Stage #1: With hydrogen bromide In acetic acid at 75℃; for 4 h; Stage #2: at 20℃;
A solution of γ-butyrolactone (25 mL, 28.0 g, 0.325 mole) in a 45percent solution of hydrogen bromide in acetic acid (75 mL) was heated for 4 h at 75° C., cooled to room temperature, treated with methanol (150 mL), and stirred overnight. Evaporation of the solvent gave a dark oil, which was dissolved in ethyl acetate (150 mL) and washed successively with saturated sodium bicarbonate (2.x.150 mL), saturated sodium chloride (150 mL), dried over anhydrous magnesium sulfate, and evaporated to yield a clear oil (48.8 g, 86percent). 1Hmr (CDCl3, δ): 3.68 (3H, s, OCH3), 3.44 (2H, t, 6.4 Hz, CH2γ), 2.51 (2H, t, 7.2 Hz, CH2α), 2.17 (2H, quintet, 6.8 Hz, CH2β). 13Cmr (CDCl3, δ): 172.96, 51.70, 32.66, 32.19, 27.70. IR (neat): 1738 cm-1. Mass spectrum (CI, m/z): 181 (M+1), 183 (M+3). Calcd. for C5H9O2Br: C, 33.17; H, 5.02. Found: C, 32.62; H, 4.85.
Reference：
[1] Helvetica Chimica Acta, 1980, vol. 63, # 8, p. 2508 - 2514
[2] Canadian Journal of Chemistry, 2003, vol. 81, # 8, p. 937 - 960
[3] Patent: US2003/232820, 2003, A1, . Location in patent: Page 13
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 336 - 343
[5] Chemistry - An Asian Journal, 2018, vol. 13, # 4, p. 409 - 412
[6] Archiv der Pharmazie (Weinheim, Germany), 1958, vol. 291, p. 23,25, 32
[7] Synthesis, 1982, # 11, p. 963 - 965
3
[ 67-56-1 ]
[ 2623-87-2 ]
[ 4897-84-1 ]
Yield
Reaction Conditions
Operation in experiment
100%
at 0 - 20℃; for 18 h; Inert atmosphere
Acetyl chloride (576 mg, 550 μL, 7.34 mmol) was added to a solution of 4-bromobutyric acid 4 (5.00 g, 30.0 mmol) in methanol (40 mL) cooled to 0 °C. The resulting solution was allowed to warm to room temperature and stirred for 18 h. The solution was evaporated under reduced pressure to yield methyl 4-bromobutanoate 5 (5.40 g, 30.0 mmol quant.) as acolourless oil, which was used without any further purification
85%
at 0 - 20℃; Inert atmosphere
Example 29: Synthesis of 4- (nitrooxy) butanoic acidO oNo2 STEP A: methyl 4-bromobutanoateTo a solution of 4-bromobutanoic acid (6.5 g, 38.9 mmol) in MeOH (120 mL) at 0°C under nitrogen atmosphere, thionyl chloride (2.8 mL, 38.9 mmol) was slowly added and the reaction was stirred overnight at room temperature Solvent was evaporated and the crude material was used directly in next step. (6.0 g, 85percent) H-NMR (CDCI3) : 3.71 (3H,s); 3.49 (2H,t J=6.44); 2.53 (2H,t J=7.16) ; 2.20 (2H,m) .
