Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 1193-72-2 | MDL No. : | MFCD00018333 |
Formula : | C6H3BrCl2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ISHYFWKKWKXXPL-UHFFFAOYSA-N |
M.W : | 225.90 | Pubchem ID : | 70947 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 44.16 |
TPSA : | 0.0 Ų |
GI absorption : | Low |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.8 cm/s |
Log Po/w (iLOGP) : | 2.39 |
Log Po/w (XLOGP3) : | 4.05 |
Log Po/w (WLOGP) : | 3.76 |
Log Po/w (MLOGP) : | 4.22 |
Log Po/w (SILICOS-IT) : | 3.82 |
Consensus Log Po/w : | 3.65 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -4.29 |
Solubility : | 0.0117 mg/ml ; 0.0000518 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -3.75 |
Solubility : | 0.0398 mg/ml ; 0.000176 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.49 |
Solubility : | 0.00733 mg/ml ; 0.0000324 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.8 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
To a 2 L, 3-neck round bottom flask, equipped with a mechanic stirrer and an internal temperature controller, is added a solution of <strong>[1193-72-2]2,4-dichlorobromobenzene</strong> (65.5 g, 290.7 mmol) in 1.1 L [OF THF] under nitrogen. The solution is cooled to-95 C with a [MEOH/LIQUID] nitrogen bath. To this solution is added t-BuLi (400 mL, 1.6 M in pentane, 639.5 mmol) slowly via syringe pump followed by the addition of a solution of [OC-METHYL-Y-BUTYROLACTONE] (43.5 g, 434.8 mmol) in THF (100 mL). The internal temperature is controlled <-80 [C.] After 1 h stirring [<-80 C,] the reaction mixture is quenched with saturated NH4C1 solution and warmed to room temperature. Water (2 L) and EtOAc (1 L) are added and separated. The aqueous layer is extracted with EtOAc (2 x 2 L). The combined organic solutions is dried [(MGSO4)] and filtered. The filtrate is concentrated in vacuo to dryness to give 80.9 g of [1- (2,] 4-dichlorophenyl) -4- hydroxy-2-methylbutan-1-one as light yellow oil. The residue is used for Swern oxidation. To a 2 L, 3-neck round bottom flask, equipped with a mechanic stirrer and an internal temperature controller, is added DMSO (104.1 mL, 1465.7 mmol) and [CH2C12] (1.1 L). The solution is cooled to-80 C with a [MEOH/LIQUID] nitrogen bath. To this solution is added oxalyl chloride (63.9 mL, 732.9 mmol) slowly via syringe pump. The mixture is stirred at-80 C for 15 min followed by the addition of a solution of the above obtained crude [1- (2,] 4-dichlorophenyl) -4-hydroxy-2- methylbutan-1-one in [CH2C12] (150 mL) slowly via syringe pump. After stirring <-70 [C] for 1 h, to the mixture is added [ET3N] (456 mL, 3271.7 mmol). The cooling bath is removed after 5 min and the mixture is stirred at room temperature for 1.5 h. The mixture is diluted with hexanes (6 L) and washed with water (6 L). The aqueous layer is extracted with hexanes (6 L). The combined organic solutions is concentrated in vacuo to dryness and the residue is subjected to column chromatography (silica gel, 1/6 EtOAc/heptane) to give 36 g (50% for two steps) of light yellow oil as the title compound [:'H] NMR (400 MHz, CDCl3) 8 9.86 (s, 1H), 7.61 (d, J= 8.3 Hz, 1H), 7.49 (d, J=2. 0 Hz, 1H), 7.37 (dd, J=2. 0,8. 3 Hz, 1H), 3.81-3. 76 (m, 1H), 3.18 (dd, [J =] 8.2, 18.6 Hz, 1H), 2.65 (dd, [J =] 5.0, 18.6 Hz, 1H), 1.21 (d, [J =] 7.3 Hz, 3H) ; 13C NMR (100 MHz, [CDC13)] [# 206. ] 1,202. 4,139. 5,139. 2,134. 4,132. 7,132. 4,129. 6,48. 8, 42.0, 18.6 ; IR (liq. ) 2974,2936, 1996,1910, 1708,1585, 1457,1374, 1228, [1191,] 1106,1064, 978,828, [810 CM'' ;] MS (CI) [NZLZ] 247 (M+), 245 (M+). | ||
With tert.-butyl lithium; In tetrahydrofuran; pentane; at -80℃; for 1h; | To a 2 L, 3-neck round bottom flask, equipped with a mechanic stirrer and an internal temperature controller, is added a solution OF 2, 4-DICHLOROBROMOBENZENE (65.5 g, 290.7 MMOL) in 1.1 L of THF under nitrogen. The solution is cooled to-95 C with a MeOH/liquid nitrogen bath. To this solution is added t-BuLi (400 mL, 1.6 M in pentane, 639.5 MMOL) slowly via syringe pump followed by the addition of a solution of a-methyl-y-butyrolactone (43.5 g, 434.8 MMOL) in THF (100 mL). The internal temperature is controlled <-80 C. After 1 h stirring <-80 C, the reaction mixture is quenched with saturated NH4CI solution and warmed to room temperature. Water (2 L) and EtOAc (1 L) are added and separated. The aqueous layer is extracted with EtOAc (2 x 2 L). The combined organic solutions is dried (MGS04) and filtered. The filtrate is concentrated in vacuo to dryness to give 80.9 g of 1-(2, 4-dichlorophenyl)-4- HYDROXY-2-METHYLBUTAN-1-ONE as light yellow oil. The residue is used for Swern oxidation. To a 2 L, 3-neck round bottom flask, equipped with a mechanic stirrer and an internal temperature