* 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.
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 4, p. 581 - 586
2
[ 104-01-8 ]
[ 531-95-3 ]
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3
[ 104-01-8 ]
[ 491-80-5 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 2000, vol. 4, p. 567 - 570
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4
[ 104-01-8 ]
[ 108-73-6 ]
[ 491-80-5 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1991, # 12, p. 3005 - 3008
5
[ 104-01-8 ]
[ 13435-12-6 ]
[ 7087-68-5 ]
Reference：
[1] Patent: US2003/18193, 2003, A1,
6
[ 104-01-8 ]
[ 4693-91-8 ]
Yield
Reaction Conditions
Operation in experiment
100%
With thionyl chloride In benzene for 1 h; Heating / reflux
16.62g (0.1 mol) of 4-methoxyphenylacetic acid was dissolved in 10ml of benzene before 29ml (0. 2 mol) of thionylchloride was added thereto. Then, the solution was heated and refluxed, and was stirred for one hour. Thionylchloride remaining in the reaction solution and the solvent was condensed to be removed to obtain 4-methoxy-phenyl-acetyl chloride (compound I), a liquid phase product, at a quantitative yield. The product was used without purification.
100%
for 2 h; Reflux
General procedure: A mixture of various carboxylic acids (1.0mmol), an excess of thionyl chrolide (5mL) was refluxed for 2h and concentrated in vacuo to give corresponding acyl chloride (quant).
88%
With thionyl chloride In <i>N</i>-methyl-acetamide; water
(i) 4-Methoxyphenylacetyl chloride Thionyl chloride (200 ml) was added to 4-methoxyphenylacetic acid (78 g, 0.47 mole) followed by one drop of dimethylformamide. The reaction was heated at 65° C. for 4 hours and the solvent was removed under vacuum. The residue was distilled in vacuo (water aspirator) at 135° C. to give the product as a red oil (75.9 g, 88percent).
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Stage #1: With thionyl chloride In dichloromethane at 0 - 20℃; Stage #2: With ammonia In dichloromethane; water
Example 6N-(4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)-2-(4-methoxyphenyl)-acetamidePreparation of the starting material 2-(4-Methoxyphenyl)acetamide. A solution of 2-(4-methoxyphenyl)acetic acid (500 mg, 3.00 mmol) in DCM (30 ml) was added thionyl chloride (0.4 ml, 4.5 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and continued to stirred overnight. Then aqueous ammonia (2 ml) was added to the reaction mixture. The white solid forming was filtered and dried under vacuum to obtained 350 mg (70percent) of 2-(4-methoxyphenyl)acetamide as a white solid.
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13
[ 104-01-8 ]
[ 77287-34-4 ]
[ 6343-93-7 ]
Reference：
[1] Yakugaku Zasshi, 1942, vol. 62, p. 532; engl. Ref. S. 169[2] Chem.Abstr., 1951, p. 2861
Commercially available 4-methoxyphenylacetic acid (16. 6g, 0.1 mol) was dissolved in acetic acid (120 mL) and stirred vigorously at approximately 0 C. A solution of elemental bromine (16.0 g, 0.1 mol) in acetic acid (40 mL) was added dropwise over 45 minutes, ensuring that the mixture did not freeze. The reaction mixture was allowed to warm slowly to room temperature and stir overnight. The mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was collected, washed with water, brine and 5% aqueous NAHS03, filtered and concentrated in vacuo to give 3-bromo-4-methoxyphenylacetic acid (24.24 g, 98%) as a yellow powder.
86.0%
With bromine; acetic acid; at 20℃; for 24h;
To a 500mL round bottom flask was added 4-methoxy-phenylacetic acid (16.6g, 0.1mol), dissolved in acetic acid (150 mL), was added dropwise acetic acid (50 mL) diluted bromine (5.6mL, 0.11mol) at room temperature, dropwise completed, at room temperature 24h, quenched with a solution of sodium sulfite the unreacted bromine, the solvent was evaporated under reduced pressure, (50 mL), suction filtered, the filter cake was washed with water to give the residue in water, drained, and the filter cake was collected and dried to give a white solid after (20.9 g, yield 86.0%).