70%
for 16 h; Reflux; Inert atmosphere
General procedure: Typical procedure: After refluxing the mixture of 4a (7.64g, 45.7mmol), methanol (78.4mL), and conc. sulfuric acid (0.77mL) for 16h under a dry argon atmosphere, it was cooled to room temperature. Then, aqueous solution of sodium bicarbonate (78mL) was added to the reaction mixture and the crude product was extracted with ethyl acetate. After washing the combined organic layer with sodium bicarbonate aqueous solution, water, and brine, it was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluted with a mixed solvent of chloroform/methanol (10/1v/v). The fraction with an Rf value of 0.86 was collected and dried under reduced pressure to afford methyl 4-bromobutanoate (5a) as yellow oil (5.82g, 70percent). (0016) 1H NMR (400MHz, CDCl3, ppm): δ 2.18 (quint, J=7.0Hz, 2H, BrCH2CH2), 2.52 (quint, J=7.1Hz, 2H, Br(CH2)2CH2), 3.47 (t, J=6.4Hz, 2H, BrCH2CH2), and 3.69 (s, 3H, OCH3). 13C NMR (100MHz, CDCl3, ppm): δ 27.70 (BrCH2CH2), 32.18 (Br(CH2)2CH2), 32.68 (BrCH2), 51.71 (OCH3), and 172.98 (COOCH3). IR (NaCl, cm−1): 1738 (C=O)
Reference：
[1] Tetrahedron, 2014, vol. 70, # 44, p. 8343 - 8347
[2] Chemistry - An Asian Journal, 2011, vol. 6, # 1, p. 122 - 127
[3] Patent: WO2011/92065, 2011, A1, . Location in patent: Page/Page column 75-76
[4] Journal of Pharmacology and Experimental Therapeutics, 2016, vol. 357, # 2, p. 240 - 247
[5] Journal of the American Chemical Society, 2018, vol. 140, # 17, p. 5805 - 5813
[6] Heterocycles, 2017, vol. 94, # 8, p. 1518 - 1541
[7] Reactive and Functional Polymers, 2016, vol. 99, p. 1 - 8
[8] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1886, vol. 102, p. 369[9] Bulletin de la Societe Chimique de France, 1886, vol. <2>46, p. 65
[10] Tetrahedron, 2000, vol. 56, # 41, p. 8083 - 8094
[11] Journal of Organometallic Chemistry, 2009, vol. 694, # 3, p. 323 - 331
[12] Organic and Biomolecular Chemistry, 2009, vol. 7, # 9, p. 1821 - 1828
[13] Patent: WO2011/101245, 2011, A1, . Location in patent: Page/Page column 55
[14] Chemical Communications, 2012, vol. 48, # 46, p. 5793 - 5795
[15] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 22, p. 6981 - 6995
[16] Journal of the American Chemical Society, 2017, vol. 139, # 44, p. 15576 - 15579
4
[ 67-56-1 ]
[ 927-58-2 ]
[ 4897-84-1 ]
Yield
Reaction Conditions
Operation in experiment
99%
at 0 - 20℃; Inert atmosphere
4-Bromobutanoyl chloride (3.1 ml, 25.28 mmol) was added to 15 ml of dry metanol at 00C. Stirring was continued at 00C under Ar for 2 h then at RT overnight. The mixture was evaporated, diluted with EtAc/Hexane (1 :5), filtered through SiO2 gel, and evaporated to afford 4.50 g (99percent) of the title compound. . 1H NMR (CDCl3) 3.65 (s, 3H), 3.43 (t, 2H, J = 6.5 MHz), 2.47 (t, 2H, J = 7.1 MHz), 2.13 (dt, 2H, J = 6.7, 13.6 MHz); 13C NMR 173.08, 51.84, 32.82, 32.34, 27.89; MS m/z+ 203.0 (M + Na).
Reference：
[1] Journal of Organic Chemistry, 1997, vol. 62, # 5, p. 1348 - 1355
[2] Patent: WO2010/91150, 2010, A1, . Location in patent: Page/Page column 153
5
[ 2623-87-2 ]
[ 77971-32-5 ]
[ 4897-84-1 ]
Yield
Reaction Conditions
Operation in experiment
83.4%
at 0 - 25℃; for 72.5 h;
4-Bromobutanoic acid (7.5 g, 45.2 mmole) was dissolved in methanol (50 mL), and then CH3SiCl(11.4 mL, 90.4 mmole) was added at 0 °C; the mixture was stirred at this temperature for 30 min andfor 72 h at 25 °C. The solvent was removed in vacuuo. The resultant residue was purified by columnchromatography (silica-gel) eluting with hexanes:ethyl acetate 90:10 to afford the title compound as acolorless oil (6.78 g, 83.4percent). 1H-NMR (CDCl3): δ 3.68 (s, 3H), 3.46 (t, J = 6.4 Hz, 2H), 2.50 (t, J = 7.2 Hz,2H), 2.22–2.13 (m, 2H). 13C-NMR (CDCl3): δ173.11, 51.85, 32.80, 32.34, 27.87. HRMS (FAB+): m/z [M]+calcd for C5H9BrO2: 179.9786, found (M + 1): 180.9786.