controller, is added DMSO (104.1 mL, 1465.7 MMOL) and CH2CI2 (1.1 L). The solution is cooled to-80 C with a MeOH/liquid nitrogen bath. To this solution is added oxalyl chloride (63.9 mL, 732.9 MMOL) slowly via syringe pump. The mixture is stirred at-80 C for 15 min followed by the addition of a solution of the above obtained crude 1- (2, 4-dichlorophenyl)-4- HYDROXY-2-METHYLBUTAN-1-ONE in CH2CI2 (150 mL) slowly via syringe pump. After stirring <-70 C for 1 h, to the mixture is added Et3N (456 mL, 3271.7 MMOL). The cooling bath is removed after 5 min and the mixture is stirred at room temperature for 1.5 h. The mixture is diluted with hexanes (6 L) and washed with water (6 L). The aqueous layer is extracted with hexanes (6 L). The combined organic solutions is concentrated in vacuo to dryness and the residue is subjected to column chromatography (silica gel, 1/6 EtOAc/heptane) to give 36 G (50% for two steps) of light yellow oil as the title compound : H NMR (400 MHz, CDCI3) E 9.86 (s, 1 H), 7.61 (d, J = 8.3 Hz, 1H), 7.49 (d, J = 2. 0 Hz, 1H), 7.37 (dd, J = 2. 0,8. 3 Hz, 1H) 3.81-3. 76 (m, 1H), 3. 18 (dd, J = 8.2, 18.6 Hz, 1H), 2.65 (dd, J = 5.0, 18.6 Hz, 1H), 1.21 (d, J = 7.3 Hz, 3H) ; 13C NMR (100 MHz, CDCI3) 8 206.1, 202.4, 139.5, 139.2, 134.4, 132.7, 132.4, 129.6, 48.8, 42.0, 18.6 ; IR (LIQ.) 2974,2936, 1996, 1910,1708, 1585, 1457, 1374,1228, 1191,1106, 1064,978, 828,810 cm-1 ; MS (CL) M/Z247 (M), 245 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; | Part C. tert-butyl (7bR,11aS)-6-(2,4-dichloroanilino)-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate. An oven dried three-necked round bottom flask was fitted with septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (134 mg, 0.36 mmol), <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (70 mg, 0.31 mmol), NaOtBu (60 mg, 0.62 mmol), and anhydrous toluene (5 mL). The solution was purged with argon at 80 C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (3.4 mg, 3.7 mumol), and BINAP (7 mg, 11.2 mumol) were added quickly. The resulting mixture was heated to 80 C. for 20 hours under argon while monitoring the consumption of starting material by TLC (50% ethyl acetate/hexanes). After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether and ethyl acetate. The resulting solution was concentrated and chromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient) yielding the title compound (78 mg, 48%) as a tan solid. 1H NMR(CDCl3, 300 MHz) delta 1.41 (s, 9H), 1.79-1.97 (m, 2H), 2.85-3.18 (m, 6H), 3.46-3.61 (m, 4H), 3.68 (s, 2H), 5.84 (s, 1H), 6.71 (d, 1H, J=1.9 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.89 (d, 1H, J=8.8 Hz), 7.01 (dd, 1H, J=2.3, 8.8 Hz), 7.29 (d, 1H, J=2.3 Hz) ppm. |
48% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; | Part C. tert-butyl (7bR,11aS)-6-(2,4-dichloroanilino)-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate. An oven dried three-necked round bottom flask was fitted with septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (134 mg, 0.36 mmol), <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (70 mg, 0.31 mmol), NaOtBu (60 mg, 0.62 mmol), and anhydrous toluene (5 mL). The solution was purged with argon at 80 C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (3.4 mg, 3.7 mumol), and BINAP (7 mg, 11.2 mumol) were added quickly. The resulting mixture was heated to 80 C. for 20 hours under argon while monitoring the consumption of starting material by TLC (50% ethyl acetate/hexanes). After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether and ethyl acetate. The resulting solution was concentrated and chromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient) yielding the title compound (78 mg, 48%) as a tan solid. 1H NMR (CDCl3, 300 MHz) delta 1.41 (s, 9H), 1.79-1.97 (m, 2H), 2.85-3.18 (m, 6H), 3.46-3.61 (m, 4H), 3.68 (s, 2H), 5.84 (s, 1H), 6.71 (d, 1H, J=1.9 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.89 (d, 1H, J=8.8 Hz), 7.01 (dd, 1H, J=2.3, 8.8 Hz), 7.29 (d, 1H, J=2.3 Hz) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluoroacetic acid; In toluene; | Part C. (7bR,11aS)-N-(2,4-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-amine, Bis Trifluoroacetic Acid Salt. A solution of tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indole-9(8H)-carboxylate (0.10 g, 0.29 mmol), <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (0.072 g, 0.318 mmol), BINAP (0.0011 g, 0.0017 mmol), sodium-t-butoxide, (0.072 g, 0.752 mmol) and Pd2DBA3 (0.0006 g, 0.00057 mmol) in 100 ml of degassed toluene was heated for 3 h at 90 C. The solution was cooled and filtered through a pad of silica gel and eluted with EtOAc. The volatiles were removed under reduced pressure and the product was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford a solid. LRMS (ES)+: 490.2 (M+H)+. This material was dissolved in 30 ml of CH2Cl2 followed by the addition of 10 ml of TFA and stirred at room temperature for 1 h, followed by removal of the volatiles under reduced pressure and the final product was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford the title compound of EXAMPLE 56. 1H NMR (300 MHz, DMSO-D6): delta 8.71-8.57 (broad m, 2H), 7.51 (m, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.95 (s, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.78 (s, 1H), 4.68 (d, J=14.2 Hz, 1H), 4.37 (d, J=14.2 Hz, 1H), 4.11 (d, J=12.8 Hz, 1H), 3.61 (t, J=11.7 Hz, 1H), 3.44-1.91 (broad m, 10H). LRMS (ES)+: 390.2 (M+H)+. | |
