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. : | 63349-52-0 | MDL No. : | MFCD09752980 |
Formula : | C9H9IO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | IYIVBGQBEMSRLO-UHFFFAOYSA-N |
M.W : | 276.07 | Pubchem ID : | 10378700 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
98% | With hydrogenchloride; In 1,4-dioxane; at 20℃; for 24h; | To a stirred solution of 4-iodophenylacetic acid (5.0 g, 19.1 mmol) in MeOH (200 mL) was added 4N hydrochloric acid in dioxane (10 mL). The reaction mixture was stirred for 24 h at room temperature and then the solvent was removed under reduced pressure to give the title compound (5.17 g, 98% yield), which was used without further purification. |
98% | With hydrogenchloride; In 1,4-dioxane; at 20℃; for 24h; | Preparation 38 Methyl 4-Iodophenylacetate To a stirred solution of 4-iodophenylacetic acid (5.0 g, 19.1 mmol) in MeOH (200 mL) was added 4N hydrochloric acid in dioxane (10 mL). The reaction mixture was stirred for 24 h at room temperature and then the solvent was removed under reduced pressure to give the title compound (5.17 g, 98% yield), which was used without further purification. |
98% | With hydrogenchloride; In 1,4-dioxane; at 20℃; for 24h; | To a stirred solution of 4-iodophenylacetic acid (5.0 g, 19.1 mmol) in MeOH (200 mL) was added 4N hydrochloric acid in dioxane (10 mL). The reaction mixture was stirred for 24 h at room temperature and then the solvent was removed under reduced pressure to give the title compound (5.17 g, 98% yield), which was used without further purification. |
98% | hydrogenchloride; In 1,4-dioxane; at 20℃; for 24h; | To a stirred solution of 4-iodophenylacetic acid (5.0 g, 19.1 mmol) in MeOH (200 mL) was added 4N hydrochloric acid in dioxane (10 mL). The reaction mixture was stirred for 24 h at room temperature and then the solvent was removed under reduced pressure to give the title compound (5.17 g, 98% yield), which was used without further purification. |
98% | With hydrogenchloride; In 1,4-dioxane; at 20℃; for 24h; | To a stirred solution of 4-iodophenylacetic acid (5.0 g, 19.1 mmol) in MEOH (200 mL) was added 4N hydrochloric acid in dioxane (10 mL). The reaction mixture was stirred for 24 h at room temperature and then the solvent was removed under reduced pressure to give the title compound (5.17 g, 98% yield), which was used without further purification. |
93% | With thionyl chloride; at 0 - 20℃; for 1h; | Methyl (4-iodophenyl)acetate (13).; To a solution of <strong>[1798-06-7](4-iodophenyl)acetic acid</strong> (12) (15.0 g, 57.0 mmol) in dry methanol (50 mL) was added SOCl2 (20.7 mL, 285 mmol, 5 equiv) drop wise at 00C. After stirring for 1 h at room temperature, the solvent was removed under reduced pressure and the residue dissolved in Et2O (400 mL). The organic phase was subsequently washed with saturated aqueous NaHCO3 (400 mL), saturated aqueous NH4Cl (400 mL) and brine (400 mL) and dried over MgSO4. Concentration under reduced pressure gave 13 (14.7 g, 93%). Rf=O.57 (EtOAc/hexane, 1 :4); 1H NMR (360 MHz, CDCl3) δ 7.65 (d, J=8.3 Hz, 2H), 7.03 (d, J=8.3 Hz, 2H), 3.69 (s, 3H), 3.56 (s, 3H); 13C NMR (90 MHz, CDCl3) δ 171.3, 137.6, 133.5, 131.2, 92.5, 52.0, 40.5. |
90% | With tert.-butylnitrite; at 40℃; for 48h; | Add compound 1z (0.5 mmol, 131.1 mg) and methanol containing 40 mol% tert-butyl nitrite to the reaction tube; then react for 48 hours at 40C in air; after the reaction, add sodium thiosulfate and stir. After quenching, using a rotary evaporator to remove the solvent, silica gel adsorption, and finally column chromatography with a mixed solvent of ethyl acetate and petroleum ether to obtain the product 3z, the yield is 90% |
86% | With thionyl chloride; at 20℃; for 36h; | A solution of 5 g (19 mmol) of [(4-IODO-PHENYL)-ACETIC ACID] in 50 mL of methanol [(MEOH)] was added dropwise 3.5 mL [(48] mmol) of [THIENYL] [CHLORIDE (SOCL2),] and the resulting mixture was stirred at rt for 36 h, after which time analysis by thin layer chromatography (TLC) indicated product formation. The mixture was concentrated to give 4.5 g [(86%] yield) of (4-iodo-phenyl)-acetic acid methyl ester as a pale beige oil as indicated by H NMR. A solution of 2. 88 mL (20.5 mmol) [OF DIISOPROPYLAMINE (IPR2NH)] in 50 mL of tetrahydrofuran [(THF)] was flushed with argon and cooled [TO-78 C.] To this solution was added dropwise 8.2 mL (20.5 mmol) [OF N-BUTYLLITHIUM (NBULI)] 2. 5 M solution in hexane, and the resulting mixture was stirred at-78 [C] for 20 min, after which time a solution of 4.5 g (16.3 mmol) of [(4-IODO-PHENYL)-ACETIC ACID METHYL ESTER] in 25 mL of THF was added dropwise. The mixture was allowed to warm up to rt for 40 min, then it was cooled again [TO-78 C,] and 2.62 mL (19.6 mmol) [OF CYCLOHEXANECARBONYL CHLORIDE] was added dropwise, and the resulting mixture was allowed to warm up to rt, and stirred at rt overnight under argon. The reaction mixture was quenched on ice by the addition of saturated ammonium chloride solution, and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over sodium sulfate and concentrated to give 7 g of a burgundy oil which was chromatographed on silica gel (Biotage; 10% ethyl acetate in hexane) to afford 5.06 g [(80%] yield) of desired [3-CYCLOHEXYL-2-(4-IODO-PHE72YL)-3-OXO-PROPIONIC ACID METHYL ESTER AS] a pale yellow solid as indicated [BY 1HNMR] (1: 2.6 keto: enol ratio). LC-MS-calcd for C16Hl9IO3 [[M++H] +] : 387.04, found: 387.0. According to a modified literature procedure (Collins, [1.] et al [J. MED. CHENA.] 