86.0%
In acetic acid; at 20℃; for 24h;
To a 500mL round bottom flask was added 4-methoxy-phenylacetic acid (16.6g, 0.1mol), dissolved in acetic acid (150 mL), was added dropwise acetic acid (50 mL) diluted bromine (5.6mL, 0.11mol) at room temperature, dropwise completed, at room temperature 24h, quenched with a solution of sodium sulfite the unreacted bromine, the solvent was evaporated under reduced pressure, (50 mL), suction filtered, the filter cake was washed with water to give the residue in water, drained, and the filter cake was collected and dried to give a white solid after (20.9 g, yield 86.0%).
86%
With bromine; In acetic acid; at 20℃; for 24h;
500mL round bottom flask was added 4-methoxy phenylacetic acid (16. 6g, 0. Lmol), with acetic acid (150 mL) was dissolved, was added dropwise acetic acid (50 mL) was diluted bromine (5. 6mL, 0 at room temperature. Llmol ), dropping was completed, the reaction at room temperature for 24h, quenched with a solution of sodium sulfite unreacted bromine complete, the solvent was evaporated under reduced pressure, (50 mL), suction filtered, the filter cake was washed with water to give the residue in water, drained, collected cake and dried to give a white solid (20. 9g, yield 86.0%)
With bromine; acetic acid; at 20℃;Product distribution / selectivity;
(1) Preparation of Compound 139; A?B; To a stirred solution of A (166 g, 1.0 mol) in AcOH (2.0 L) was added bromine (56 mL, 1.1 mol) drop-wise at room temperature. The solution was stirred overnight. When the reaction was completed, the solvent was evaporated off. The residue was extracted with EtOAc, washed with water and concentrated to give 225 g of B.
(5S,8R,13R,15aS)-8-[(S)-2-Amino-3-(4-methoxy-phenyl)-3-oxo-propionylamino]-5-hydroxymethyl-4,7,15-trioxo-tetradecahydro-10,11-dithia-3a,6,14-triaza-cyclopentacyclotetradecene-13-carboxylic acid[ No CAS ]
With sodium hydroxide; nitric acid; acetic anhydride;
Step 1 Methyl 2-(3-Nitro4-methoxyphenyl)acetate An oven-dried 2-L, 3-neck round bottom flask, equipped with a mechanical stir motor, a low-temperature thermometer and an equalizing dropping funnel, was charged with acetic anhydride (631 mL) and subsequently cooled to -78 C. Fuming nitric acid (Baker, 90%, 27 mL) was added dropwise via the dropping funnel protected with a drying tube filled with CaCl2. After addition was completed, the reaction temperature was allowed to warm to 20 C. over 1 h. The reaction mixture was cooled to -78 C. again and added 4-methoxyphenylacetic acid (50 g, 0.28 mol) dropwise via the dropping funnel. After stirring at -50 C. for 1 h., the reaction mixture was allowed to warm to -30 C. over 20 min. and then cooled to -50 C. again. The reaction mixture was quenched with H2O (500 mL) at -50 C. and warmed up to room temperature and stirred for 0.5 h. The reaction mixture was partitioned between CH2Cl2 (500 mL) and H2O. The aqueous layer was extracted with CH2Cl2 (3*500 mL). The combined CH2Cl2 extracts were concentrated in vacuo to give a yellow oil. This was added slowly to a 2 M solution of NaOH (2 L) cooled at 0 C. and stirred at room temperature overnight. The reaction mixture was partitioned between CH2Cl2 (500 mL) and H2O. The aqueous layer was extracted with CH2Cl2 (3*500 mL). The combined CH2Cl2 extracts were stirred with 2 M NaOH solution (1 L) for 1 h. The layers were separated and the organic layer was washed with H2O (500 mL), brine (500 mL), dried over Na2SO4 and filtered. The solvents were removed in vacuo to afford crude product as a light yellow solid (56 g). Purification by recrystallization from MeOH (600 mL) gave product. Yield 48 g (77%).
