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Structure of 23680-40-2 * Storage: {[proInfo.prStorage]}
* 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.
With N-Bromosuccinimide; silver nitrate In acetone at 20 - 32℃;
To methyl propiolate (60 g, 713.6 mmol) dissolved in acetone (2 L) was added N- bromosuccinimide (147.22 g, 827.13 mmol), followed by silver nitrate (12.12 g, 71 .37 mmol). A slight exotherm was observed with the reaction temperature increasing from 21 - 32 °C before the reaction mixture was left to stir at room temperature overnight. The resulting grey suspension was evaporated to dryness in vacuo, pentane added (100 ml_) and filtered through Celite®, washing through with more pentane. This procedure was carried out twice more and then the combined filtrates evaporated in vacuo to give 1 13 g of methyl 3-bromopropiolate (98percent yield) containing approximately 10percent of starting material.1H NMR (400 MHz, CDCI3) δ ppm 3.78 (s, 3 H).
88%
With N-Bromosuccinimide; silver nitrate In acetone at 20℃; for 6 h;
[1067] Methyl propiolate (52 ml, 0.583 mole) is combined with recrystallized N-bromo-succinimide (120 g, 0.674 mole) in 1,700 ml acetone under nitrogen. The solution is treated with silver nitrate (9.9 g, 0.0583 mole) neat in a single lot and the reaction is stirred 6 h at RT. The acetone is removed under reduced pressure (25° C., bath temperature) to provide a gray slurry. The slurry is washed with 2.x.200 ml hexane, the gray solid is removed by filtration, and the filtrate is concentrated in vacuo to provide 95 g of a pale yellow oily residue. The crude material was distilled via short path under reduced pressure (65° C., about 25 mm Hg) into a dry ice/acetone cooled receiver to give 83.7 g (88percent) of methyl-3-bromo-propiolate as a pale yellow oil. Anal. calc'd for C4H3BrO2: C, 29.48; H, 1.86. Found: C, 29.09; H, 1.97.
88%
With N-Bromosuccinimide; silver nitrate In acetone at 20℃; for 6 h;
Methyl propiolate (52 ml, 0.583 mole) is combined with recrystallized N-bromo-succinimide (120 g, 0.674 mole) in 1,700 ml acetone under nitrogen. The solution is treated with silver nitrate (9.9 g, 0.0583 mole) neat in a single lot and the reaction is stirred 6 h at RT. The acetone is removed under reduced pressure (25° C., bath temperature) to provide a gray slurry. The slurry is washed with 2.x.200 ml hexane, the gray solid is removed by filtration, and the filtrate is concentrated in vacuo to provide 95 g of a pale yellow oily residue. The crude material was distilled via short path under reduced pressure (65° C., about 25 mm Hg) into a dry ice/acetone cooled receiver to give 83.7 g (88percent) of methyl-3-bromo-propiolate as a pale yellow oil. Anal. calc'd for C4H3BrO2: C, 29.48; H, 1.86. Found: C, 29.09; H, 1.97.
88%
With N-Bromosuccinimide In acetone at 20℃; for 6 h;
Methyl propiolate (52 ml, 0.583 mol) is combined with recrystallized N- BROMO-SUCCINIMIDE (120 g, 0.674 mol) in 1,700 ml acetone under nitrogen. The solution is treated with silver nitrate (9.9 g, 0.0583 mol) neat in a single lot and the reaction is stirred 6 h at RT. The acetone is removed under reduced pressure (25°C, bath temperature) to provide a gray slurry. The slurry is washed with 2 x 200 ML hexane, the gray solid is removed by filtration, and the filtrate is concentrated in vacuo to provide 95 g of a pale yellow oily residue. The crude material is distilled via short path under reduced pressure (65°C, about 25 mm Hg) into a dry ice/acetone cooled receiver to give 83.7 g (88percent) of methyl-3-bromo-propiolate as a pale yellow oil. Anal. calc'd for C4H3BR02 : C, 29.48 ; H, 1.86. Found: C, 29.09 ; H, 1.97
88%
With N-Bromosuccinimide; silver nitrate In acetone at 20℃; for 6 h; Inert atmosphere