2002, 45, 1887-1900) a solution of 5.06 g (13.1 mmol) of 3-cyclohexyl-2-(4-iodo-phenyl)-3-oxo- [PROPIONIC ACID METHYL ESTER] in 80 mL of dimethylsulfoxide (DMSO) was added a solution of 1.53 g (26.2 mmol) of sodium chloride (NaCI) in 5.8 mL of water (H2O), and the resulting mixture was heated at [150 C] for 3 h during which time a white solid formed. The reaction mixture was cooled to rt, poured into 500 mL of water, and extracted thoroughly with ethyl acetate. The combined organic extracts were washed with water (3 times), brine, dried over sodium sulfate and concentrated to give 4.13 g (96% yield) of desired 1-cyclohexyl-2- (4-iodo- phenyl)-ethanone as a yellow solid as indicated by 1H NMR (containing small traces of impurities). The product was used without any further purification in the next step. According to a modified literature procedure (Wasserman, H. H.; Ives, J. L. [J.] Org. Chem. 1985, 50, 3573-3580) a solution of 4.13 g (12.6 mmol) of [1-CYCLOHEXYL-2- (4-IODO-] [PHENYL)-ETHANONE] in 20 mL of toluene was flushed with argon. To this solution was added 2.7 mL (17.6 mmol) [OF METHOXY BIS (DIMETHYLAMINOQ7WLETHA7LE,] and the resulting mixture was stirred at 70C under argon overnight. The reaction mixture was concentrated to give 5.07 g of crude 1-cyclohexyl-3-dimethylamino-2-(4-iodo-phenyl)-propenone as indicated [BY'H NMR] (containing traces of starting material). The product was used without any further purification in the next step. A solution of 2.55 g (6.32 mmol max) of crude 1-cyclohexyl-3-dimethylamino-2-(4- [IODO-PHEENYL)-PROPENONE,] and 0.98 g (6.32 mmol) [OF 5-AFNINO-IH-PYRAZOLE-4-CARBOXYLIC ACID] ethyl ester in 30 mL of acetic acid [(HOAC)] was heated at reflux for 66 h, during which time a precipitate formed. The precipitate was filtered off and discarded, and the acetic acid filtrate was concentrated to a solid residue, which was washed with 1: 1 ethyl acetate: hexane and dried to give 1.67 g (55% yield) of 7-cyclohexyl-6-(4-iodo-phenyl)-pyrazolo[1,5-a]pyrimidine-3- carboxylic acid ethyl ester as a pale yellow [SOLID.'H] NMR (CDC13) [5] 8.57 (s, [1H),] 8. 53 (s, 1H), 7.86-7. 83 (d, J= 8.4 Hz, 2H), 7.1-7. 06 (d, J= 8.4 Hz, 2H), 4.46 (q, 2H, J= 7.2 Hz), 3.31- 3.21 [(M,] 1H), 2.62-2. 41 [(M,] 2H), 1.87-1. 82 [(M,] 2H), 1.74-1. 66 [(IN,] 3H), 1.44 (t, 3H, J= 7.2 Hz), 1.41-1. 21 [(M,] 3H). A solution of 1.66 g (4.1 mmol max) of crude 1-cyclohexyl-3-dimethylamino-2-(4-iodo- [PHENYL)-PROPENONE,] and 0.44 g (4.1 mmol) [OF 5-AMI7LO-LH-PYRAZOLE-4-CARBONITRILE IN] 20 mL of acetic acid [(HOAC)] was heated at reflux for [66 H,] during which time a finely dispersed precipitate formed. Since all attempts to filter off the precipitate were unsuccessful, the reaction mixture was concentrated to give a brown residue which was chromatographed on silica gel (Biotage; 2% ethyl acetate in dichloromethane) to afford 1.09 g (62% yield) of 7- cyclohexyl-6-(4-iodo-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonitrile as a yellow solid NMR (CDC13) [6] 8.49 (s, 1H), 8.39 (s, 1H), 7.88-7. 86 (d, J= 8.4 Hz, 2H), 7.07-7. 05 (d, J= 8.4 Hz, [2H),] 4.13 (q, 2H, J= 7.2 Hz), 3.28-3. 21 [(M,] 1H), 2.59-2. 47 [(M,] 2H), 1.87-1. 8... |
With sulfuric acid; at 85℃; for 16h;Inert atmosphere; | A vessel was charged with Compound Q21A (10 g, 38.1 mmol, 1.00 eq ) in MeOH (60 mL). H2SO4 (3.74 g, 38.1 mmol, 2.03 mL, 1.00 eq ) was added to the mixture under N2. The reaction was stirred at 85 C under N2 for 16 h. The reaction was concentrated under reduced pressure to give a residue. H2O (70 mL) was added, and then reaction was extracted with EtOAc (70, 50, 30 mL). The combined organic phases were washed with saturated aq NaHCCh (70, 50mL). The final organic phase was concentrated under reduced pressure to give Compound Q21B. NMR (400 MHz, CDCh) d 7.65 (d, J= 8.4 Hz, 2H), 7.04 (d, J= 8.4 Hz, 2H), 3.70 (s, 3H), 3.57 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(l) iodide;bis-triphenylphosphine-palladium(II) chloride; In diethylamine; at 20℃; for 17h; | To a stirred solution of the product of Preparation 55 (4.5 g, 16.3 mmol) in diethylamine (100 mL) was added but-3-yn-1-ol (1.9 mL, 32.6 mmol), Pd(PPh3)2Cl2 (500 mg, 1.63 mmol) and CuI (154 mg, 0.815 mmol) and resulting mixture was stirred for 17 h at room temperature. The solvent was then removed under reduced pressure and the residue was dissolved in diethyl ether (200 mL) and this solution was filtered to remove salts. The solvent was then removed under reduced pressure and the crude product was purified by silica gel chromatography (60% EtOAc/Hexane) to afford the title intermediate (3.03 g, 91% yield). |
91% | bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In diethylamine; at 20℃; for 17h; | Preparation 84 [0896] Methyl [4-(4-Hydroxybut-1-ynyl)phenyl]acetate [0897] To a stirred solution of the product of Preparation 83 (4.5 g, 16.3 mmol) in diethylamine (100 mL) was added but-3-yn-1-ol (1.9 mL, 32.6 mmol), Pd(PPh3)2Cl2 (500 mg, 1.63 mmol) and CuI (154 mg, 0.815 mmol) and resulting mixture was stirred for 17 h at room temperature. The solvent was then removed under reduced pressure and the residue was dissolved in diethyl ether (200 mL) and this solution was filtered to remove salts. The solvent was then removed under reduced pressure and the crude product was purified by silica gel chromatography (60% EtOAc/Hexane) to afford the title intermediate (3.03 g, 91% yield). |
91% | With copper(l) iodide; diethylamine;bis-triphenylphosphine-palladium(II) chloride; at 20℃; for 17h; | Preparation 39 Methyl [4-(4-Hydroxybut-1-ynyl)phenyl]acetate To a stirred solution of the product of Preparation 38 (4.5 g, 16.3 mmol) in diethylamine (100 mL) was added but-3-yn-1-ol (1.9 mL, 32.6 mmol), Pd(PPh3)2Cl2 (500 mg, 1.63 mmol) and CuI (154 mg, 0.815 mmol) and resulting mixture was stirred for 17 h at room temperature. The solvent was then removed under reduced pressure and the residue was dissolved in diethyl ether (200 mL) and this solution was filtered to remove salts. The solvent was then removed under reduced pressure and the crude product was purified by silica gel chromatography (60% EtOAc/Hexane) to afford the title intermediate (3.03 g, 91% yield). |
91% | With copper(l) iodide; diethylamine;bis-triphenylphosphine-palladium(II) chloride; at 20℃; for 17h; | To a stirred solution of the product of Preparation 19 (4.5 g, 16.3 mmol) in diethylamine (100 mL) was added but-3-yn-1-ol (1.9 mL, 32.6 mmol), Pd(PPh3)2Cl2 (500 mg, 1.63 mmol) and CuI (154 mg, 0.815 mmol) and resulting mixture was stirred for 17 h at room temperature. The solvent was then removed under reduced pressure and the residue was dissolved in diethyl ether (200 mL) and this solution was filtered to remove salts. The solvent was then removed under reduced pressure and the crude product was purified by silica gel chromatography (60% EtOAc/Hexane) to afford the title intermediate (3.03 g, 91% yield). |
91% | bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In diethylamine; at 20℃; for 17h; | To a stirred solution of the product of Preparation 17 (4.5 g, 16.3 mmol) in diethylamine (100 mL) was added but-3-yn-l-ol (1.9 mL, 32.6 mmol), Pd(PPh3)2Cl2 (500 mg, 1.63 mmol) and Cul (154 mg, 0.815 mmol) and resulting mixture was stirred for 17 h at room temperature. The solvent was then removed under reduced pressure and the residue was dissolved in diethyl ether (200 mL) and this solution was filtered to remove salts. The solvent was then removed under reduced pressure and the crude product was purified by silica gel chromatography (60 % EtOAc/Hexane) to afford the title intermediate (3.03 g, 91% yield). |
91% | With copper(l) iodide;bis-triphenylphosphine-palladium(II) chloride; In diethylamine; at 20℃; for 17h; | To a stirred solution of the product of Preparation 70 (4.5 g, 16.3 mmol) in DIETHYLAMINE (100 mL) was added but-3-yn-1-ol (1.9 mL, 32.6 MMOL), Pd (PPH3) 2CL2 (500 mg, 1.63 mmol) and Cul (154 mg, 0. 815 mmol) and resulting mixture was stirred for 17 h at room temperature. The solvent was then removed under reduced pressure and the residue was dissolved in diethyl ether (200 mL) and this solution was filtered to remove salts. The solvent was then removed under reduced pressure and the crude product was purified by silica gel chromatography (60 % EtOAc/Hexane) to afford the title intermediate (3.03 g, 91% yield). |
82% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diethylamine; In tetrahydrofuran; at 20℃; for 3h;Inert atmosphere; Reflux; | Step 1. Methyl 2-(4-(4-hydroxybut-1-ynyl)phenyl)acetate (53) To a stirred degassed solution of 3-butyn-1-ol (1.587 g, 22.64 mmol) and <strong>[63349-52-0]methyl 2-(4-iodophenyl)acetate</strong> (19) (5.00 g, 18.11 mmol) in THF (50 mL) at rt under nitrogen were added CuI (172 mg, 0.91 mmol), Pd(PPh3)4 (523 mg, 0.45 mmol) and diethylamine (5.64 ml, 54.3 mmol). The reaction mixture was stirred at rt for 3 h, heated to reflux overnight, then cooled to rt, diluted with AcOEt, successively washed with water, a saturated aqueous solution of ammonium chloride, water and brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by Biotage (Snap 100 g cartridge; AcOEt/hexanes: 5/95 to 40/60 over 30 CV, 254 nm for wavelength collection), to afford the title compound 53 (3.23 g, 14.80 mmol, 82%) as an orange sticky oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.7% | General Procedure A: Methel-2-(4-iodophenvl . propionate (Reagent 1); A stirred, cooled (78C) solution of methyl-4-iodophenyl acetate (described in US 6,252, 090, incorporated herein by reference; 2.77g, lOmmol) in anhydrous tetrahydrofuran (20mL) was treated with a 1. 5M solution of lithium diisopropyl amide in tetrahydrofuran and cyclohexane (8mL, 12mmol). The reaction mixture was allowed to warm to 0C over 40 minutes, cooled again to-78C and treated with methyl iodide (0. 75mL, 12mmol). The reaction mixture was allowed to warm to room temperature over lh. It was then quenched with saturated aqueous ammonium chloride solution, diluted with water and extracted with diethyl ether. The combined organic phase was washed with brine (xl), dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a yellow oil (2.7g, 92.7%). 'H NMR (300 MHz, CDC13) : 8 7.66 (d, 2H, J= 8. 5Hz), 7.06 (d, 2H, J= 8. 5Hz), 3.70-3. 66 (m, 1H), 3.67 (s, 3H), 1.49 (d, 3H, J= 7. 0HZ). | |