With trifluoroacetic acid; In toluene; | Part C. (7bR,11aS)-N-(2,4-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-amine, bis trifluoroacetic acid salt. A solution of tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indole-9(8H)-carboxylate (0.10 g, 0.29 mmol), <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (0.072 g, 0.318 mmol), BINAP (0.0011 g, 0.0017 mmol), sodium-t-butoxide, (0.072 g, 0.752 mmol) and Pd2DBA3 (0.0006 g, 0.00057 mmol) in 100 ml of degassed toluene was heated for 3 h at 90 C. The solution was cooled and filtered through a pad of silica gel and eluted with EtOAc. The volatiles were removed under reduced pressure and the product was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford a solid. LRMS (ES)+: 490.2 (M+H)+. This material was dissolved in 30 ml of CH2Cl2 followed by the addition of 10 ml of TFA and stirred at room temperature for 1 h, followed by removal of the volatiles under reduced pressure and the final product was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford the title compound of EXAMPLE 56. 1H NMR (300 MHz, DMSO-D6): delta 8.71-8.57 (broad m, 2H), 7.51 (m, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.95 (s, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.78 (s, 1H), 4.68 (d, J=14.2 Hz, 1H), 4.37 (d, J=14.2 Hz, 1H), 4.11 (d, J=12.8 Hz, 1H), 3.61 (t, J=11.7 Hz, 1H), 3.44-1.91 (broad m, 10H). LRMS (ES)+: 390.2 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride;tetrakis(triphenylphosphine)palladium (0); In methanol; ethanol; dichloromethane; water; toluene; | EXAMPLE 18 (3R,4S)-4-(2',4'-Dichlorobiphenyl-4-yloxy)-1-pyridin-3-yl-pentan-3-ol Prepared according to the method described in Example 12b) from (1S,2R)-4-[2-(tert-butyldimethylsilanyloxy)-1-methyl-4-pyridin-3-ylbutoxy]benzeneboronic acid (0.20 g, Example 11)), <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (0.218 g), 2M aqueous sodium carbonate (0.5 ml) and tetrakis(triphenylphosphine)palladium (0) (0.020 g)in toluene (5 ml) and ethanol (2 ml). The reaction mixture was heated at 100 C. under nitrogen for 4 hours. After cooling, the solution was concentrated under reduced pressure. Concentrated hydrochloric acid (1 ml) was added to a solution of the residue in methanol (5 ml) and the suspension was stirred at room temperature for 5 hours. The mixture was concentrated under reduced pressure and the residue partitioned between diethyl ether and water. The aqueous layer was neutralised with sodium hydrogen carbonate solution (in water) and the aqueous solution was extracted with ethyl acetate. The combined organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal-phase HPLC eluding with a gradient of 0-25% ethanol in dichloromethane to give a solid (0.064 g) from which the oxalate salt was prepared (0.054 g). m.p. 98-100 C. MS (APCI) 402.1, 404.1, 405.1 (M+H)+ 1H NMR (DMSO) 8.44(2H, m); 7.69(2H, bs); 7.49-7.32(5H, m); 7.00(2H, d); 4.34(1H, m); 3.38(1H, m); 2.83(1H, m); 2.70(1H, m); 1.86(1H, m); 1.66(1H, m); 1.25(3H, d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; dimethyl sulfoxide; benzene; | EXAMPLE 7 Preparation of Compound No. 11 (Reaction (a)) A mixture of <strong>[1193-72-2]2,4-dichloro-bromobenzene</strong> (22.6 g), N-[(+-)-2-(4-hydroxyphenoxy)propionyl]isoxazolidine (23.7 g) which was prepared as in Example 3, anhydrous potassium carbonate (14.5 g) and dimethylsulfoxide (200 ml) was stirred at 120 C. for 4 hours. After the reaction mixture was cooled, water and benzene were added thereto whereby to form two layers. The organic layer so separated was washed with 1 N aqueous sodium hydroxide solution and then with water and dried over anhydrous sodium sulfate. Removal of the solvent by a distillation in vacuo gave N-[(+-)-2-[4-(2,4-dichlorophenoxy)phenoxy]propionyl]isoxazolidine (30.9 g) as a pale yellow crystalline solid. Recrystallization from a mixture of n-hexane/ethyl acetate yielded a white crystalline solid. m.p. 115-118 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12.6 g (66%) | With n-butyllithium; In