An alternate procedure for the bromination using methyl propiolate is described in a 2003 US patent publication US2003/236270 A1. Methyl propiolate (52 ml, 0.583 mol) is combined with recrystallized N-bromo-succinimide (120 g, 0.674 mol) in 1,700 ml acetone under nitrogen. The solution is treated with silver nitrate (9.9 g, 0.0583 mol) neat in a single lot and the reaction is stirred 6 h at RT. The acetone is removed under reduced pressure (25° C., bath temperature) to provide a gray slurry. The slurry is washed with 2×200 ml hexane, the gray solid is removed by filtration, and the filtrate is concentrated in vacuo to provide 95 g of a pale yellow oily residue. The crude material was distilled via short path under reduced pressure (65° C., about 25 mm Hg) into a dry ice/acetone cooled receiver to give 83.7 g (88percent) of methyl-3-bromo-propiolate as a pale yellow oil
83%
With N-Bromosuccinimide; silver nitrate In acetone at 0 - 20℃; for 4.5 h; Inert atmosphere
To a stirred solution of methyl propiolate (50 g, 594 mmol, Spectrochem) in dry acetone(300 mL), silver nitrate (1.01 g, 5.94 mmol, Spectrochem) was added and cooled to 0 00 under N2 atmosphere. N-bromo succinimide (116 g, 654 mmol, Spectrochem) was added in portions over 30 mm and allowed to warm to room temperature. Reaction mixture was allowed to stir at RT for 4 h. The reaction mixture was concentrated and taken up in hexane and filtered through celite bed. The filtrate was concentrated in Rota-evaporator and residue obtained was purified by distillation to get the titled compound as colorless liquid (81 g, 83percent). 1H NMR (400 MHz, CDCI3): 6 3.78 (s, 3H).
83%
With N-Bromosuccinimide; silver nitrate In acetone at 0 - 20℃; Inert atmosphere
Step 1: Bromo-propynoic acid methyl ester To a stirred solution of methyl propiolate (50 g, 594 mmol, Spectrochem) in dry acetone (300 mL), silver nitrate (1.01 g, 5.94 mmol, Spectrochem) was added and cooled to 0 °C under N2 atmosphere. N-bromo succinimide (116 g, 654 mmol, Spectrochem) was added in portions over 30 min and allowed to warm to room temperature. Reaction mixture was allowed to stir at RT for 4 h. The reaction mixture was concentrated and taken up in hexane and filtered through celite bed. The filtrate was concentrated in Rota-evaporator and residue obtained was purified by distillation to get the titled compound as colorless liquid (81 g, 83percent). 1H NMR (400 MHz, CDCl3): δ 3.78 (s, 3H).
72.3%
Stage #1: With silver nitrate In acetone at 20℃; for 0.166667 h; Inert atmosphere Stage #2: With N-Bromosuccinimide In acetone at 20℃; for 2 h;
To a solution of S1 (100.0 g, 1.19 mol) in acetone (1.5 L) was added AgNO3 (202.2 g, 1.19 mol) at room temperature. After stirring for 10 min, NBS (243.6 g, 1.37 mol) was added. Then the reaction mixture was stirred at room temperature for additional 2 hrs. The reaction mixture was filtered and the filtrate was evaporated in vacuo to afford crude product, which was further purified by distilled (10 mmHg, 85~90 oC) to afford S2 as yellow oil (210.0 g, yield: 72.3percent). 1H NMR (400MHz, CHLOROFORM-d): δ 3.80 (s, 3H).
49%
With N-Bromosuccinimide; silver nitrate In [(2)H6]acetone at 20℃; for 20 h;
Into a 250-mL round-bottom flask, was placed a solution of methyl prop-2-ynoate (1) (4.9 g, 58.28 mmol, 1.00 equiv) in acetone (dried over magnesium sulfate) (120 mL). NBS (15 g, 84.28 mmol, 1.40 equiv) and AgNO3 (1.0 g, 0.10 equiv) were added to the reaction. The resulting solution was stirred for 20 h at room temperature. The solids were filtered out. The resulting mixture was concentrated under vacuum. The crude product was purified by distillation and the fraction was collected at 40-55° C. This provided 4.7 g (49percent) of methyl 3-bromoprop-2-ynoate (2) as a colorless oil.
