Structure of 269410-10-8
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CAS No. : | 269410-10-8 |
Formula : | C15H21BO5 |
M.W : | 292.14 |
SMILES Code : | COC(=O)C1=CC(B2OC(C)(C)C(C)(C)O2)=C(OC)C=C1 |
MDL No. : | MFCD06797995 |
InChI Key : | BFNCIPMAUSEQIE-UHFFFAOYSA-N |
Pubchem ID : | 21923902 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00381] In a reaction tube under nitrogen, a mixture of PdCl2(dppf)CH2Cl2 (21 mg; 0.026 mmol) and triethylamine (0.34 ml; 2.44 mmol) in dioxane (2.5 ml; dried over 4 A sieves) was sealed and stirred at 80 C. overnight (18 h). After cooling to room temperature, HB(pin) (0.19 ml; 1.31 mmol) was added followed by methyl 3-iodo-4-methoxybenzoate (251 mg; 0.859 mmol) in dioxane (2.5 ml; dried over 4 A sieves) the reaction mixture was stirred at 80 C. GC analysis after 18 hours showed the desired borate compound at 13.0 minutes. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; for 24h;Inert atmosphere; Reflux; | Under argon atmosphere, a solution of 16 (71.2 mg, 0.291 mmol) and 10 (70.8 mg, 0.268 mmol) in dioxane (2 mL) was added to [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (22.1 mg, 0.027 mmol), and tripotassium phosphate (175 mg, 0.824 mmol) at room temperature. After being refluxed for 24 h, the reaction mixture was evaporated. The residue was chromatographed over silica gel eluted by hexane-EtOAc (9:1) to give 17 (75.4 mg, 0.249 mmol, 93%). Data for 17: colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.98-8.02 (2H, m), 7.46 (2H, d, J=8.9 Hz), 7.09 (2H, d, J=8.9 Hz), 6.97 (1H, d, J=9.1 Hz), 5.21 (2H, s), 3.89 (3H, s), 3.86 (3H, s), 3.50 (3H, s); 13C NMR (100 MHz, CDCl3) δ 166.8, 160.1, 156.6, 132.2, 131.0, 130.6 (2C), 130.4, 130.0, 122.6, 115.8 (2C), 110.5, 94.4, 55.9, 55.7, 51.8; LREIMS m/z 302 [M]+ (100%), 272 (36%), 226 (11%); HREIMS m/z 302.1141 [M]+ (302.1154 calcd for C17H18O5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; for 18h;Reflux; Inert atmosphere; | Under argon atmosphere, a solution of methyl 3-bromo-4-methoxybenzoate (15)14 (200 mg, 0.816 mmol) in dioxane (5 mL) was added to bis(pinacolato)diboron (228 mg, 0.898 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (66.7 mg, 0.082 mmol), and potassium acetate (240 mg, 2.448 mmol) at room temperature. After being refluxed for 18 h, the reaction mixture was evaporated. The residue was chromatographed over silica gel eluted by hexane/ EtOAc (9:1) to give 16 (153 mg, 0.523 mmol, 64%). Data for 16: colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.34 (1H, d, J=2.4 Hz), 8.09 (1H, dd, J=8.7, 2.4 Hz), 6.87 (1H, d, J=8.7 Hz), 3.88 (6H, s), 1.36 (12H, s); 13C NMR (100 MHz, CDCl3) δ 167.6, 166.8, 138.5, 134.5, 122.1, 109.8, 83.7 (2C), 55.9, 51.7, 24.8 (4C) (because a boron atom was bonded to C-3, the C-3 signal was highly broadened and not observed); LREIMS m/z 292 [M]+ (100%), 277 (19%), 261 (14%), 249 (31%), 235 (19%), 192 (37%); HREIMS m/z 292.1469 [M]+ (292.1482 calcd for C15H21O5B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; for 24h;Inert atmosphere; Reflux; | General procedure: Under argon atmosphere, a solution of 16 (71.2 mg, 0.291 mmol) and 10 (70.8 mg, 0.268 mmol) in dioxane (2 mL) was added to [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (22.1 mg, 0.027 mmol), and tripotassium phosphate (175 mg, 0.824 mmol) at room temperature. After being refluxed for 24 h, the reaction mixture was evaporated. The residue was chromatographed over silica gel eluted by hexane-EtOAc (9:1) to give 17 (75.4 mg, 0.249 mmol, 93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.25h;Microwave irradiation; | Methyl 2-(3-(2-(((4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyl-2-oxooxazolidin-3-yl)methyl)-4,4-dimethylcyclohex-1-enyl)-4-methoxyphenyl)acetate As shown in reaction scheme 4, pinacolato compound was synthesized. The obtained pinacolato compound (0.1 g, 0.33 