EXAMPLE 20 7-Chloro-3-(4-hydroxyphenyl)-2(1H)-quinolone 2-Amino-4-chlorobenzyl alcohol (4 g, 25.3 mol) and 4-methoxyphenyl acetic acid (14.0 g, 76.4 mmol) were reacted in a similar manner to that described in Example 19 to give 7-chloro-3-(4-methoxyphenyl)-2(1H)-quinolone; mp 256-257 C. (ethyl acetate).
DIISOPROPYLAMINE (7. 4ml, 52. [8MMOL)] was added to anhydrous THF under argon. The solution was stirred and cooled to-35C in a dry ice/acetone bath and N-butyl lithium (1.6M, 31. 2ml, 50.4mmol) was added via a syringe over 2-3 mins, controlling the exotherm to [BELOW-20C.] After the addition was complete the reaction was cooled to-70C and a solution of 4-methoxyphenylacetic acid (3.89g, [24MMOL)] in THF (48ml) was transferred to the reaction mixture via a cannula, adding the solution dropwise and keeping the temperature below-55C. The reaction was stirred for 10 mins [AT-70C] and then allowed to warm up to [- L5C.] A solution [OF N-METHYL-N-METHOXY-4-FLUOROPHENYLCARBAMOYL] (4. [38G,] 26. [4MMOL)] in THF (48ml) was added via a dropping funnel dropwise, while the reaction mixture exothermed to [0C.] After addition was complete, the reaction was allowed to warm up to room temperature and stirred for 1.5 hours. The reaction was added to a stirred solution of concentrated hydrochloric acid [(13ML)] in water [(250ML),] and was stirred for 10 mins before the addition of ether. The organic layer was separated, washed with water, aqueous sodium bicarbonate and brine and dried (MgS04). The solvent removed in vacuo to give a sticky solid. This was triturated with methanol, and the resultant solid was dried under high vacuum to give a white solid (2.2g). Mp [107-109C] ; NMR [(200MHZ)] 3.78 (3H, s), 4.17 (2H, s), 6.87 (2H, d), 7.13 (4H, m), 8.03 (2H, dd).
Example 6N-(4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)-2-(4-methoxyphenyl)-acetamidePreparation of the starting material 2-(4-Methoxyphenyl)acetamide. A solution of 2-(4-methoxyphenyl)acetic acid (500 mg, 3.00 mmol) in DCM (30 ml) was added thionyl chloride (0.4 ml, 4.5 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and continued to stirred overnight. Then aqueous ammonia (2 ml) was added to the reaction mixture. The white solid forming was filtered and dried under vacuum to obtained 350 mg (70percent) of 2-(4-methoxyphenyl)acetamide as a white solid.
4-(2-{(5-Ethylpyrimidin-2-yl)[4-(trifluoromethoxy)benzyl]amino}-1-methylethyl)phenol; Step 1.; To a 2M solution of LDA in heptane (commercial rade; 66.2 ml) at 0C, under nitrogen, it was added 4-methoxyphenyl acetic acid (5.5 g; 33.09 mmol). After stirring at 0C for 40 minutes it was added iodomethane (13. 18 ml ; 211. 78 mmol). Allowed to warm to rt and stirred additional 30 minutes. The reaction mixture was then added to 200 ml of saturated ammonium chloride. Extracted 3x150 ml of ethyl ether. The aqueous phase was acidified with 1N HCl and extracted 2x150ml with ethyl ether. The latter organic phases were dried over sodium sulfate and concentrated to afford 5. 8 g of an oil which corresponded to a 2.5:1 mixture of 2-(4-methoxyphenyl)-2-methylpropanoic acid (bis-methylation product) to 2- (4-methoxyphenyl)propanoic acid (monomethylation product) which was used in the next step without any further purification.
