temperature, the mixture was diluted with water and EtOAc, the aqueous layer was extracted with additional EtOAc and the organic layers were combined, washed with H2O and saturated NaCl and dried over MgSO4. Removal of the solvent in vacuo gave a light amber colored oil, 0680 g. 1H-NMR (CDCl3, 400 MHz): d 10.46 (s, 1H), 8.18 (s, 1H), 7.74 (m, 1H), 7.48 (m, 1H), 7.23 (m, 1H), 6.97 (m, 2H). Mass spectrum (GCMS, m/z): 334 (m+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 90℃; | (3,5-Bis-trifluoromethyl-benzyl)-ethyl-amine (1.03g) is dissolved in N,N-dimethylformamide (10ml), and thereto are added 2-fTuoro-5- trifluoromethyl-benzaldehyde (1.45g) and potassium carbonate (1.48g), and the mixture is stirred under nitrogen atmosphere at 90C for 3 hours and at room temperature overnight. To reaction mixture is added a saturated brine and water, and the mixture is extracted five times with ethyl acetate and the organic layer is washed twice with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 10: 1) to give 2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl- amino]-5-trifluoromethyl-benzaldehyde (282mg). MS (m/z): 444 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In toluene; at 120℃; for 4h;Product distribution / selectivity; | 2-Fluoro-5-trifluoromethyl-benzaldehyde (l-3g) and cyclopropylmethyl-propyl-amine (1.15g) are dissolved in toluene (13ml), and thereto is added potassium carbonate (2.8Ig) and the mixture is stirred at 120C overnight. The reaction solution is cooled to room temperature, and thereto are added ethyl acetate and water, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = l:0→97:3) to give 2- (cyclopropylmethyl-propyl-amino) - 5-trifluoromethyl-benzaldehyde ( 1.7g) . MS (m/z): 286 [M+H]+. Example 76(1) 2-Fluoro-5-trifluoromethyl-benzaldehyde (5g) and cyclopropylmethyl- propyl-amine (5.57ml) is dissolved in toluene (50ml), and thereto is added potassium carbonate (10.7g) and the mixture is stirred at 120C overnight. The reaction solution is cooled to room temperature, and thereto are added ethyl acetate and water, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 20: 1) to give 2- (cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-benzaldehyde (6.8g). MS (m/z): 286 [M+H]+. Example 85 (1) 2-Fluoro-5-trifluoromethyl-benzaldehyde (5.38g) and cyclopropylmethyl-propyl-amine (4.75g) is dissolved in toluene (50ml), and thereto are added potassium carbonate (11.6g) and the mixture is stirred at 120C for 4 hours. The reaction solution is cooled to room temperature, and thereto is added water and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 19:1→4: 1) to give 2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-benzaldehyde (8.Og). MS (m/z): 286 [M+H]+. |
A318299 [89763-93-9]
2-Fluoro-4-(trifluoromethyl)benzaldehyde
Similarity: 0.98
A486704 [67515-60-0]
4-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.95
A166407 [188815-30-7]
3-fluoro-5-(trifluoromethyl)benzaldehyde
Similarity: 0.93
A127075 [112641-20-0]
2-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.91
A743548 [90176-80-0]
4-Fluoro-2-(trifluoromethyl)benzaldehyde
Similarity: 0.89
A318299 [89763-93-9]
2-Fluoro-4-(trifluoromethyl)benzaldehyde
Similarity: 0.98
A486704 [67515-60-0]
4-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.95
A166407 [188815-30-7]
3-fluoro-5-(trifluoromethyl)benzaldehyde
Similarity: 0.93
A127075 [112641-20-0]
2-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.91
A743548 [90176-80-0]
4-Fluoro-2-(trifluoromethyl)benzaldehyde
Similarity: 0.89
A318299 [89763-93-9]
2-Fluoro-4-(trifluoromethyl)benzaldehyde
Similarity: 0.98
A486704 [67515-60-0]
4-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.95
A166407 [188815-30-7]
3-fluoro-5-(trifluoromethyl)benzaldehyde
Similarity: 0.93
A127075 [112641-20-0]
2-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.91
A743548 [90176-80-0]
4-Fluoro-2-(trifluoromethyl)benzaldehyde
Similarity: 0.89
A318299 [89763-93-9]
2-Fluoro-4-(trifluoromethyl)benzaldehyde
Similarity: 0.98
A486704 [67515-60-0]
4-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.95
A166407 [188815-30-7]
3-fluoro-5-(trifluoromethyl)benzaldehyde
Similarity: 0.93
A127075 [112641-20-0]
2-Fluoro-3-(trifluoromethyl)benzaldehyde
Similarity: 0.91
A743548 [90176-80-0]
4-Fluoro-2-(trifluoromethyl)benzaldehyde
Similarity: 0.89