mmol), Compound 9 (0.17 g, 0.167 mmol), palladium catalyst (10 mg, 0.02 mmol) and sodium carbonate (70 mg, 0.65 mmol) were dissolved in dimethoxyethane/water (5 mL). The obtained solution was refluxed with stirring in microvessel at 120 C. for 15 minutes. After the completion of the reaction, the reaction was quenched with saturated ammonium chloride solution. The reaction product was extracted with ethyl acetate, washed with brine, dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was separated by MPLC (12 g silica, 1:1=Hexane/EtOAc), thus obtaining Compound 133 (91 mg, 45%) as brown oil. 1H NMR (400 MHz, CDCl3); 1:1 atropisomer mixture; δ7.85 (s, 1H), 7.76 (d, J=7.0, 2H), 7.09-7.13 (m, 1H), 6.76-6.93 (m, 2H), 5.61 (d, J=8.1, 0.5H), 5.55 (d, J=8.0, 0.5H), 3.90-4.03 (m, 2H), 3.75 (d, J=7.3, 3H), 3.64 (d, J=38.0, 3H), 3.41-3.68 (m, 2H), 3.41-3.68 (m, 1H), 2.04-2.53 (m, 2H), 1.89-1.98 (m, 2H), 1.42-1.54 (m, 2H), 1.01-1.04 (m, 6H), 0.33-0.37 (m, 3H). MS (ESI) m/z 615 (M++H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; | General procedure: Compounds II (200-1000 mg) were mixed with the selected boronic acid (1.2 eq), fine powdered K2CO3 (3 eq), Pd(PPh3)4 (0.01 eq) and 1,4-dioxane/water (1/1 by vol.%, 4-8 mL). The reaction was then stirred at 80 C for 2-5 h under nitrogen atmosphere.The solvent was removed and the product was diluted with water(25-50 mL) and extracted with Et2O or EtOAc (25-100 mL), the water phase was extracted with more diethyl ether or EtOAc (2 x 25 mL). The combined organic phases were washed with saturated aq NaCl solution (25 mL), dried over anhydrous Na2SO4,filtered and concentrated in vacuo. Purification was performed as specified for each individual compound. 4.7.32 Methyl (R)-4-methoxy-3-(4-((1-phenylethyl)amino)thieno[2,3-d]pyrimidin-6-yl)benzoate (34b) fx42 Compound 34b was prepared as described in Section 4.7 , starting with compound IIb (123 mg, 0.368 mmol) and 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (179 mg, 0.613 mmol). The crude product was purified using silica-gel column chromatography (EtOAc/n-pentane, 3/2), Rf = 0.21. This gave 124 mg (0.296 mmol, 80%) of 34b as a crystalline white solid, mp. 152-153 C; HPLC purity: 99%, tR = 25.8 min; [α]D20 = -379.6 (c 1.01, DMSO); 1H NMR (600 MHz, DMSO-d6) δ: 8.40-8.38 (m, 1H), 8.38-8.34 (m, 1H), 8.36 (s, 1H), 8.29 (s, 1H), 8.01-7.98 (m, 1H), 7.46-7.42 (m, 2H), 7.36-7.30 (m, 3H), 7.25-7.20 (m, 1H), 5.59-5.50 (m, 1H), 4.05 (s, 3H), 3.89 (s, 3H), 1.59 (d, J = 7.0, 3H); 13C NMR (150 MHz, DMSO-d6) δ: 165.9, 165.7, 158.8, 155.7, 153.9, 144.7, 132.5, 130.9, 128.6, 128.3 (2C), 126.7, 126.1 (2C), 122.4, 122.0, 117.5, 115.9, 112.6, 56.4, 52.1, 49.0, 22.5; IR (neat, cm-1): 3358, 3271, 2970, 2944, 1716, 1578, 1511, 1267, 764, 699; HRMS (APCI/ASAP, m/z) found 420.1378, (calcd. for C23H22N3O3S, 420.1382, [M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; dichloro bis(acetonitrile) palladium(II); triethylamine; In 1,4-dioxane; at 80℃;Inert atmosphere; | General procedure: The target compound was prepared as described in Section 4.6,starting with methyl 3-bromo-4-methoxybenzoate (999 mg, 4.07 mmol). The crude product was purified by crystallization from Et2O (50 mL) to yield 617 mg (2.12 mmol, 52%) of the desiredcompound as white crystals; General procedure for palladium catalysed boronylation The methyl benzoate (200-1500 mg), PdCl2(CH3CN)2 (0.02 eq) and SPhos (0.08 eq) were added to a pressure tube. Then, 1,4-dioxane (0.5-3.5 mL) and Et3N (0.5-2 mL) were added under N2 atmosphere, followed by dropwise addition of HBpin (1.5 eq) while stirring under N2 atmosphere. The reaction mixture was heated to 80 C and stirred for 5-20 h. After cooling to rt, the reaction mixture was filtered through a Celite pad. If further purification was performed, it is specified in each specific example. |
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