Reference：
[1] Molecules, 2018, vol. 23, # 11,
6
[ 67-56-1 ]
[ 2969-81-5 ]
[ 4897-84-1 ]
Reference：
[1] Angewandte Chemie - International Edition, 2001, vol. 40, # 19, p. 3672 - 3674
7
[ 74-85-1 ]
[ 96-32-2 ]
[ 4897-84-1 ]
Reference：
[1] Journal of the American Chemical Society, 1957, vol. 79, p. 5790
[2] Patent: US2880220, 1956, ,
8
[ 64072-44-2 ]
[ 4897-84-1 ]
Reference：
[1] Journal of Organic Chemistry, 1969, vol. 34, p. 3332 - 3335
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In isopropyl alcohol; for 4h;Heating / reflux;
[METHYL 4- (2-OXO-6-HYDROQUINOLYLOXY)] butanoate : Methyl 4-bromobutyrate (6.8 g) was added drop-wise with stirring to a solution of 5 g of <strong>[19315-93-6]6-hydroxyhydroqionoline-2-one</strong> and 7 g of 1, 8-diazabicyclo [5.4. 0] [UNDEC-7-ENE] (DBU) in 75 mL of isopropanol, and refluxed for 4 hours. After cooling and removal of the solvent under vacuum, the residue was dissolved in methylene chloride and the organic phase was washed successively with [0.] 5N [NAOH,] diluted HCl and water, dried over [MGS04,] and concentrated. Re-crystallization of the crude product from water furnished the substituted [QUINOLONE] as colorless [NEEDLES,'H] NMR (400 MHz; [CDC13)] : [8] 7.48 [(M,] 1H); 7.36 (d, 1H); 6.79 [(M,] 1H) ; 6.63 [(M,] 1H); 6.57 (d, 1H); 3.94 [(M,] 2H); 3.67 (s, 3H); 2.25 [(M,] 2H); 2.10 [(M,] 2H).
With triethylamine; In N,N-dimethyl-formamide; at 20℃;
Step l :3-[4-(4-Hydroxy-phenyl)-piperazin-l-yl]-butyric acid methyl ester:; To a mixture of 4-piperazin-l-yl-phenol (2 g, 11.2 mmol) and methyl 3-bromo-butyrate (2.03 g, 11.2 mmol) in DMF (5 mL) was added triethylamine (4.5 mL, 11.53 mmol) dropwise and the reaction mixture was stirred at ambient temperature overnight. The mixture was poured onto water and extracted with ethyl acetate (50 ml x 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and evaporated under vacuum to dryness. The residue was purified by silica gel flash chromatography (1% methanol in CH2Cl2) to furnish the title compound (1.85 g, 59.3%); MS; m/z 279 (M + H).
With potassium carbonate; In N,N-dimethyl-formamide;
Step 1c Preparation of the Nitropyrazole 4. <strong>[26621-44-3]3-Nitropyrazole</strong> (1.13 g, 10 mmol) in dry DMF (10 ml), under argon, was treated with anhydrous K2CO3 (2.7 g, 15 mmol) and then, dropwise, with methyl-4-bromobutyrate (1.82 g, 10.05 mmol) at RT. After stirring overnight the DMF was removed and the residue partitioned between H2O and EtOAc. The combined organic extracts were washed (H2O and brine), dried (Na2SO4), filtered and evaporated to give a mixture of 4 and 6 (2.05 g) as a pale yellow oil. MS (ES+) m/z 214 (MH+).