Reference：
[1] Patent: WO2015/166373, 2015, A1, . Location in patent: Page/Page column 148
[2] Organic Syntheses, 1997, vol. 74, p. 212 - 212
[3] Synthetic Communications, 1992, vol. 22, # 4, p. 567 - 572
[4] Patent: US2003/236264, 2003, A1, . Location in patent: Page 44
[5] Patent: US2003/236270, 2003, A1, . Location in patent: Page 33
[6] Patent: WO2004/52889, 2004, A1, . Location in patent: Page 52-53
[7] Patent: US2015/329554, 2015, A1, . Location in patent: Paragraph 0372
[8] Patent: WO2014/198808, 2014, A1, . Location in patent: Page/Page column 100
[9] Patent: EP2813505, 2014, A1, . Location in patent: Paragraph 0105
[10] European Journal of Organic Chemistry, 2017, vol. 2017, # 1, p. 138 - 148
[11] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 22, p. 4979 - 4984
[12] Chemistry--A European Journal, 2014, vol. 20, # 35, p. 11101 - 11110,10
[13] Patent: US2015/141465, 2015, A1, . Location in patent: Paragraph 0342
[14] Annales de Chimie (Cachan, France), 1957, vol. <13> 2, p. 819,861, 862
[15] Tetrahedron, 2006, vol. 62, # 50, p. 11635 - 11644
[16] Tetrahedron, 2007, vol. 63, # 13, p. 2888 - 2900
[17] Journal of the American Chemical Society, 2007, vol. 129, # 2, p. 441 - 449
[18] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 15, p. 5262 - 5274
[19] Patent: WO2009/55331, 2009, A2, . Location in patent: Page/Page column 201
[20] Organic Letters, 2014, vol. 16, # 11, p. 3024 - 3027
[21] Tetrahedron Letters, 2014, vol. 55, # 38, p. 5302 - 5305
[22] Advanced Synthesis and Catalysis, 2015, vol. 357, # 4, p. 719 - 726
[23] Patent: WO2018/118838, 2018, A1, . Location in patent: Paragraph 001667; 001668
2
[ 128-08-5 ]
[ 922-67-8 ]
[ 23680-40-2 ]
Yield
Reaction Conditions
Operation in experiment
88%
With silver nitrate In acetone at 20℃; for 6 h;
Methyl propiolate (52 ml, 0.583 mol) is combined with recrystallized N- bromo-succinimide (120 g, 0.674 mol) in 1,700 ml acetone under nitrogen. The solution is treated with silver nitrate (9.9 g, 0.0583 mol) neat in a single lot and the reaction is stirred 6 h at RT. The acetone is removed under reduced pressure (25C, bath temperature) to provide a gray slurry. The slurry is washed with 2 x 200 ml hexane, the gray solid is removed by filtration, and the filtrate is concentrated in vacuo to provide 95 g of a pale yellow oily residue. The crude material is distilled via short path under reduced pressure (65C, about 25 mm Hg) into a dry ICE/ACETONE cooled receiver to give 83.7 g (88percent) of methyl-3-bromo-propiolate as a pale yellow oil. Anal. calc'd for C4H3BRO2 : C, 29.48 ; H, 1.86. Found: C, 29.09 ; H, 1.97.
A solution of <strong>[23680-40-2]methyl 3-bromopropiolate</strong> (1 b, 200 g, 1 .23 mol), furan (419 g, 6.15 mol, 445 mL) in toluene (2.50 L) was degassed by passing nitrogen gas through the reaction vessel for 2 min at 0 C, then the reaction mixture was warmed to 90 C for 72 hour to give a black solution. The reaction mixture was concentrated, and the residue was purified by column chromatography (2-5% EtOAc/PE) to give methyl 3-bromo-7-oxabicyclo[2.2.1 ]hepta-2,5-diene- 2-carboxylate. Four batches were purified separately and combined to afford methyl 3-bromo-7- oxabicyclo[2.2.1 ]hepta-2,5-diene-2-carboxylate (1 c) as a yellow oil.1H NMR (400 MHz, CDCI3) delta = 7.25 - 7.17 (m, 2H), 5.70 (t, J = 1 .6 Hz, 1 H), 5.33 (t, J = 1 .7 Hz, 1 H), 3.82 - 3.75 (m, 3H).