70% | With acetic acid; In tetrahydrofuran; hexane; | Part G: Preparation of Methyl+-2-(4-iodophenyl)propionate. To a solution of <strong>[63349-52-0]methyl 4-iodophenylacetate</strong> (1.0 g, 3.62 mmol) in dry THF (10 mL) was added sodium hydride (0.095 g, 3.96 mmol, 80% suspension), stirring continued at 5 C. for 30 minutes, followed by the addition of iodomethane (0.68 g, 4.8 mmol). After stirring for 2 hours at room temperature, additional iodomethane (0.46 g, 3.2 mmol) was added, and the reaction mixture was stirred at room temperature overnight for 16 hours. Acetic acid (0.2 mL) was added, and the reaction mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc (30 mL) and 5% citric acid (25 mL). The organic phase was washed with water (2*20 mL), dried (Na2 SO4), filtered and concentrated. The resulting substance was purified by silica gel flash column chromatography eluding with 20% EtOAc in hexane to give methyl+-2-(4-iodophenyl)propionate (0.7 g, 70%) as a pale yellow liquid. 1 H-NMR (CDCl3) δ: 7.64 (d, 2H, J=8.4 Hz), 7.03 (2H, J=8.4 Hz), 3.66 (m over s, 4H), 1.46 (d, 3H, J=7.2 Hz); FAB-MS m/z=291 (M+H); HRMS calcd for C10 H12 IO2 (M+H) 290.9882, found 290.9861. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In acetonitrile; at 0 - 20℃; for 3.5h; | Methyl 2-(4-(2-(trimethylsilyl)ethynyl)phenyl)acetate (14).; To a solution of methyl (4-iodophenyl)acetate (13) (12.8 g, 45 mmol, 1.0 equiv), trimethylsilyl-acetylene (9.30 mL. 67.5 mmol, 1.5 equiv) and TEA (14.9 mL, 108 mmol, 2.4 equiv) in dryCH3CN (120 mL) at 00C was added Pd(PPh3)4 (3.6 g, 3.15 mmol, 0.07 equiv) and CuI (6.00 g, 31.5 mmol, 0.7 equiv). After stirring for 30 min at 00C and 3 h at room temperature, the mixture was filtered through a short column of silica using EtOAc/hexane (1 :1) as eluent. The solvent was removed under reduced pressure and the residue purified by flash chromatography on silica gel (gradient EtOAc/hexane 1 :80→l :20) to yield 14 (10.3 g, 93%) as pale yellow crystals. Rf=Q.21 (EtOAc/hexane, 1 :10); mp 55-58C; 1H NMR (360 MHz, CDCl3) δ 1 Al (d, J=8.4 Hz, 2H), 7.21 (d, J=8.5 Hz52H), 3.68 (s, 3H), 3.61 (s, 2H), 0.25 (s, 9H); 13C NMR (90 <n="22"/>MHz, CDCl3) δ 171.4, 134.3, 132.0 (2C), 129.1 (2C), 122.0, 104.7, 94.2, 52.0, 41.0, - 0.0 (3C); HRMS (EI) calcd for C14Hi8O2Si 246.10761; found 246.10744. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 72h; | Part B. To a THF (100 mL) solution containing sodium hydride (9.5 g, 0.23 mol) at 0 C was added dropwise crudemethyl- <strong>[63349-52-0](4-iodo-phenyl)-acetic acid methyl ester</strong> (21 g, 79 mmol, from Part A in THF (50 mL). After the addition was complete, methyl iodide (11.4 mL, 0.18 mol) in THF (20 mL) was added and the reaction was stirred 72h at rt. The reaction mixture was quenched with ice water followed by extraction with EtOAc. Drying withNa2SO4 afforded 27 g of a crude mixture of two products. Purification by chromatography on silica gel (10: 1 hexanes/ethyl acetate) afforded 5 g pure methyl2- (4-iodophenyl)-2-methyl propronate and 10 g mixture of the desired ester and2- (4- iodophenyl)-2-methylproprionitrile. 1H NMR for methyl 2- (4-iodophenyl) -2-methyl propronate(CDCl3) 8 7.65 (d,J = 8.5, 2H), 7.09 (d,J = 8.8 Hz, 2H), 3.64 (s, 3H), 1.54 (s, 6H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Part A. To 4-iodobenzylbromide (25 g, 84 mmol) in boiling EtOH (100 mL) was added potassium cyanide (8.2 g, 126 mmol) through the condenser. The reaction was heated 24h, then <Desc/Clms Page number 367>cooled and EtOH removed. The aqueous layer was extracted with EtOAc and dried(Na2SO4) to afford crude 4- iodobenzylnitrile. The 4-iodobenzylnitrile was first treated with HC1 gas in MeOH to afford conversion to the ester. The mixture was concentrated in vacuo and treated with MeOH (4.7 mL) and chlorotrimethylsilane (10.7 mL) at50 C for 4h. The reaction was cooled and quenched withH20 (3.5 mL). Dichloromethane (150 mL) was added followed byNa2CO3 (8.9 g) and the mixture was stirred at room temperature forlh. The organics were separated and dried(Na2SO4), filtered, and concentrated to afford 21 g crude (4-iodo-phenyl) -acetic acid methyl ester. 1H NMR(CDC13) a 7.66 (d,J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 3.69 (s, 3H), 3.56 (s, 2H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogenchloride; In methanol; water; at 20℃; for 24h; | Preparation 83 methyl 4-Iodophenylacetate To a stirred solution of 4-iodophenylacetic acid (5.0 g, 19.1 mmol) in MeOH (200 ML) was added 4N hydrochloric acid in dioxane (10 ML).The reaction mixture was stirred for 24 h at room temperature and then the solvent was removed under reduced pressure to give the title compound (5.17 g, 98% yield), which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine;dichlorobis(triphenylphosphine)palladium[II]; In hexane; | {4-[8-Formyl-2,2,4,4-tetramethyl chroman-6-ylethynyl]-phenyl}-acetic acid methyl ester (Compound 45) Following general procedure J and using 6-ethynyl-2,2,4,4-tetramethyl chroman-8-carbaldehyde (Compound 44, 0.39 g, 1.61 mmol), 4-iodo phenyl acetic acid methyl ester (0.444 g, 1.61 mmol), triethyl amine (10 mL), copper(I)iodide (0.025 g, 0.13 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.090 g, 0.13 mmol) followed by flash column chromatography over silica gel (230-400 mesh) using 5-20% ethyl acetate in hexane as the eluent the title compound was obtained as an oil (0.5 g, 80%). 1H NMR (300 MHz, CDCl3): δ10.42 (s, 1H), 7.81 (d, 1H, J=2.1 Hz), 7.64 (d, 1H, J=2.1 Hz), 7.45 (d, 2H, J=8.3 Hz), 7.24 (d, 2H, J=8.3 Hz), 3.68 (s, 3H), 3.62 (s, 2H), 1.88 (s, 2H), 1.41 (s, 6H), 1.37 (s, 6H). |