EXAMPLE 1 Method for Alkylation of <strong>[3316-09-4]4-nitrocatechol</strong> to Give Nitrophenol (18) Sodium hydride (5.2 g of a 60% suspension in oil; 129 mmol) was suspended in DMF (50 cm3) and cooled to 0 C. 4-Nitrocatechol (10 g; 64.5 mmol) in DMF (50 cm3) was slowly added. The purple solution that formed was stirred for 0.5 h and then methyl 4-bromobutyrate (7.4 cm3; 64.5 mmol) was added. The reaction mixture was very viscous for about 1 h but after this time it became quite fluid. The mixture was stirred for 24 h by which time it had become red in colour. The reaction mixture was quenched by careful addition of water and then acidified with 2N hydrochloric acid causing the mixture to tumn pale yellow. The mixture was extracted with ethyl acetate (*2) and the combined extracts,washed with brine (*2), saturated, aqueous sodium bicarbonate, brine, dried (MgSO4) and concentrated under reduced pressure. The yellow sticky solid was washed with hexane to remove mineral oil and gave the nitrophenol (18) (15 g, 67%) as a pale yellow solid. MS (ES+) 256.4 (M+H)+
With triethylamine; In dichloromethane; at 20℃; for 72h;
Preparation of Intermediates 10, 11 and 12Step lMethyl 4-(heptyl[methyl]amino)butanoate: To a solution of methyl 4-bromobutyrate (1.80 mL, 14.3 mmol) in CH2Cl2 (5 mL) was added triethylamine (2.10 mL, 15.0 mmol), followed by N-heptylmethylamine (2.64 mL, 15.7 mmol). After stirring for 3 d at room temperature, the reaction mixture was filtered. The organic layer was washed with water, dried (MgSO4), filtered, and concentrated under reduced pressure to leave a pale yellow oil (2.69 g, 82 %).The crude product was used without purification. 1H NMR (CDCl3, 300 MHz): delta = 0.88 (t, br., J= 6.7 Hz, 3 H, -CH2CH3), 1.22-1.35 (m, 8 H, -(CH^CH,), 1.43 (m, 2 H, NCH2CH2-),1.78 (m, 2 H, -COCH2CH2-), 2.19 (s, 3 H, NCH3), 2.26-2.38 (m, 6 H, -COCH2-, 2 x NCH2-),3.67 (s, 3 H, -OCH3).
With potassium carbonate; In acetonitrile; at 86℃; for 18h;
Compound 28:[228] To a solution of 5-nitro-m-xylene-alpha,alpha'-diol 25 (564 mg, 3.08 mmol) in methanol (35 mL) was added Pd/C (10percent, 164 mg, 0.154 mmol). Hydrogen was introduced to replace the air then the mixture was hydrogenated (H2, 5 psi) for 2 hours at room temperature. The solution was filtered through celite and the filtrate was evaporated by rotary evaporation in vacuo to give compound 26, which was dissolved in anhydrous acetonitrile (15 mL) and methyl 4- bromobutyrate (557 mg, 3.08 mmol) and potassium carbonate (426 mg, 3.08 mmol) were added. The mixture was put in a 86 0C oil bath and refluxed for 18 hours. The reaction mixture was removed from the oil bath, cooled to room temperature and diluted with dichloromethane. It was filtered through celite and the solid was washed with dichloromethane/acetonitrile (1 :1). The filtrate was evaporated under reduced pressure and the residue was purified through silica gel chromatography (Combiflash, dichloromethane/methanol) to give compound 28 (292 mg, y = 37percent) as a white solid. 1H NMR (400 MHz, MeOD): delta 6.62 (s, IH), 6.55 (s, 2H), 4.50 (s, 4H), 3.65 (s, 3H), 3.13 (d, J = 7.2 MHz, 2H), 2.43 (d, J = 7.2 MHz, 2H), 1.89 (p, J = 7.2 MHz, 2H); 13C NMR (400 MHz, MeOD): delta 175.9, 150.5, 143.7, 115.5, 111.7, 65.7, 52.2, 44.3, 32.5, 25.8; MS (m/z): found 276.0 (M + Na)+.