methyl 3-bromobicyclo[2.2.1]hepta-2,5-diene-2-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
In toluene; at 90℃; for 2h;Inert atmosphere;
Methyl 3-bromopropiolate (1 13 g, 698 mmol) and freshly cracked cyclopentadiene (92 g, 1 .39 mol) were dissolved in toluene (570 ml_) and heated to 90 C, under nitrogen for 2 hr. The reaction was cooled to room temperature, and the toluene evaporated in vacuo to give a dark brown oil. This was azeotroped three times with acetonitrile to remove excess dicyclopentadiene, giving the title compound (1 19 g, 74% yield) as a brown oil. 1 H NMR (400 MHz, CDCI3) delta ppm 6.88 - 6.94 (m, 1 H), 6.85 (ddd, J = 5.2, 3.1 , 1 .0 Hz, 1 H), 4.00 (dqd, J = 2.8, 1 .7, 0.8 Hz, 1 H), 3.76 (s, 3 H), 3.69 (ddtd, J = 3.2, 2.4, 1 .5, 0.7 Hz, 1 H), 2.32 (dt, J = 6.7, 1 .7 Hz, 1 H), 2.13 (dt, J = 6.7, 1 .7 Hz, 1 H).
Methyl-3-bromo-propiolate (83.7 g, 0.513 mol) is added to N-T-BUTYLOXY- pyrrole (430 ml, 2.57 mol) under nitrogen. The dark mixture is warmed in a 90 C bath for 30 h, is cooled, and the bulk of the excess N-T-BUTYLOXY-PYRROLE is removed in vacuo using a dry ice/acetone condenser. The dark oily residue is chromatographed over 1 kg silica gel (230-400 mesh) eluting with 0-15% EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 97 g (57%) of 7-tert- butyl 2-methyl 3-bromo-7-azabicyclo [2.2. 1] hepta-2,5-diene-2, 7-dicarboxylate as a dark yellow oil. HRMS (FAB) calc'd for C13HL6BRNO4+H : 330.0341, found 330.0335 (M+H) +.
57%
at 90℃; for 30h;
METHYL-3-BROMO-PROPIOLATE (83.7 g, 0.513 mol) is added to N-T-BUTYLOXY- pyrrole (430 ml, 2.57 mol) under nitrogen. The dark mixture is warmed in a 90 C bath for 30 h, is cooled, and the bulk of the excess N-T-BUTYLOXY-PYRROLE is removed in vacuo using a dry ICE/ACETONE condenser. The dark oily residue is chromatographed over 1 kg silica gel (230-400 mesh) eluting with 0-15% EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 97 g (57%) of 7-tert- butyl 2-methyl 3-bromo-7-azabicyclo [2.2. 1] hepta-2,5-diene-2, 7-dicarboxylate as a dark yellow oil. HRMS (FAB) calc'd for CL3HL6BRNO4+H : 330.0341, found 330.0335 (M+H) + Preparation of (+/-) E77DO-7-TERT-BUTYL 2-methyl 7-azabicyclo [2.2. 1] heptane- 2,7-dicarboxylate.
Methyl propiolate (52 ml, 0.583 mol) is combined with recrystallized N- bromo-succinimide (120 g, 0.674 mol) in 1,700 ml acetone under nitrogen. The solution is treated with silver nitrate (9.9 g, 0.0583 mol) neat in a single lot and the reaction is stirred 6 h at RT. The acetone is removed under reduced pressure (25C, bath temperature) to provide a gray slurry. The slurry is washed with 2 x 200 ml hexane, the gray solid is removed by filtration, and the filtrate is concentrated in vacuo to provide 95 g of a pale yellow oily residue. The crude material is distilled via short path under reduced pressure (65C, about 25 mm Hg) into a dry ICE/ACETONE cooled receiver to give 83.7 g (88%) of methyl-3-bromo-propiolate as a pale yellow oil. Anal. calc'd for C4H3BRO2 : C, 29.48 ; H, 1.86. Found: C, 29.09 ; H, 1.97.