80% | With triethylamine;dichlorobis(triphenylphosphine)palladium[II]; In hexane; | {4-[8-Formyl-2,2,4,4-tetramethyl chroman-6-ylethynyl]-phenyl}-acetic acid methyl ester (Compound 45) Following general procedure J and using 6-ethynyl-2,2,4,4-tetramethyl chroman-8-carbaldehyde (Compound 44, 0.39 g, 1.61 mmol), 4-iodo phenyl acetic acid methyl ester (0.444 g, 1.61 mmol), triethyl amine (10 mL), copper(I)iodide (0.025 g, 0.13 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.090 g, 0.13 mmol) followed by flash column chromatography over silica gel (230-400 mesh) using 5-20% ethyl acetate in hexane as the eluent the title compound was obtained as an oil (0.5 g, 80%). 1H NMR (300 MHz, CDCl3): δ 10.42 (s, 1H), 7.81 (d, 1H, J=2.1 Hz), 7.64 (d, 1H, J=2.1 Hz), 7.45 (d, 2H, J=8.3 Hz), 7.24 (d, 2H, J=8.3 Hz), 3.68 (s, 3H), 3.62 (s, 2H), 1.88 (s, 2H), 1.41 (s, 6H), 1.37 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
140.0 mg (78%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-methoxycyclopropyl)-phenylethynyl]-phenyl}-acetate (Compound 68, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-methoxycyclopropyl)-benzene (Intermediate 61, 120.0 mg, 0.56 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 154.0 mg, 0.56 mmol) in triethyl amine (6 mL) was treated with copper(I)iodide (35.0 mg, 0.19 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (130 mg, 0.19 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-8% EtOAc-hexanes) afforded 140.0 mg (78%) of the title compound as an orange solid. 1H NMR (CDCl3) δ: 7.50 (4H, d, J=8.1 Hz), 7.28 (4H, d, J=8.1 Hz), 3.76 (3H, s), 3.64 (2H, s), 3.25 (3H, s), 1.22 (2H, m), 0.99 (2H, m). |
140.0 mg (78%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-methoxycyclopropyl)-phenylethynyl]-phenyl }-acetate (Compound 68, general Formula 2) Using General Procedure F; 1-ethynyl-4-(1-methoxycyclopropyl)benzene (Intermediate 61, 120.0 mg, 0.56 mmol) and methyl-(4-iodophenyl)acetate (Reagent B, 154.0 mg, 0.56 mmol) in triethyl amine (6 mL) was treated with copper(I)iodide (35.0 mg, 0.19 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (130 mg, 0.19 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-8% EtOAc-hexanes) afforded 140.0 mg (78%) of the title compound as an orange solid. 1H NMR (CDCl3) δ: 7.50 (4H, d, J=8.1 Hz), 7.28 (4H, d, J=8.1 Hz), 3.76 (3H, s), 3.64 (2H, s), 3.25 (3H, s), 1.22 (2H, m), 0.99 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
110.0 mg (70%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-isopropoxycyclopropyl)-phenylethynyl]-phenyl}-acetate (Compound 72, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-isopropoxycyclopropyl)-benzene (Intermediate 66, 95.0 mg, 0.45 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 131.0 mg, 0.45 mmol) in triethylamine (6 mL) was treated with copper(I)iodide (30.0 mg, 0.16 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (111 mg, 0.16 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-8% EtOAc-hexanes) afforded 110.0 mg (70%) of the title compound as an orange oil. 1H NMR (CDCl3) δ: 7.20 (4H), 7.08 (2H, d, J=7.0 Hz), 6.97 (2H, d, J=7.9 Hz), 3.45 (1H, septet, J=6.2 Hz), 3.41 (3H, s), 3.35 (2H, s), 0.91 (2H, m), 0.79 (6H, d, J=6.2 Hz), 0.68 (2H, m). |
110.0 mg (70%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-isopropoxycyclopropyl)-phenylethynyl]-phenyl}-acetate (Compound 72, general Formula 2) Using General Procedure F; 1-ethynyl-4-(1-isopropoxycyclopropyl)benzene (Intermediate 66, 95.0 mg, 0.45 mmol) and methyl-(4-iodophenyl)acetate (Reagent B, 131.0 mg, 0.45 mmol) in triethylamine (6 mL) was treated with copper(I)iodide (30.0 mg, 0.16 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (111 mg, 0. 16 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-8% EtOAc-hexanes) afforded 110.0 mg (70%) of the title compound as an orange oil. 1H NMR (CDCl3) δ: 7.20 (4H), 7.08 (2H, d, J=7.0 Hz), 6.97 (2H, d, J=7.9 Hz), 3.45 (1H, septet, J=6.2 Hz), 3.41 (3H, s), 3.35 (2H, s), 0.91 (2H, m), 0.79 (6H, d, J=6.2 Hz), 0.68 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.0 mg (81%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-benzyloxycyclopropyl)-phenylethynyl]-phenyl}-acetate (Compound 76, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-benzyloxycyclopropyl)-benzene (Intermediate 71, 60.0 mg, 0.20 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 66.0 mg, 0.24 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (15.0 mg, 0.08 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (56 mg, 0.08 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-7% EtOAc-hexanes) afforded 64.0 mg (81%) of the title compound as a yellow oil. 1H