tetrahydrofuran; hexane; | EXAMPLE 4 Preparation of Chloromethyl(2,4-dichlorophenyl)dimethylsilane A solution of 17.0 g (0.075 mol) of <strong>[1193-72-2]2,4-dichlorobromobenzene</strong> and 10.8 ml (11.8 g, 0.082 mol) of chloro(chloromethyl)dimethylsilane in 100 ml of dry tetrahydrofuran was chilled to -70 under nitrogen and stirred while 49 ml (0.079 mol) of 1.6 molar n-butyllithium in hexane was added dropwise at a rate that held the mixture below -70. The resulting cloudy reaction mixture was allowed to warm to room temperature, poured into 400 ml of hexanes, filtered, and evaporated to leave 20.5 of yellow liquid. Distillation gave 12.6 g (66%) of the title compound as a colorless liquid: bp 83 (0.02 mm); nD24 1.5522; ir (neat) 1565, 1455, 1360, 1255, 1120, 1100, 1040, 825 cm-1; nmr (CDCl3) 0.5 (6H, s), 3.1 (2H, s), 7.0-7.5 (3H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.6 g (45%) | With n-butyllithium; In tetrahydrofuran; hexane; water; ethyl acetate; | EXAMPLE 8 Preparation of Chloromethyl(2,4-dichlorophenyl)methyl(phenyl)silane A solution of 13.6 g (0.060 mol) of <strong>[1193-72-2]2,4-dichlorobromobenzene</strong> and 12.3 g (0.060 mol) of chloro(chloromethyl)methyl(phenyl)silane (prepared as in Example 14) in 85 ml of dry tetrahydrofuran was chilled to -60 under nitrogen and stirred while 38 ml (0.060 mol) of 1.6 molar n-butyllithium in hexane was added dropwise at a rate that held the mixture below -55. The resulting red solution was allowed to warm to room temperature, treated with 5 ml of ethyl acetate to quench any unreacted organolithium reagent, and poured into 170 ml of water. The organic layer was separated, the aqueous phase was washed with 50 ml of hexanes, and the combined organic phases were washed three times with water and once with brine, dried over magnesium sulfate, and evaporated to leave 19.0 g of bright yellow oil. Distillation gave 8.6 g (45%) of the title compound as a colorless liquid: b.p. 125-130 (0.05 mm); nD21 1.5978; ir (neat) 3080, 3060, 2960, 2930, 1570, 1540, 1460, 1430, 1365, 1260, 1120, 1100, 1040, 820, 745, 735, 705 cm-1; nmr (CDCl3) 0.8 (3H, s), 3.4 (2H, s), 7.2-7.9 (8H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8% | With lithium hexamethyldisilazane; 2'-(di-tert-butylphosphanyl)-N,N-dimethyl-[1,1'-biphenyl]-2-amine;tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; at 20℃; for 72h; | General Procedure: To a 75 mL screw-cap round bottom flask equipped with a stir bar were added l-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong> (0.72 mL, 5.99 mmol), 3-methyl-piperazine-l-carboxylic acid tert-butyl ester (1.0 g, 4.99 mmol), 2-di-tert-butylphosphino-2'-(N,N- dimethylamine)biphenyl (51.1 mg, 0.15 mmol), tris(dibenzylideneacetone)dipalladium (45.7 rag, 0.05 mmol) and tetrahydrofuran (30 mL). The reaction flask was flushed with nitrogen for 5 minutes and then lithium bis(trimethylsilyl)amide (1 M in tetrahydrofuran, 6.99 mL, 6.99 mmol) was added in one portion. The reaction flask was sealed and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was concentrated in vacuo and the residue purified on silica gel using hexanes: acetone = 98:2 to give the desired product as an off-white solid (130 mg, 8 %). 1H NMR (300 MHz, CDCl3): delta 6.77 (t, IH)5 6.68 (d, 2H)5 4.10 (bs, IH), 3.85 (bss 2H), 3.12 (m, 4H). 1.48 (s, 9H), 1.04 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 100℃; for 2h; | To a solution of [l,4]diazepane-l-carboxylic acid tert-butyl ester (0.36g, 1.77mmol) in toluene (5mL) was added tris(dibenzylideneacetone)-dipalladium(0) (0.040 g, 0.044mmol), <n="61"/>R(+)-2,2'-bis(diphenylphosphino)-l,l ' -binapthyl (0.027 g, 0.044 mmol), sodium t-butoxide (0.13 g, 1.33 mmol), and l-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong> (0.20 g, 0.89 mmol). The solution was heated to 100 0C for 2 h. The reaction was cooled to room temperature, diethyl ether (5mL) was added and the resulting mixture filtered through a bed of diatomaceous earth. The residue was chromatographed on silica gel using hexane/ethyl acetate from 100% to 95% hexane in a gradient fashion, to give the title compound as a gum (0.13 g, 43%). The residue was used as is without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With sodium t-butanolate; 2-(di(tert-butyl)phosphinyl)biphenyl;palladium diacetate; In toluene; at 110℃; | General Procedure: To a 50 mL screw-cap round bottom flask equipped with a stir bar were added 1 -bromo-2,4-dichlorobenzene (2.0 g, 8.85 mmol), 2-methyl-piperazine-l -carboxylic acid tert-butyl ester (2.13 g, 10.6 mmol), palladium acetate (0.199 g, 0.89 mmol), 2-di-tert- butylphosphenylbiphenyl (0.264 g, 0.48mmol), sodium tert-butoxide (1.02 g, 10.6 mmol) and toluene (20 mL). The reaction flask was sealed and the reaction mixture was heated at 1 10 C overnight. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water (2 x 50 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified on silica gel using hexanes.diethyl ether = 95:5 to 90:10 in a gradient fashion, to give the desired product as yellow oil (858 mg, 28 %). 1H NMR (300 MHz, CDCl3): delta 7.28 (d, IH), 7.11 (dd, IH)5 6.85 (d, IH)5 4.28 (bs, IH), 3.89 (d, IH), 3.22 (m, IH), 3.08 (m, 2H), 2.67 (m, 2H), 1.43 (s, 9H), 1.34 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; chloroform; | Synthesis of 1-(2,4-Dichloro-phenyl)-piperazine BINAP (219 mg), Pd(II)acetate (397 mg, 0.176 mmol), tBuONa (1.19 g, 12.3 mmol), piperazine (837 mg, 9.73 mmol) and THF (40 mL) were mixed together and stirred at room temperature for 30 min under nitrogen atmosphere. <strong>[1193-72-2]2,4-dichlorobromobenzene</strong> (2 g, 8.84 mmol) in THF (10 mL) was added to the mixture drop wise and heated at 70 C. for 14 h. Excess THF was then evaporated and extracted with ethyl acetate. The crude product was obtained on concentration of the ethyl acetate layer after washing with brine and drying. Flash chromatography on silica gel eluding with 2% MeOH in CHCl3 gave 1-(2,4-Dichloro-phenyl)-piperazine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Intermediate LL; 6-chloro-N-[5-[4-(2,4-dichlorophenyl)piperidine-l-carbonyl]-2-methyl-phenyl]pyridine-3- carboxamide; Step 1: Preparation of tert-butyl 4-(2,4-dichlorophenyl)piperidine- 1 -carboxylate; The title compound was prepared using the method described in Journal of Organic Chemistry (2004), 69(15), 5120 - 5123, starting from tert-butyl 4-hydroxypiperidine-l- <n="162"/>carboxylate and l-bromo-2,4-dichloro-benzene, m/z 274.17 (M - t-Bu+H)+ (t-Bu cleaved in LC-MS), retention time 3.36 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
529 mg (2 mmol) Ethyl 5-(4-chlorophenyl)-4-methyl-pyrazole-3-carboxylate, 452 mg (2 mmol) 2,4- dichloro-1-bromobenzene, 384 mg (4 mmol) NaOt-Bu, 23.0 mg Bis(dibenzylideneacetone)palladium(0) (2 mol%) and 31.5 mg 2-(N,N-dimethylamino)-2'-(dicyclohexylphosphino)biphenyl (4 mol%) are heated in 12 ml degassed toluene, free of water for 15 h to 120 C until the starting aryl bromide has been completely comsumed as judged by GC analysis. The reaction mixture is then cooled to room temperature, diluted with ether and filtered through celite. Water is added to the filtrate and the phases are separated. The aqueous phase is acidified by addition of HCl until pH = 1.5. The resulting mixture is stirred, the precipitate formed is filtered off and dried under vacuum. | ||
529 mg (2 mmol) Ethyl 5-(4-chlorophenyl)-4-methyl-pyrazole-3-carboxylate, 452 mg (2 mmol) 2,4- dichloro-1-bromobenzene, 384 mg (4 mmol) NaOt-Bu, 23.0 mg Bis(dibenzylideneacetone)palladium(0) (2 mol%) and 30.4 mg 2-Dicyclohexylphosphino-2'-methoxy-l,l'-biphenyl (4 mol%) are heated in 12 ml degassed toluene, free of water for 15 h to 120 C until the starting aryl bromide has been completely comsumed as judged by GC analysis. The reaction mixture is then cooled to room temperature, diluted with ether and filtered through celite. Water is added to the filtrate and the phases are separated. The aqueous phase is acidified by addition of HCl until pH = 1.5. The resulting mixture is stirred, the precipitate formed is filtered off and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium t-butanolate;bis(dibenzylideneacetone)-palladium(0); DavePhos; In toluene; at 120℃; for 15h;Product distribution / selectivity; | Method 1: 637 mg (2 mmol) N-piperidino-5-(4-chlorophenyl)-4-methyl-pyrazole-3-carboxamide, 452 mg (2 mmol) 2,4-dichloro-l-bromobenzene, 384 mg (4 mmol) NaOt-Bu, 23.0 mgBis(dibenzylideneacetone)palladium(0) (2 mol%) and 31.5 mg 2-(N,N-dimethylamino)-2'- (dicyclohexylphosphino)biphenyl (4 mol%) are heated in 12 ml degassed toluene, free of water for 15 h to 120 C until the starting aryl bromide has been completely comsumed as judged by GC analysis. The reaction mixture is then cooled to room temperature, diluted with ether and filtered through celite.Water is added to the filtrate and the phases are separated. The solvent of the organic layer is evaporated and the resulting residue is purified by chromatography silica gel using toluene/ethyl acetate (90/10; v/v). | |