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; at 0 - 70℃;
Step I: To a stirred solution of 6-bromo-3,4-dihydro-2H-benzo(1,4Joxazine (1.5 g, 7.0 mmol) in dichloromethane - dimethylforrnamide (1:1 mixture. 40 ml) was added 4- methoxyphenyl acetic acid (1.8 g, 10.5 mmol), HOBt (2.4 g, 17.5 mmol), diisopropyiethylamine (4.8 ml, 28 mmol ). EDCI.HCI (3.4 g . 17.5 mmol) at 0 C After 15 rnin, reaction mixture was heated to 70 C for 15 h. quenched by the addition of water. After usual work up, the compound was purified by silica gel column chromatography (10% ethyl acetate in hexane) to furnish 1-(6-bromo-2,3-dihydro-benzo[1.4]oxazin-4-yl)- 2-(4-methoxy-phenyl)-ethanone (1.8 g).1H NMR (400 MHz, CDCI3): delta 3.79 (s, 3H), 3.86 (bs, 4H), 4.14 (bs. 2H): 6.76 (ds J * 8.4 Hz, 1H), 6.86 (d. J « 8.8 Hz. 2H)1 7,16 (d, J * 8.4 Hz: 4H). MS (ES) iWz 364.0 (M+2).
With triethylamine; dicyclohexyl-carbodiimide; In acetonitrile; at 20℃;
To a solution of [4-(methyloxy)phenyl]acetic acid (2.156 g, 12.97 mmol), ethyl 3- amino-1 H-pyrrole-2-carboxylate (2 g, 12.97 mmol) and triethylamine (1.989 mL, 14.27 mmol) in acetonitrile (60 mL) at RT was added drop-wise a solution of DCC (4.28 g, 20.76 mmol) in acetonitrile (20 mL). The reaction mixture was stirred for 2h before being filtered. The filtrate was concentrated under reduced pressure and extracted with EtOAc/ water then washed successively with sat. NaHC03 and brine. The organic layer was dried over Na2S04 and evaporated. The crude solid was dissolved in DCM and precipitated with cyclohexane, filtered and dried to give the desired product ethyl 3-([4-(methyloxy)phenyl]acetyl}amino)-1 H-pyrrole-2- carboxylate (1.5 g, 4.96 mmol, 38.2 % yield) as a cream powder. LCMS: (M+H)+ : 303; Rt: 2.83 min.
16A) 1-(2-Chloro-4-fluorophenyl)-2-(4-methoxyphenyl)ethanone 230 ml of a 2M solution of NaHMDS in THF are introduced into 250 ml of THF under nitrogen. The solution is cooled to -60 C. and then 30.5 g of (4-methoxyphenyl)acetic acid in 120 ml of THF are added at this temperature. After 1 h 30 min at -60 C., 33 g of <strong>[85953-29-3]methyl 2-chloro-4-fluorobenzoate</strong> are added and the mixture is stirred at -60 C. for 45 min and then allowed to return to 0 C. The reaction medium is poured onto 500 ml of ice-cold 2N HCl and extracted with ether and the extract is washed with water and then with a saturated aqueous sodium chloride solution. After drying, concentrating to dryness and then crystallizing from pentane, 27.4 g of the expected compound are obtained.