NMR (CDCl3) δ: 7.52-7.47 (4H, m), 7.37-7.25 (9H, m), 4.44 (2H, s), 3.70 (3H, s), 3.64 (2H, s), 1.32 (2H, m), 1.06 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.0 mg (71%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-benzyloxycyclopropyl)-3-methyl-phenylethynyl]-phenyl}-acetate (Compound 80, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-benzyloxycyclopropyl)-3-methyl-benzene (Intermediate 76, 90.0 mg, 0.34 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 95.0 mg, 0.34 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (22.0 mg, 0.11 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (80 mg, 0.11 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-4% EtOAc-hexanes) afforded 90.0 mg (71%) of the title compound as a pale-yellow oil. 1H NMR (CDCl3) δ: 7.49 (2H, d, J=8.2 Hz), 7.32-7.16 (10H, m), 4.28 (2H, s), 3.70 (3H, s), 3.64 (2H, s), 2.56 (3H, s), 1.22 (2H, m), 0.92 (2H, m). |
90.0 mg (71%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-benzyloxycyclopropyl)-3-methyl-phenylethynyl]-phenyl}-acetate (Compound 80, general Formula 2) Using General Procedure F; 1-ethynyl-4-(1-benzyloxycyclopropyl)-3-methyl-benzene (Intermediate 76, 90.0 mg, 0.34 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 95.0 mg, 0.34 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (22.0 mg, 0.11 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (80 mg, 0.11 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-4% EtOAc-hexanes) afforded 90.0 mg (71%) of the title compound as a pale-yellow oil. 1H NMR (CDCl3) δ: 7.49 (2H, d, J=8.2 Hz), 7.32-7.16 (1 OH, m), 4.28 (2H, s), 3.70 (3H, s), 3.64 (2H, s), 2.56 (3H, s), 1.22 (2H, m), 0.92 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
120.0 mg (71%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-isopropoxycyclopropyl)-3-methyl-phenylethynyl]-phenyl }-acetate (Compound 84, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-isopropoxycyclopropyl)-3-methyl-benzene (Intermediate 81, 100.0 mg, 0.47 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 129.0 mg, 0.45 mmol) in triethylamine (6 mL) was treated with copper(I)iodide (30.0 mg, 0.16 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (110 mg, 0.16 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-4% EtOAc-hexanes) afforded 120.0 mg (71%) of the title compound. 1H NMR (CDCl3) δ: 7.48 (2H, d, J=8.5 Hz), 7.36 (1H, s), 7.29-7.22 (4H, m), 3.70 (3H, s), 3.63 (2H, s), 3.60 (1H, septet, J=6.2 Hz), 2.52 (3H, s), 1.09 (2H, m), 0.97 (6H, d, J=6.2 Hz), 0.86 (2H, m). |
120.0 mg (71%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-isopropoxycyclopropyl)-3-methyl-phenylethynyl]-phenyl}-acetate (Compound 84, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-isopropoxycyclopropyl)-3-methyl-benzene (Intermediate 81, 100.0 mg, 0.47 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 129.0 mg, 0.45 mmol) in triethylamine (6 mL) was treated with copper(I)iodide (30.0 mg, 0.16 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (110 mg, 0.16 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-4% EtOAc-hexanes) afforded 120.0 mg (71%) of the title compound. 1H NMR (CDCl3) δ: 7.48 (2H, d, J=8.5 Hz), 7.36 (1H, s), 7.29-7.22 (4H, m), 3.70 (3H, s), 3.63 (2H, s), 3.60 (1H, septet, J=6.2 Hz), 2.52 (3H, s), 1.09 (2H, m), 0.97 (6H, d, J=6.2 Hz), 0.86 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
130.0 mg (79%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-benzyloxycyclopropyl)-3-ethyl-phenylethynyl]-phenyl }-acetate (Compound 92, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-benzyloxycyclopropyl)-3-ethyl-benzene (Intermediate 90, 107.0 mg, 0.39 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 110.0 mg, 0.39 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (25.0 mg, 0.13 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (91 mg, 0.13 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-4% EtOAc-hexanes) afforded 130.0 mg (79%) of the title compound as a pale-yellow oil. 1H NMR (CDCl3) δ: 7.49 (3H, m), 7.32-7.16 (9H, m), 4.28 (2H, s), 3.71 (3H, s), 3.64 (2H, s), 3.03 (2H, q, J=7.6 Hz), 1.32-1.23 (5H, m), 0.94 (2H, m). |
130.0 mg (79%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-benzyloxycyclopropyl)-3-ethyl-phenylethynyl]-phenyl}-acetate (Compound 92, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-benzyloxycyclopropyl)-3-ethyl-benzene (Intermediate 90, 107.0 mg, 0.39 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 110.0 mg, 0.39 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (25.0 mg, 0.13 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (91 mg, 0.13 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-4% EtOAc-hexanes) afforded 130.0 mg (79%) of the title compound as a pale-yellow oil. 1H NMR (CDCl3) δ: 7.49 (3H, m), 7.32-7.16 (9H, m), 4.28 (2H, s), 3.71 (3H, s), 3.64 (2H, s), 3.03 (2H, q, J=7.6 Hz), 1.32-1.23 (5H, m), 0.94 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
150.0 mg (70%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-isopropoxycyclopropyl)-3-ethyl-phenylethynyl]-phenyl}-acetate (Compound 96, General Formula 2) Using General Procedure F; 1-ethynyl-4-(1-isopropoxycyclopropyl)-3-ethyl-benzene (Intermediate 95, 130.0 mg, 0.57 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 157.0 mg, 0.57 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (36.0 mg, 0.19 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (133 mg, 0.19 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-5% EtOAc-hexanes) afforded 150.0 mg (70%) of the title compound as an orange oil. 1H NMR (CDCl3) δ: 7.50-7.44 (3H, m), 7.27 (4H, m), 3.70 (3H, s), 3.64 (2H, s), 3.62 (1H, septet, J=6.2 Hz), 3.00 (2H, q, J=7.6 Hz), 1.30 (3H, t, J=7.6 Hz), 1.13 (2H, m), 0.97 (6H, d, J=6.2 Hz), 0.87 (2H, m). |
150.0 mg (70%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-isopropoxycyclopropyl)-3-ethyl-phenylethynyl]-phenyl}-acetate (Compound 96, General Formula 2) Using General Procedure F; l-ethynyl-4-(1-isopropoxycyclopropyl)-3-ethyl-benzene (Intermediate 95, 130.0 mg, 0.57 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 157.0 mg, 0.57 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (36.0 mg, 0.19 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (133 mg, 0.19 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-5% EtOAc-hexanes) afforded 150.0 mg (70%) of the title compound as an orange oil. 1H NMR (CDCl3) δ: 7.50-7.44 (3H, m), 7.27 (4H, m), 3.70 (3H, s), 3.64 (2H, s), 3.62 (1H, septet, J=6.2 Hz), 3.00 (2H, q, J=7.6 Hz), 1.30 (3H, t, J=7.6 Hz), 1.13 (2H, m), 0.97 (6H, d, J=6.2 Hz), 0.87 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100.0 mg (72%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-ethoxycyclopropyl)-3-tert-butyl-phenylethynyl]-phenyl}-acetate (Compound 104, General Formula 2) Using General Procedure F; 1-(1-ethoxycyclopropyl)-4-ethynyl-2-tert-butylbenzene (Intermediate 112, 95.0 mg, 0.39 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 108.0 mg, 0.39 mmol) in triethylamine (8 mL) was treated with copper(I)iodide (25.0 mg, 0.13 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (91 mg, 0.13 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-5% EtOAc-hexanes) afforded 100.0 mg (72%) of the title compound. 1H NMR (CDCl3) δ: 7.70 (1H, d, J=1.5 Hz), 7.50 (2H, d, J=7.9 Hz), 7.38 (1H, d, J=7.9 Hz), 7.27 (3H, m), 3.70 (3H, s), 3.64 (2H, s), 3.28 (2H, q, J=7.1 Hz), 1.54 (9H, s), 1.12 (2H, bs), 1.08-1.03 (5H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45.0 mg (25%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl [4-(4-imidazol-1-yl-methyl-3-methyl-phenylethynyl)-phenyl]-acetate (Compound 120, General Formula 6) Using General Procedure F; 1-(4-ethynyl-2-methyl-benzyl)-1H-imidazole (Intermediate 141, 101.0 mg, 0.53 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 145.0 mg, 0.53 mmol) in triethylamine (5 mL) was treated with copper(I)iodide (34.0 mg, 0.18 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (124 mg, 0.18 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (5% MeOH-EtOAc) afforded 45.0 mg (25%) of the title compound as an orange oil. 1H NMR (CDCl3) δ: 7.47 (3H, m), 7.35 (3H, m), 7.27 (3H, m), 6.91 (1H, d, J=7.3 Hz), 5.11 (2H, s), 3.70 (3H, s), 3.64 (2H, s), 2.26 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.0 mg (60%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[3-isopropyl-4-(1-methyl-cyclopropoxymethyl)-phenylethynyl]-phenyl}-acetate (Compound 140, General Formula 6) Using General Procedure F; 4-ethynyl-2-isopropyl-1-(1-methyl-cyclopropoxymethyl)-benzene (Intermediate 166, 78.0 mg, 0.34 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 94.0 mg, 0.34 mmol) in triethylamine (8 mL) was treated with copper(I)iodide (22.0 mg, 0.11 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (79 mg, 0.11 mmol) was added and the reaction mixture was stirred at room temperature for 3.5 hours. Column chromatography (2-5% EtOAc-hexanes) afforded 77.0 mg (60%) of the title compound as a yellow oil. 1H NMR (CDCl3) δ: 7.49 (2H, d, J=8.2 Hz), 7.43 (1H, d, J=1.5 Hz), 7.33-7.24 (4H, m), 4.55 (2H, s), 3.70 (3H, s), 3.63 (2H, s), 3.14 (1H, septet, J=6.8 Hz), 1.47 (3H, s), 1.25 (6H, d, J=6.8 Hz), 0.86 (2H, m), 0.46 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
250.0 mg (75%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl [4-(8,8-dimethyl-5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl-ethynyl)-phenyl]-acetate (Compound 4, General Formula 8) Using General Procedure F; 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-naphthalen-1-one (Intermediate 13, 190.0 mg, 0.96 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 245.0 mg, 0.96 mmol) in triethyl amine (8 mL) was treated with copper(I)iodide (46 mg, 0.24 mmol) and sparged with argon for 15 minutes. Dichlorobis(triphenylphosphine)palladium(II) (168 mg, 0.24 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (10-20% EtOAc-hexanes) afforded 250.0 mg (75%) of the title compound as a pale-yellow solid. 1H NMR (CDCl3) δ: 7.99 (1H, d, J=7.9 Hz), 7.57 (1H, d, J=1.5 Hz), 7.51 (2H, d, J=8.5 Hz), 7.43 (1H, dd, J=1.5, 7.9 Hz), 7.29 (2H, d, J=8.5 Hz), 3.70 (3H, s), 3.65 (2H, s), 2.73 (2H, t, J=7.0 Hz), 2.04 (2H, t, J=7.0 Hz), 1.41 (6H, s). |