A solution of LDA (1.07 mmol, 1.1 equiv) [prepared from diisopropylamine (0.15 mL, 1.07 mmol) in THF (2.5 mL) and n-BuLi (1.5 M in hexane, 0.7 mL, 1.07 mmol) stirred at -78 C for 30 min] was added to a solution of 4 (200 mg, 0.97 mmol, 1 equiv) in THF (1.4 mL), cooled to -78 C. The reaction mixture was allowed to warm up to -65 C (l h), cooled again to -78 C and a mixture of methyl 4-bromobutyrate (0.37 mL, 2.92 mmol, 3 equiv) and HMPA (1.1 mL, 6.14 mmol, 6.3 equiv) in THF (2.3 mL) was added. The solution was allowed to warm to rt and then stirred for 16 h. Then the reaction was quenched with saturated aqueous NH4Cl and was extracted with Et2O (3×3 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (AcOEt/petroleum ether, 1:9 to 1:1) to afford 17 (32 mg, 11%) as a yellow oil. TLC Rf 0.66 (silica gel, AcOEt/petroleum ether, 1:2); IR (film) 1733 cm-1; 1H NMR (300 MHz, CDCl3) delta 7.34-7.16 (m, 5H, Ph), 3.76 (s, 3H, CO2Me), 3.68 (d, 1H, J=12.9 Hz, CH2Ph), 3.67 (s, 3H, CO2Me), 3.59 (d, 1H, J=12.9 Hz, CH2Ph), 3.20-3.08 (m, 2H, H-4), 2.52 (m, 1H, H-3a), 2.34 (t, 2H, J=7.4 Hz, H-3'), 2.02 (m, 1H, H-3b), 1.92 (dd, 1H, J=11.6, 5.2 Hz, H-1'a), 1.82 (m, 1H, H-1'b), 1.67 (m, 1H, H-2'a), 1.53 (m, 1H, H-2'b); 13C NMR (75 MHz, CDCl3) delta 173.8 (2 CO), 138.5 (Cq-Ar), 128.6 (2CH-Ar), 128.3 (2CH-Ar), 127.0 (1CH-Ar), 72.1 (C-2), 56.1 (CH2Ph), 51.7 (OCH3), 51.6 (OCH3), 49.8 (C-4), 34.2 (C-1' or C-3'), 34.0 (C-1' or C-3'), 26.0 (C-3), 19.6 (C-2'); HRMS (ESI) [M+Na]+ calcd for C17H23NO4Na: 328.152, found 328.151.
methyl 4-[2-(methylamino)benzimidazol-1-yl]butanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
28%
With caesium carbonate; In acetonitrile; at 20℃;
To a solution of <strong>[17228-38-5]N-methyl-1H-benzimidazol-2-amine</strong> (1.36 g, 9.24 mmol, 1.00) in acetonitrile (40 mL) was added cesium carbonate (12 g, 37.0 mmol, 4 equiv) followed by methyl 4-bromobutanoate (1.40 mL, 2.01 g, 11.1 mmol, 1.0 equiv). The reaction mixture was stirred overnight at RT, then was filtered through Celite and concentrated to dryness in vacuo. The residue was purified by flash column chromatography (silica gel, 100-200 mesh, 0 to 10% methanol in dichloromethane) to afford methyl 4-[2-(methylamino)benzimidazol-1-yl]butanoate (0.65 g, 28%) as an orange oil. LCMS (5 to 95% acetonitrile in water + 0.1% formic acid over 2 mins) retention time 0.88 min, ESI+ found [M+H]
methyl 4-(4-oxo-6-propyl-1,4-dihydropyrimidin-2-ylthio)butanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
47%
With potassium carbonate; In methanol; water;Reflux;
To a solution of thiouracil 7 (0.85 g, 5 mmol) and potassium carbonate (1.03g, 7.5 mmol) in methanol (5 mL) and water (10 mL) was added methyl 4-bromobutanoate (1.36g, 7.5 mmol). The solution was heated to reflux overnight. The reaction mixture was cooled to room temperature, 50 mL water was added, and the mixture was extracted with ethyl acetate (3 x 50 mL). The organic layers were combined and washed with water (50 mL) and brine (50 mL), dried over MgS04, the solvent was removed by rotary evaporator. The crude product was purified by flash column chromatography on silica gel using MeOH/DCM as eluent to give methyl 4-(4-oxo-6-propyl- l,4-dihydropyrimidin-2-ylthio)butanoate as white solid (0.64 g, 47% yield): mp. 129- 130 C; 1H NMR (500 MHz, CDC13) delta 0.95 (t, J = 7.0 Hz, 3H), 1.64-1.71(m, 2H), 2.06 (m, 2H), 2.46 (m, 4H), 3.24 (t, J = 7.0 Hz, 2H) , 3.68 (s, 3H) , 6.04 (s, 1H), 12.99 (s, 1H); 13C NMR (125 MHz, CDC13) delta 13.8, 21.0, 24.7, 29.9, 32.7, 39.7, 51.8, 108.0, 160.2, 165.6, 169.5, 173.4; HRMS (ESI+) calcd for C12H19N2O3S [M + H]+ 271.1111, found 271.111(Delta= 0.51ppm).