With potassium carbonate; In acetonitrile; at 80℃;
General procedure: To the flame dried K2CO3 (14.5 g, 0.104 mol), were added 2-chloro-1-(2,4-difluorophenyl)ethanone (5.0 g, 0.026 mol) and 3,4-dichloro phenyl acetic acid (5.38 g, 0.026 mol) in acetonitrile (100 ml) at room temperature and the reaction mixture was refluxed for 4 h. It was then cooled to room temperature, diluted with water, extracted with ethyl acetate, dried over Na2SO4, concentrated and purified by column chromatography using pet ether-ethyl acetate (90:10) as eluent to give pure compound 3-(3,4-dichlorophenyl)-4-(2,4-difluorophenyl) furan-2(5H)-one (18b); Yield: 81%; Nature: Yellow solid; M. p. 127 0C; IR (Chloroform): nu max 1145, 1164, 1272, 1361, 1429, 1472, 1593, 1611, 1648, 1754, 2934, 3021, 3082, 3105 cm-1. 1H NMR (200 MHz, CDCl3): delta 5.18 (s, 2H), 6.84-6.98 (m, 2H), 7.15-7.26 (m, 2H), 7.41 (d, J=8 Hz, 1H), 7.55 (d, J=2 Hz, 1H). 13C NMR (200 MHz, CDCl3): delta 71.0 (d), 105.2 (t), 112.5 (d), 114.5(d), 125.7, 128.0, 129.5, 130.5 (2C), 130.9 (d), 132.7, 133.1, 152.3, 159.5 (dd), 164.6 (dd), 171.6. MS (ESI) m/z: 362.94 (M + Na).
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;
General procedure: To a round-bottom flask (500 mL) that contained a solution of aryl sulfonamide (6 mmol), 4-dimethyaminopyridine (DMAP, 13 mmol), and 1-[3-(dimethyamino)-propyl]-3-ethylcarbodiimide hydrochloride (EDCI, 13 mmol) in CH2Cl2 (150 mL) was added the synthesized phenylacetic acid (6 mmol) at room temperature. The resulting mixture was stirred at room temperature for 12 h, then cooled to 5 C, and acidified to pH 1 with addition of HCl aqueous solution (10%), which was followed by extraction with CH2Cl2/MeOH (9:1, 3 × 100 mL). The combined organic layers were washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The residue was subjected to silica gel chromatography or crystallization if necessary to afford the compounds (20-44) (Scheme 2).
With sodium sulfate; In methanol; at 50℃; for 24h;
General procedure: To a solution of substituted indole-3-carbaldehyde 1 (1.5 mmol) in methanol (5 mL) were addedsuccessively Na2SO4 (0.3 g), propargylamine 2 (1.1 equiv), acid 3 (1.1 equiv) and isonitrile 4(1.1 equiv) in a 25 mL RBF equipped with a magnetic stir bar. The reaction mixture was stirredat 50 C for 24 h. After completion of the reaction, the mixture was diluted with EtOAc (100 mL) and was extracted with water (50 mL). The organic layer was washed with brine(50 mL), dried over magnesium sulfate and evaporated under reduced pressure to obtain residuewhich was subjected to silica gel column chromatography (80% EtOAc in heptane) to afford thedesired product 5a-q as solid.
2-(4-methoxyphenyl)-3-(4-((E)-3-methoxy-3-oxoprop-1-en-1-yl)phenyl)acrylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; In acetic anhydride; at 30℃; for 2h;
General procedure: General procedure A Step-a: Synthesis of 2-(4-fluorophenyl)-3-(4-((E)-3-methoxy-3-oxoprop-1-en-1-yl) phenyl) acrylic acid (C). A mixture of 4-fluorophenylacetic acid (2.5 g, 13.2 mmol) and methyl (E)-3-(4-formylphenyl)acrylate (2.03 g, 13.2 mmol) were dissolved under stirring with acetic anhydride (8 ml). To this mixture diisopropylethylamine (DIPEA) (3.4 ml, 19.7 mmol) was added and stirred at 30 C for 2 h. Upon completion (as monitored by TLC using 100% ethyl acetate as eluent), the reaction mixture was poured into water and the pH was adjusted to 1 using dil. HClaq (1:1). The aqueous layer was extracted with ethyl acetate (2 * 150 ml). The combined ethyl acetate layer was washed with water till the washings were neutral and dried over anhydrous Na2SO4. The ethyl acetate layer was evaporated to dryness to obtain a sticky compound, which was triturated with cold dichloromethane (DCM) to furnish a white solid. It was filtered and dried under vacuum to afford the title compound (2 g, 47%).