With sodium t-butanolate;bis(dibenzylideneacetone)-palladium(0); dicyclohexyl(2'-methoxy[1,1'-biphenyl]-2-yl)phosphine; In toluene; at 120℃; for 15h;Product distribution / selectivity; | 637 mg (2 mmol) N-piperidino-5-(4-chlorophenyl)-4-methyl-pyrazole-3-carboxamide, 452 mg (2 mmol) 2,4-dichloro-l-bromobenzene, 384 mg (4 mmol) NaOt-Bu, 23.0 mgBis(dibenzylideneacetone)palladium(0) (2 mol%) and 30.4 mg 2-Dicyclohexylphosphino-2'-methoxy- l,l'-biphenyl (4 mol%) are heated in 12 ml degassed toluene, free of water for 15 h to 120 C until the starting aryl bromide has been completely comsumed as judged by GC analysis. The reaction mixture is then cooled to room temperature, diluted with ether and filtered through celite. Water is added to the filtrate and the phases are separated. The solvent of the organic layer is evaporated and the resulting residue is purified by chromatography silica gel using toluene/ethyl acetate (90/10; v/v). Crystallization from isopropylether give desired pure compund 1. | |
With sodium t-butanolate;2,2'-bis(diphenylphosphino)biphenyl; bis(dibenzylideneacetone)-palladium(0); In toluene; at 80℃; for 15h;Product distribution / selectivity; | 637 mg (2 mmol) N-piperidino-5-(4-chlorophenyl)-4-methyl-pyrazole-3-carboxamide, 452 mg (2 mmol) 2,4-dichloro-l-bromobenzene, 384 mg (4 mmol) NaOt-Bu, 23.0 mgBis(dibenzylideneacetone)palladium(0) (2 mol%) and 24.9 mg 2,2'-bis(diphenylphosphino)-l,r- biphenyl (4 mol%) are heated in 15 ml degassed toluene, free of water for 15 h to 80 C until the starting aryl bromide has been completely comsumed as judged by GC analysis. The reaction mixture is then cooled to room temperature, diluted with ether and filtered through celite. Water is added to the filtrate and the phases are separated. The solvent of the organic layer is evaporated and the resulting residue is purified by chromatography silica gel using toluene/ethyl acetate (90/10; v/v). Crystallization from isopropylether give desired pure compund 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
At room temperature, dry diethyl malonate (1139.7 g, 7.12 mol) is initially charged in a 1.6 l apparatus with anchor stirrer, and sodium ethoxide (244.1 g, 3.59 mol) is added as a solid. Owing to the energy of reaction released, the internal temperature increases to about 60 C. After the reaction is ended, the ethanol formed is distilled off under reduced pressure (400 mbar) and simultaneous increase of the temperature from 60 to 80 C. Then, at 80 C., the pressure is gradually reduced to 10 mbar. At atmospheric pressure, the residue is cooled to 75 C., and CuBr (53.3 g, 0.37 mol) and <strong>[1193-72-2]2,4-dichlorobromobenzene</strong> (361.2 g, 1.60 mol) are added successively over a period of 20 minutes. After a further 12 hours at 75 C. and 2 hours at 90 C., the reaction mixture is cooled to 15 C. and, with stirring, added to a mixture, cooled to 10 C., of hydrochloric acid (36% strength, 260.9 g) and water (512.8 g). The reaction mixture obtained is filtered. Following separation of the phases of the filtrate, water (514.0 g) is added to the organic phase, and the pH is adjusted to 4 by addition of potassium carbonate (4.0 g, 50% strength solution in water). The phases are separated again, and the organic phase is then freed from volatile components under reduced pressure (0.5 mbar) and up to an internal temperature of 123 C. According to quantitative 1H-NMR spectroscopy, 83.7% of residue (501.5 g) consisted of diethyl 2,4-dichlorophenylmalonate. This corresponds to a diethyl 2,4-dichlorophenylmalonate yield of 86.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Reference Example 82 1-(2,4-dichlorophenyl)-6-methoxyindan-1-ol To a mixture of magnesium (3.89 g, 160 mmol) and THF (100 mL) was added dropwise a solution of <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (4.18 g, 18.5 mmol) in THF (50 mL), and the mixture was stirred at room temperature for 2 hr to give a Grignard reagent. Then, a solution of 6-methoxyindan-1-one (10.0 g, 61.7 mmol) in THF (50 mL) was added dropwise thereto under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was poured into a mixture of ice and ammonium chloride, and the mixture was extracted with diethyl ether. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (12.6 g, yield 66%) as an oil. 1H-NMR (CDCl3) delta: 2.29 - 2.42 (1H, m), 2.57 (1H, s), 2.88 (2H, q, J = 10.2 Hz), 3.01 - 3.20 (1H, m), 3.73 (3H, s), 6.55 (1H, d, J = 2.3 Hz), 6.87 (1H, dd, J = 8.3, 2.3 Hz), 7.17 - 7.25 (2H, m), 7.37 (1H, d, J = 2.3 Hz), 7.53 (1H, d, J = 8.7 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 5h;Reflux; | After the compound C-8 (3.08 g, 10.0 mmol) and <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (2.25 g, 10.0 mmol) were completely dissolved in tetrahydrofuran (50 mL), 2M potassium carbonate aqueous solution (30 mL) was added thereto, and tetrakistriphenylphosphino palladium (231 mg, 2 mol%) was put thereinto, agitated and refluxed for 5 hours. After the reaction was finished, the temperature was cooled to normal temperature, and the produced solid was filtered. The filtered solid was dissolved in chloroform, dried with anhydrous magnesium sulfate, concentrated under the reduced pressure, and recrystallized with chloroform and hexane to prepare the compound C-9 (2.45 g, 75%). MS: [M]+=326 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 16h;Inert atmosphere; | General procedure: A mixture of64(1.075g, 5.5mmol), 1-bromo-4-chlorobenzene (1.03g, 5.4mmol), Cs2CO3(2.28g, 7mmol) and BINAP (0.05 equiv) in toluene (60mL) was purged with N2, Pd(OAc)2(110mg, 0.22mmol) was added and the mixture was stirred under reflux for 16h, then cooled, diluted with EtOAc, filtered and evaporated. The residue was chromatographed on silica gel, with EtOAc/CH2Cl2(2:1) eluting24(0.62g. 37%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