250.0 mg (75%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl [4-(8,8-dimethyl-5-oxo-5.6,7,8-tetrahydro-naphthalen-2-yl-ethynyl)-phenyl]-acetate (Compound 4, General Formula 8) Using General Procedure F; 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-naphthalen-1-one (Intermediate 13, 190.0 mg, 0.96 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 245.0 mg, 0.96 mmol) in triethyl amine (8 mL) was treated with copper(I)iodide (46 mg, 0.24 mmol) and sparged with argon for 15 minutes. Dichlorobis(triphenylphosphine)palladium(II) (168 mg, 0.24 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (10-20% EtOAc-hexanes) afforded 250.0 mg (75%) of the title compound as a pale-yellow solid. 1H NMR (CDCl3)δ: 7.99 (1H, d, J=7.9 Hz), 7.57 (1H, d, J=1.5 Hz), 7.51 (2H, d, J=8.5 Hz), 7.43 (1H, dd, J=1.5, 7.9 Hz), 7.29 (2H, d, J=8.5 Hz), 3.70 (3H, s), 3.65 (2H, s), 2.73 (2H, t, J=7.0 Hz), 2.04 (2H, t, J=7.0 Hz), 1.41 (6H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With CuI; triethylamine; In hexane; acetonitrile; | Part A: Preparation of Methyl 4-(4-hydroxy-1-butynyl)phenylacetate. To a solution of butyn-1-ol (0.76 g, 0.11 mol) and <strong>[63349-52-0]methyl 4-iodophenylacetate</strong> (1.5 g, 0.0054 mol) in acetonitrile (10 mL) at 0 C., triethylamine (1.5 mL, 0.01 mol) was added, followed by the addition of bistriphenylphosphine palladium chloride (0.25 g, 0.36 mmol) and CuI (0.025 g). The reaction mixture was stirred at 0 C. under an argon atmosphere for 30 minutes and at room temperature for 3 hours. The dark colored reaction mixture was concentrated under reduced pressure, and the residue was partitioned between 5% citric acid (50 mL) and EtOAc (50 ML). The organic phase was washed with 5% citric acid (3*15 mL), water, dried (Na2 SO4), filtered, and concentrated. The resulting material was purified by silica gel flash column chromatography eluding with 35% EtOAc in hexane to afford methyl 4-(4-hydroxy-1-butynyl)phenylacetate (1 g, 85%) as a dark colored liquid. FAB-MS m/z=219 (M+H), HRMS calcd. for C13 H15 O3 (M+H), 219.1021, found 219.1008. Calcd for C13 H14 O3: C, 71.54, H 6.46; found: C, 71.04, H, 6.41. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In pyridine; water; | EXAMPLE 15 Methyl [p-(phenylthio)phenyl]acetate A solution of 6.9 g of <strong>[63349-52-0]methyl 4-iodophenylacetate</strong> and 4.74 g of cuprous phenylmercaptide in 250 ml of pyridine is heated to reflux and maintained at reflux under Argon for 18 hours. The resulting brown solution is poured into 500 ml of water and extracted with 200 ml of ether. The organic extract is washed with 200 ml each of 10% HCl, saturated NaHCO3, saturated brine and dried over MgSO4. Evaporation of the solvent at reduced pressure affords a brown liquid, which is filtered through aluminum oxide (benzene eluant). The benzene is evaporated and the residue is distilled (128 C at 0.05 mm) to yield the product as a colorless liquid. | |
With hydrogenchloride; In pyridine; water; | EXAMPLE 15 Methyl [p-(phenylthio)phenyl]acetate A solution of 6.9 g of <strong>[63349-52-0]methyl 4-iodophenylacetate</strong> and 4.74 g of cuprous phenylmercaptide in 250 ml of pyridine is heated to reflux and maintained at reflux under Argon for 18 hours. The resulting brown solution is poured into 500 ml of water and extracted with 200 ml of ether. The organic extract is washed with 200 ml each of 10% HCl, saturated NaHCO3, saturated brine and dried over MgSO4. Evaporation of the solvent at reduced pressure affords a brown liquid, which is filtered through aluminum oxide (benzene eluant). The benzene is evaporated and the residue is distilled (128 C. ã 0.05 mm) to yield the product as a colorless liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
140.0 mg (71%) | dichlorobis(triphenylphosphine)palladium[II]; In triethylamine; | Methyl {4-[4-(1-ethoxycyclopropyl)-3-isopropyl-phenylethynyl]-phenyl}-acetate (Compound 100, General Formula 2) Using General Procedure F; 1-(1-ethoxycyclopropyl)-4-ethynyl-2-isopropylbenzene (Intermediate 103, 120.0 mg, 0.52 mmol) and methyl-(4-iodophenyl)-acetate (Reagent B, 150.0 mg, 0.52 mmol) in triethylamine (8 mL) was treated with copper(I)iodide (32.0 mg, 0.17 mmol) and sparged with argon for 5 minutes. Dichlorobis(triphenylphosphine)palladium(II) (121 mg, 0.17 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-5% EtOAc-hexanes) afforded 140.0 mg (71%) of the title compound as a pale-yellow oil. 1H NMR (CDCl3) δ: 7.53 (3H, m), 7.31-7.23 (4H, m), 3.86 (1H, septet, J=6.7 Hz), 3.73 (3H, s), 3.67 (2H, s), 3.33 (2H, q, J=7.0 Hz), 1.30 (6H, d, J=6.7 Hz), 1.15 (2H, m), 1.08 (3H, t, J=7.0 Hz), 0.90 (2H, m). |
Tags: 63349-52-0 synthesis path| 63349-52-0 SDS| 63349-52-0 COA| 63349-52-0 purity| 63349-52-0 application| 63349-52-0 NMR| 63349-52-0 COA| 63349-52-0 structure
[ 502649-73-2 ]
Methyl 2-(3-iodophenyl)acetate
Similarity: 1.00
[ 880134-34-9 ]
Methyl 2-(5-iodo-2-methylphenyl)acetate
Similarity: 0.95
[ 502649-73-2 ]
Methyl 2-(3-iodophenyl)acetate
Similarity: 1.00
[ 502649-73-2 ]
Methyl 2-(3-iodophenyl)acetate
Similarity: 1.00
[ 880134-34-9 ]
Methyl 2-(5-iodo-2-methylphenyl)acetate
Similarity: 0.95
[ 502649-73-2 ]
Methyl 2-(3-iodophenyl)acetate
Similarity: 1.00
[ 502649-73-2 ]
Methyl 2-(3-iodophenyl)acetate
Similarity: 1.00
[ 880134-34-9 ]
Methyl 2-(5-iodo-2-methylphenyl)acetate
Similarity: 0.95
[ 502649-73-2 ]
Methyl 2-(3-iodophenyl)acetate
Similarity: 1.00
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 :