N,4-Dimethoxy-N-methylbenzamide (12s, Q= OCH3). To a suspension of 4- methoxyphenylacetic acid (1.02 g, 6.6 mmol) in DCM (21 ml) oxalyl chloride (1,2 ml, 13.8 mmol, 2.1 eq.) was added at 0C. After 3.5 h at 0C a slightly yellow solution was formed. The solution was added dropwise during 1 h to a suspension of N,O-dimethylhydroxylamine hydrochloride (1.09 g, 11 mmol) and triethylamine (9.6 ml, 6.91 g, 68 mmol, 10 eq.) in DCM(17 ml) at 0C. After 4 h when the temperature had reached it water (25 ml) was added to the reaction mixture. The organic phase was separated, washed with aq. sat. NaHCO3 (2x25 ml), aq. sat. NaC1 (20 ml), dried over Na2SO4 and concentrated at reduced pressure to afford a slightly yellow oil (0.83 g, 64%). The crude product was purified by silica gel flash chromatography (hept/EtOAc 3:1 to 0:1) to afford a colourless oil 12s (0.71 g, 55%).
With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 23℃;Inert atmosphere;
General procedure: To a flame-dried round-bottom flask with a magnetic stir bar were added the aryl acetic acid (12.0 mmol, 1.00 equiv) and dry dichloromethane (13 mL). The solution was stirred under nitrogen while DMAP (approx. 50 mg) and the alcohol (12.0 mmol, 1.00 equiv) were added. The solution was cooled to 0 C using an ice water bath and DCC (2.72 g, 13.2 mmol, 1.10 equiv) was added. The mixture was allowed to stir for five minutes at 0 C, and then the ice water bath was removed and the mixture was allowed to warm to 23C. Upon completion (as determined by TLC analysis), the heterogeneous mixture was filtered through Celite, rinsing with dichloromethane (20 mL). The filtrate was concentrated, suspended in dichloromethane, and filtered through Celite, washing with dichloromethane (20 mL). The filtrate was washed with 0.5 M aqueous hydrochloric acid (2 x 50 mL) and saturated aqueous sodium bicarbonate (1 x 50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography using a mixture of hexanes and ethyl acetate as eluent. To a flame-dried round-bottom flask with a magnetic stir bar were added the aryl acetic acid ester (10.0 mmol, 1.00 equiv), p-ABSA (2.88 g, 12.0 mmol, 1.20 equiv), and dry acetonitrile (35 mL). The solution was stirred under nitrogen and cooled to 0 C using an ice water bath. DBU (1.65 mL, 11.0 mmol, 1.10 equiv) was added by syringe rapidly in one portion, and the reaction mixture was allowed to warm to 23 C and stir overnight. Upon completion (as determined by TLC analysis) or after 24 hours, whichever came first, the reaction mixture was quenched with saturated aqueous ammonium chloride (50 mL) and extracted with ether (3 x 50 mL). The combined organic layers were washed with brine (1 x 100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography using a mixture of hexanes and ethyl acetate as eluent. The aryl diazoacetates were obtained in 12-50% yield over two steps.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Inert atmosphere;
General procedure: An oven-dried 50 mL round-bottom flask containing a magnetic stirrer bar was sealed with a septum, charged with Ar and tared on a balance. KH (~0.5 g, 30% mineral oil dispersion) was then added to the flask and the mineral oil removed by trituration under Ar with pet. spirit (2 x 30 mL) using a syringe. The flask containing dry KH was purged with Ar and reweighed to obtain an accurate mass of KH. Dry THF (10 mL) was added to the flask containing KH (0.15 g, 3.7 mmol, under Ar) and the mixture cooled to 0 oC. 3,5-Dimethyl-1H-pyrrole-2-carbaldehyde 5 (0.23 g, 1.9 mmol) was dissolved in dry THF (5 mL) under Ar and added dropwise to the stirring KH solution (Caution - flask requires outlet needle to release evolving H2 gas). After complete addition the mixture was stirred for a further 5 minutes at 0 oC. The phenylacetic acid derivative (1.9 mmoles) was added to a separate dry 50 mL round-bottom flask under Ar along with HBTU (0.71 g, 1.9 mmoles) and dry CH2Cl2 (10 mL). DIPEA (0.65 mL, 3.7 mmoles) was added dropwise to the stirring solution and upon complete addition the mixture was stirred for a further 5 minutes or until the HBTU was completely dissolved. The HBTU solution was then cooled to 0 oC and added in a single portion to the K+ pyrrolate salt solution at 0 oC and the combined mixture allowed to warm slowly to room temperature. A dark red colour observed in each reaction indicated formation of the desired 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-one. The reaction was quenched after ~ 2 h with ice-cold water (100 mL) and extracted with Et2O (2 x 50 mL). The combined organic phase was washed with 1 M HCl (2 x 50 mL), saturated NaHCO3 (2 x 50 mL) and brine (2 x 50 mL), dried over anhydrous MgSO4 and concentrated. The crude residue was purified by silica gel column chromatography using a gradient from 100% pet. spirit to 1:9 acetone:pet. spirit to afford the 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-one as a deep red solid.