Methyl 4-(3-bromo-5-fluorophenoxy)butanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With potassium carbonate;
Step 1: Methyl 4-(3-bromo-5-fluorophenoxy)butanoate To a solution of <strong>[433939-27-6]3-bromo-5-fluoro-phenol</strong> (5.24 mmol, 1.0 g) in acetone (20 mL) was added potassium iodide (0.26 mmol, 43 mg), potassium carbonate (5.76 mmol, 800 mg) and methyl 4-bromobutanoate (5.76 mmol, 0.73 mL). The reaction was heated at reflux overnight. The mixture was partitioned between ethyl acetate and water and the phases were separated. The aqueous layer was extracted with ethyl acetate, the organic extracts were combined, washed with brine, dried over sodium sulfate and the solvent was evaporated. The residue was purified by silica gel chromatography (solvent gradient: 0-30% ethyl acetate in heptanes) to afford 1370 mg (90%) of the title compound.
8-fluoro-7-methyl-3,4-dihydrobenzo[b]oxepin-5(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
To a solution of <strong>[452-78-8]3-fluoro-4-methylphenol</strong> (5 g, 39.64 mmol) in DMF (50 ml), was added potassium carbonate (6.03 g, 43.61 mmol). After 10 minutes of stirring at room temperature, methyl-4-bromobutyrate (8.31 g, 43.61 mmol) was added. The white suspension was heated at 50C for 24 hours. After cooling to room temperature, MeOH (75 ml), water (50 ml) and sodium hydroxide 32% (25 ml) were added. The reaction mixture was heated at 90C for 1 hour. After cooling to room temperature, ice (400 g) was added, then HCI 5N was added to pH 3. The solid was filtered, washed with water (3x50 ml) and dried by heating under reduced pressure over P205. To the obtained yellow powder, polyphosphoric acid (PPA, 130 g) was added, then the mixture was heated at 80C for 1 hour. Ice was slowly added and the precipitate was filtered, and dried under reduced pressure over P205 to give 5.86 g (77%) of 8-fluoro-7-methyl-3,4- dihydrobenzo[b]oxepin-5(2H)-one as a yellow solid. LC/MS (m/z, MH+): 195
8-fluoro-9-methyl-3,4-dihydrobenzo[b]oxepin-5(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
To a solution of <strong>[443-87-8]2-methyl-3-fluorophenol</strong> (5 g, 39.64 mmol) in DMF (60 ml), was added potassium carbonate (6.03 g, 43.61 mmol). After 10 minutes of stirring at room temperature, methyl-4-bromobutyrate (8.31 g, 43.61 mmol) was added. The white suspension was heated at 50C for 24 hours. After cooling to room temperature, MeOH (50 ml), water (50 ml) and sodium hydroxide 32% (30 ml) were added. The reaction mixture was heated at 80C for 30 minutes. After cooling to room temperature, ice (100 g) was added, then HCI 5N was added to pH 3. The solid was filtered, washed with water (3x50 ml) and dried by heating under reduced pressure over P205. To the obtained white powder, polyphosphoric acid (PPA, 100 g) was added, then the mixture was heated at 90C for 15 minutes. Ice (300 g) was slowly added and the precipitate was filtered, and dried under reduced pressure over P205 to give 6.64 g (86%) of 8-fluoro-9-methyl-3,4- dihydrobenzo[b]oxepin-5(2H)-one as a yellow solid. LC/MS (m/z, MH+): 195
methyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]butanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With caesium carbonate; In acetonitrile; at 20 - 130℃;Microwave irradiation;
To a stirred solution of 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (200 mg, 1.03 mmol, 1 eq.) in ACN (5 mL) are added methyl 4-bromobutanoate (143 pL, 1.13 mmol, 1.1 eq.), CS2CO3 (440 mg, 1.33 mmol, 1.3 eq.) and the reaction mixture is stirred at 120 C for 20 min (microwave heating) then at 130 C for 10 min. Methyl 4-bromobutanoate (26 pL, 0.21 mmol, 0.2 eq.) is added and the reaction mixture is stirred at 120 C for 1 h then at RT overnight. The mixture is concentrated in vacuo, water and DCM are added. The mixture is extracted with DCM, dried by filtration over hydrophobic column and concentrated in vacuo to afford the expected product.
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