625 mg | To a stirred solution of <strong>[1193-72-2]2,4-dichloro-1-bromobenzene</strong> (2.0 g, 8.853 mmol) in anhydrous THF (10 mL) was drop-wise added isopropylmagnessium chloride (2M inTHF, 6.6 mL, 13.320 mmol) at RT and the mixture was stirred 1 h. A solution of cyclobutanone (1.0 mL, 13.280 mmol) in THF (10 mL) was added to the reaction mixture and stirred at RT for 18 h. The mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (2 x 100 mL) and dried overanhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue obtained was purified by silica gel column chromatography to yield 625 mg of the title product as a semi-solid. ?H NMR (300 MHz, DMSO-d6) oe: 1.58-1.62 (m, 1H), 1.99-2.06 (m, 1H), 2.28-2.32 (m, 2H), 2.51-2.58 (m, 2H), 5.46 (s, 1H), 7.38-7.45 (m, 2H), 7.51 (s, 1H). | |
625 mg | To a stirred solution of 2,4-dichloro-l-bromobenzene (2.0 g, 8.853 mmol) in anhydrous THF (10 mL) was drop-wise added isopropylmagnesium chloride (2 in THF, 6.6 mL, 13.320 mmol) at the RT and the reaction mixture was stirred 1 h. A solution of cyclobutanone (1.0 mL, 13.280 mmol) in THF (10 mL) was added to the reaction mixture and stirred at the RT for 18 h. The reaction mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (2 x 100 mL), dried over anhydrous sodium sulfate and filtered. The solvent was distilled off under the reduced pressure and the residue obtained was purified by silica gel column chromatography to yield 625 mg of the titled product. 1H NMR (300 MHz, DMSO- d6) delta: 1.58-1.62 (m, 1H), 1.99-2.06 (m, 1H), 2.28-2.32 (m, 2H), 2.51-2.58 (m, 2H), 5.46 (s, 1H), 7.38-7.45 (m, 2H), 7.51 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.19 g | To a cooled solution of <strong>[1193-72-2]2,4-dichloro-1-bromobenzene</strong> (2.0 mL, 16.733 mmol) in anhydrous THF (20 mL) was slowly added isopropyl magnesium bromide (2M in in THF, 12.5 mL, 25.099 mmol) at RT and stirred for 1 h. A solution of 1,3- dichloroacetone (3.1 g, 25.099 mmol) in THF (20 mL) was drop-wise added to thereaction mixture and allowed to stir at RT for 18 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (50 mL) followed by brine (50 mL) and dried over anhydrous sodium sulfate. The solution was filtered, concentrated and the residue thus obtained was purified by silicagel column chromatography to yield 1.19 g of the title compound as a semi-solid. ?HNMR (300 MHz, DMSO-d6) oe 4.00 (d, J = 11.7 Hz, 2H), 4.31 (d, J = 11.7 Hz, 2H),6.36 (s, 1H), 7.44-7.49 (m, 1H), 7.58-7.60 (m, 1H), 7.80 (d, J = 8.7 Hz, 1H). | |
1.19 g | To a cooled solution of 2,4-dichloro-l-bromobenzene (2.0 mL, 16.7 mmol) in anhydrous THF (20 mL) was slowly added 2M isopropylmagnesium bromide in THF (12.5 mL, 25.1 mmol) at the RT and it was stirred for 1 h. A solution of 1,3-dichloroacetone (3.1 g, 25.1 mmol) in THF (20 mL) was drop-wise added to the reaction mixture and allowed to stir at RT for 18 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (50 mL x 2). The combined organic layers were washed with water (50 mL) followed by brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue thus obtained was purified by silica gel column chromatography to yield 1.19 g of the titled compound. 1H NMR (300 MHz, DMSO-ifc) delta 4.00 (d, J = 11.7 Hz, 2H), 4.31 (d, J = 11.7 Hz, 2H), 6.36 (s, 1H), 7.44-7.49 (m, 1H), 7.58- 7.60 (m, 1H), 7.80 (d, = 8.7 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
685 mg | To a stirred solution of <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (2.0 g, 8.853 mmol) in anhydrous diethyl ether (10 mL) was added n-butyl lithium (1.6 M in ether, 6.0 mL, 9.738 mmol) drop-wise at -78 C and the reaction mixture was stirred at the sametemperature for 1 h. A solution of tetrahydropyrane-4-one (0.9 mL, 9.73 8 mmol) in THF (10 mL) was added to the reaction mixture at -78 C. The cooling bath was removed and the reaction mixture was stirred at room temperature for 4 h. The mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washedwith water (2 x 100 mL), brine (100 mL) and dried over anhydrous sodium sulfate. The solvent was distilled out under reduced pressure and the residue obtained was purified by silica gel column chromatography to yield 685 mg of the title product as a semi-solid. ?H NMR (300 MHz, DMSO-d6) oe 1.43 (d, J = 9.6 Hz, 2H), 2.49-2.52 (m, 2H), 3.73-3.78 (m, 4H), 5.36 (s, 1H), 7.43-7.52 (m, 2H), 7.82 (d, J = 8.7 Hz, 1H); ES I-MS (mlz) 244 (M-H). | |