General procedure: An equimolar mixture of aralkanoic acid hydrazides 3 andsubstituted aromatic acids were mixed in phosphorous oxychlorideand heated under reflux at 107 C for 3 h. The reaction progresswasmonitored by thin layer chromatography. After consumption of thestarting material; the reaction mixture was cooled to room temperatureand poured into crushed ice which becomes precipitated.These precipitates was filtered, washed with cold water and diethylether, filtered and crystallized on methanol to get 2,5-disubstituted-1,3,4-oxadiazoles 4a-k. The product was purifiedwith column chromatography. 2.3.2. 2,5-Bis(4-methoxybenzyl)-1,3,4-oxadiazole (4a)Off white solid; yield: 71%; Rf: 0.64 (n-hexane: ethyl acetate,8:2); FTeIR (n/cm1): 3026 (sp2 CH), 2945 (sp3 CH), 1579 (CN),1551, 1498 (CC of phenyl ring); 1H NMR (400 M Hz, DMSO-d6)d 7.19e7.00 (m, 4H, aromatic proton), 6.98e6.89 (m, 2H, aromaticproton), 6.88e6.68 (m, 2H, aromatic proton), 3.66 (s, 2H, aliphaticCH2), 3.64 (s, 3H, methoxy proton), 3.60 (s, 2H, aliphatic CH2); 13CNMR (100 MHz, DMSO-d6) d 158.4, 155.1, 149.3, 147.0, 130.0, 127.6,125.8, 120.5, 114.1, 120.0, 56.1, 55.9, 31.5.
71%
With trichlorophosphate; at 107℃; for 3h;
The equimolar mixture of aralkanoic hydrazide (3) and substituted aromatic acids was mixed with phosphorus oxychloride and heated at reflux at 107 C. for 3 hours. The reaction process was monitored by thin layer chromatography, after which the starting material was consumed, the reaction mixture was cooled to room temperature and poured on ice to precipitate. These precipitates were filtered, washed with cold water and diethyl ether, filtered and crystallized with methanol,As a final product the 2 and 5-position substituted in 1,3,4-oxadiazole compound 4a to 4k was obtained.The product obtained was purified by column chromatography
2-(4-methoxybenzyl)-1H-benzo[d]imidazol-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; In water; for 16h;Reflux;
General procedure: To a solution of the corresponding substituted alkyloxybenzene-1,2-diamine 4 (2.26 mmol) in 6N HCl (10 mL), corresponding acid 5 (6.80 mmol) was added. The resulting solution was refluxed for 16 h. The reaction mixture was cooled to 0 °C, diluted with EtOAc, and then pH was adjusted to ~ 7 by using solid NaHCO3, extracted with EtOAc. The combined organic extracts were washed with brine solution, dried over anhydrous Na2SO4 and then concentrated under reduced pressure. The crude mixture was subjected to flash silica gel (230?400 mesh) column chromatography to afford the title compounds 6a?f and 6h?s.
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