6-ethynylsulphonyl-1,1,4,4,7-pentamethyl-1,2,3,4-tetrahydronaphthalene[ No CAS ]
[ 23680-40-2 ]
ammonium chloride[ No CAS ]
[ 75-04-7 ]
methyl 5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylsulphonyl)penta-2,4-diynoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydroxylamine hydrochloride; In methanol; water; ethyl acetate;
EXAMPLE 35 Methyl 5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylsulphonyl)penta-2,4-diynoate A 70% solution of ethylamine in water (563 mul) is added dropwise to a mixture of methyl 3-bromopropynoate (632 mg, 2.88 mmol), hydroxylamine hydrochloride (162 mg, 2.33 mmol) and copper (I) chloride (10 mg) in methanol. A solution of 6-ethynylsulphonyl-1,1,4,4,7-pentamethyl-1,2,3,4-tetrahydronaphthalene (Example 7(b)) (500 mg, 1.94 mmol) in methanol (5 ml) is then added dropwise. The reaction medium is stirred for 15 h at room temperature and treated with saturated aqueous ammonium chloride solution and ethyl acetate. The organic phase is washed with water, dried over magnesium sulphate and concentrated. The product is obtained in the form of an oil after purification by flash chromatography on silica (80/20 heptane/CH2Cl2). 1H NMR/CDCl3: 1.26 to 1.28 (s, 12H); 1.67 (s, 4H); 2.35 (s, 3H); 3.78 (s, 3H); 7.14 (s, 1H); 7.48 (s, 1H); 13C NMR/CDCl3: 19.7; CH3/31.8; 4*CH3/34.1; Cq/34.3; Cq/34.9; 2*CH2/52.9; CH3/71.7; CH/72.1; CH/80.2; Cq/124.5; Cq/127.6; Cq/12.8.3; CH/129.3; CH/134.8; Cq/144.6; Cq/146.2; Cq/153.4; Cq.
d Methyl 5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylselenyl)penta-2,4-diynoate In a manner similar to that of Example 35, the expected product is obtained by coupling 321 mg of methyl bromopropynoate and 200 mg of 6-ethynylselenyl-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene, in a yield of 28% (70 mg). 1H NMR/CDCl3: 1.23 (s, 6H); 1.33 (s, 6H); 1.67 (s, 4H); 2.35 (s, 3H); 3.79 (s, 3H); 7.13 (s, 1H); 7.65 (s, 1H).
EXAMPLE 5 Methyl 3-Bromo-3-Thiocyanoacrylate (Compound 22) To a stirred solution of ammonium thiocyanate (3.06 g., 0.04 mole) in 2M aqueous sulfuric acid (20 ml) at 0 C., <strong>[23680-40-2]methyl 3-bromopropiolate</strong> (3.26 g., 0.02 mole) was added dropwise, neat, over 5 minutes. After keeping the temperature at 0 C. for 1 hour, the mixture, consisting of a solid precipitate in the aqueous solution, was extracted with ether which was washed with water, dried (MgSO4), and concentrated. The residual solid was suspended in hexane and removed by filtration, yielding 2.4 g. of product. The solid recrystallized from ethanol as yellowish microcrystals; mp 139-142.5 C.; IR (KBr) 2170, 1680 cm-1.
(1SR,4RS)-7-tert-butyl 2-methyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
30%
at 90℃; for 20h;
Into a 50-mL round-bottom flask, was placed tert-butyl 1H-pyrrole-1-carboxylate (3) (14.4 g, 86.12 mmol, 3.00 equiv), <strong>[23680-40-2]methyl 3-bromoprop-2-ynoate</strong> (2) (4.7 g, 28.84 mmol, 1.00 equiv). The resulting solution was stirred for 20 h at 90 C. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:30?1:15) as eluent to furnish 2.89 g (30%) of 7-tert-butyl 2-methyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate (4) as a yellow oil.
1-amino-4-(diisopentylcarbamoyl)pyridin-1-ium 2,4-(dinitro)phenolate[ No CAS ]
[ 1391990-13-8 ]
Yield
Reaction Conditions
Operation in experiment
5.47%
With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 22℃; for 18h;
Intermediate 142Cmethyl 2-bromo-5-(diisopentylcarbamoyl)pyrazolo[1 ,5-a]pyridine-3-carboxylateA suspension of /V-aminopyridinium 2,4-(dinitro)phenolate (10 g, 21.67 mmol), methyl 3- bromopropiolate (3.12 ml, 26.0 mmol) and potassium carbonate (5.99 g, 43.3 mmol) in degassed DMF (75 ml) was stirred at 0 C for 5 minutes and at 22 C for 18h. The mixture was diluted with ethyl acetate (100 mL) and washed with water (3 x 25 mL), brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (120g, 0% to 100% ethyl acetate/hexanes over 19 min). to provide methyl 2-bromo-5-(diisopentylcarbamoyl)pyrazolo[1 ,5- a]pyridine-3-carboxylate (0.52 g, 1.186 mmol, 5.47 % yield). LCMS m/z 438.4, 440.1 (M + H)+.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
(1SR,4RS)-3-bromo-1-pentyl-7-oxabicyclo[2.2.1]hepta-2,5-diene-2-carboxylic acid methyl ester[ No CAS ]
C13H17BrO3[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In toluene; for 24h;Reflux; Inert atmosphere;
Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
methyl 2-bromo-3-hydroxy-6-pentylbenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to a two-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion of the initial Diels-Alder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture was stirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
methyl 2-bromo-3-hydroxy-6-pentylbenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
6%Spectr.; 82%
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
methyl 2-bromo-3-hydroxy-6-(4'-trifluoromethylphenyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%Spectr.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
methyl 2-bromo-6-(4'-cyanophenyl)-3-hydroxybenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
40%Spectr.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added to atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, silica gel (150 mg) was added under flow of nitrogen and the mixture wasstirred at reflux for 2 h. After removal of the solvent and filtration, a product 4 was purified by silica gelcolumn chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
methyl 2-bromo-5,6-dimethyl-3-hydroxybenzoate[ No CAS ]
C10H11BrO3[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%Spectr.; 11%Spectr.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
General procedure: Methyl 3-bromopropiolate 2 (0.5 mmol), furan 1 (0.6 mmol) and distilled toluene (1.5 mL) were added in atwo-necked flask, and the mixture was stirred at reflux for 24 h under nitrogen atmosphere. After completion ofthe initial DielsAlder reaction, FeCl3 (10 mol%) was added under flow of nitrogen and the reaction mixture was stirred at reflux for 2 h. After removal of the solvent and filtration through a pad of silica, a product 4 was purified by silica gel column chromatography or PTLC using a mixture of ethyl acetate and n-hexane as an eluent.
3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylic acid 7-tert-butyl ester 2-methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
at 95℃; for 48h;
A mixture of <strong>[23680-40-2]bromo-propynoic acid methyl ester</strong> (81.2 g, 497 mmol) and t-butyl pyrrole-1-carboxylate (216.7 g, 1292 mmol, Combiblock) were combined and heated to 95Cfor2days. After completion of the reaction, the reaction mixture was concentrated in high vacuum and purified by flash column chromatography (230-400 size mesh silica gel)using gradient elution of ethyl acetate (7.5-8.0%) in n-hexane to afford the pure product as reddish brown gel. 1H NMR (400 MHz, DMSO-d6): 6 7.25-7.22 (m, 2H), 5.30 (s, 1 H),5.15 (s, 1H), 3.72 (s, 3H), 1.34 (s, 9H). LCMS: (Method A) 232.0 (M-Boc-f-H), Rt. 4.7 mm, 95.6% (Max).
A mixture of compound S4a (10 g, 56.5 mmol) and tert-butyl 1H-pyrrole-1-carboxylate (50 mE) was stirred at 1100 C. for 12 hours. The reaction mixture was cooled down to room temperature and purified by column chromatography (EtOAc/PE) to give compound 84b (7 g, yield, 37% yield). ?H NMR (400 MHz, CDC13) 7.13 (brs, 2H), 5.48 (brs, 1H), 5.13 (brs, 1H), 4.15-4.37 (m, 2H), 1.41 (s, 9H), 1.32 (t, J=7.15, 3H).
20%
at 90℃; for 14h;Sealed tube;
Reaction Step 2. Synthesis of 7-tert-butyl 2-ethyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylateA mixture of <strong>[23680-40-2]methyl 3-bromopropiolate</strong> (5.00 g, 28.2 mmol, 1.0 eq) and tert-butyl 1H-pyrrole-1-carboxylate (14.00 g, 84.7 mmol, 3.0 eq) in a sealed tube was heated to 90 C. for 14 h. After completion of the reaction (monitored by TLC, 5% ethyl acetate-hexane Rf=0.3), The reaction mixture was purified without work up by flash column chromatography on silica gel (100-200 mesh), eluting with 5% ethyl acetate in hexanes to afford 7-tert-butyl 2-methyl 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate (2.0 g, 20%) as a brown oil. LCMS m/z=344.2 (M+1); purity=75%.
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