221 mg | To a stirred solution of l-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong> (500 mg, 2.21 mmol) in diethyl ether (10 mL) was added n-butyl lithium (1.6 M in THF, 1.6 mL) drop-wise at -78 C under the nitrogen atmosphere and the reaction mixture was stirred at the same temperature for 30 min. A solution of tetrahydro-4H-pyran-4-one (0.24 mL, 2.65 mmol) in diethyl ether (10 mL) was added to the reaction mixture at -78 C. The cooling bath was removed and the reaction mixture was stirred at the room temperature for 18 h. The reaction mixture was diluted with saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with water (2 x 100 mL), brine (100 mL), dried over anhydrous sodium sulfate and filtered. The solvent was distilled under the reduced pressure and the residue obtained was purified by silica gel column chromatography to yield 221 g of the titled product. 1H NMR (300 MHz, DMSO-d6) delta 1.42 (d, = 13.2 Hz, 2H), 2.48- 2.57 (m, 2H), 3.71-3.79 (m, 4H), 5.35 (s, 1H), 7.41-7.51 (m, 2H), 7.78 (d, = 8.7 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37 mg | To a stirred solution of <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (1.0 g, 4.426 mmol) in dry THF(10 mL) was drop-wise added isopropylmagnessium chloride (2M in THF, 3.3 mL) at-10 C and the mixture was stirred at the same temperature for 1 h. A solution ofcyclopentanone (0.58 mL, 6.640 mmol) in THF (10 mL) was added to the reactionmixture and stirred at RT for 18 h. The mixture was quenched with saturatedammonium chloride solution (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (2 x 100 mL) and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue obtained was purified by silica gel column chromatography to yield 37 mgof the title product as a semi-solid. ?H NMR (300 MHz, DMSO-d6) oe 1.78-2.10 (m,6H), 2.23 (br s, 2H), 5.07 (s, 1H), 7.40 (d, J = 8.7 Hz, 1H), 7.51 (s, 1H), 7.79 (d, J =8.1 Hz, 1H). | |
37 mg | To a stirred solution of l-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong> (1.0 g, 4.426 mmol) in dry THF (10 mL) was drop- wise added isopropylmagnessium chloride (2M in THF, 3.3 mL) at -10 C and the reaction mixture was stirred at the same temperature for 1 h. A solution of cyclopentanone (0.58 mL, 6.640 mmol) in THF (10 mL) was added to the reaction mixture and stirred at the RT for 18 h. The reaction mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (2 x 100 mL), dried over anhydrous sodium sulfate and filtered. The solvent was distilled off under the reduced pressure and the residue obtained was purified by silica gel column chromatography to yield 37 mg of the titled product. 1H NMR (300 MHz, DMSO-i delta 1.78-2.10 (m, 6H), 2.23 (br s, 2H), 5.07 (s, 1H), 7.40 (d, = 8.7 Hz, 1H), 7.51 (s, 1H), 7.79 (d, / = 8.1 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9% | Reference Example-12 A solution of <strong>[1193-72-2]1-<strong>[1193-72-2]bromo-2,4-dichlorobenzene</strong></strong> (9.0 g, 39.8 mmol) in THF was added dropwise to a suspension of magnesium (1.07 g, 43.8 mmol) in THF at 40 C. (oil bath temperature) in the presence of a catalytic amount of iodine in an argon gas atmosphere, whereby a Grignard reagent was prepared. The Grignard reagent was added dropwise to a solution of diethyl oxalate (6.99 g, 47.8 mmol) in THF at -50 C., and the temperature was slowly raised to room temperature, followed by stirring for 43 hours. After the reaction was completed, the reaction solution was added little by little to saturated ammonium chloride aqueous solution under ice-cooling, and the resultant product was extracted with ether (100 mL*2, 50 mL*1). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, whereby a brown oily crude product (10.8 g) was obtained. This was purified by silica gel column chromatography (hexane:ethyl acetate=10:1), whereby ethyl 2-(2,4-dichlorophenyl)-2-oxoacetate (850 mg, yield: 9%) was obtained as a yellow oily material. 1H-NMR (400 MHz, CDCl3): delta1.40 (t, J=7.1 Hz, 3H), 4.42 (q, J=7.1 Hz, 2H), 7.39 (dd, J=2.0 and 8.4 Hz, 1H), 7.48 (d, J=2.0 Hz, 2H), 7.73 (d, J=8.4 Hz, 1H). |
Tags: 1193-72-2 synthesis path| 1193-72-2 SDS| 1193-72-2 COA| 1193-72-2 purity| 1193-72-2 application| 1193-72-2 NMR| 1193-72-2 COA| 1193-72-2 structure
[ 29682-44-8 ]
1-Bromo-2,4,5-trichlorobenzene
Similarity: 0.92
[ 29682-44-8 ]
1-Bromo-2,4,5-trichlorobenzene
Similarity: 0.92
[ 29682-44-8 ]
1-Bromo-2,4,5-trichlorobenzene
Similarity: 0.92
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :