* 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.
Example 7; 2-Amino-1-ethyl-4-oxo-7-[4-(3-pyridin-3-ylmethylureido)phenyl]-1,4-dihydroquinoline-3-carboxylic Acid Amide (No. 57)7.1: 7-Bromo-1H-benzo[d][1,3]oxazine-2,4-dione In a 250 ml round-bottomed flask, under a nitrogen atmosphere, 5.0 g (23.1 mmol) of 2-amino-4-bromobenzoic acid are dissolved in 50 ml of anhydrous dioxane. The temperature of the mixture is reduced to 0° C. by means of an ice bath. 2.3 g (7.6 mmol) of triphosgene are added dropwise. The ice bath is replaced with an oil bath and the mixture is refluxed for 16 h. After a return to ambient temperature, water (100 ml) is added and the precipitate formed is filtered off, washed with Et2O (3.x.25 ml) and then dried in an oven, so as to obtain 5.6 g (23.1 mmol) of the compound in the form of a beige powder. Yield=100percent. 1H NMR DMSO d6 (300 MHz) 7.29 (d, J=1.8 Hz, 1H); 7.41 (dd, J=8.4 Hz, J=1.8 Hz, 1H); 7.82 (d, J=8.4 Hz, 1H); 11.81 (bs, 1H).
95.8%
at 0 - 110℃; for 16 h;
Step 1 : To a solution of 2-amino-4-bromobenzoic acid (4 g, 18.51 mmol) in 1,4-dioxane (40 mL) was added bis(trichloromethyl)carbonate in 1,4-dioxane (1.81 g, 6.11 mmol) drop wise at 0 °C. The reaction mixture was stirred at 110 °C for 16 h. The solvent was evaporated under reduced pressure and washed with n-hexane to afford 7-bromo-lH- benzo[d][l,3]oxazine-2,4-dione (4.3 g, 95.8percent LC-MS 97percent).]H NMR: (400 MHz, DMSO- d6) S (ppm) 11.8 (s, 1H), 7.80 (d, J= 8.4 Hz, 1H), 7.40 (d, J= 8.4 Hz, 2H); MS (ESI) m/z 243.02 [C8H4BrN03+H]+.
95.8%
at 0 - 110℃; for 16 h;
To a solution of 2-amino-4-bromobenzoic acid (4 g, 18.51 mmol) in 1,4-dioxane (40 mL) was added bis(trichloromethyl)carbonate in 1,4-dioxane (1.81 g, 6.11 mmol) drop wise at 0° C. The reaction mixture was stirred at 110° C. for 16 h. The solvent was evaporated under reduced pressure and washed with n-hexane to afford 7-bromo-1H-benzo[d][1,3]oxazine-2,4-dione (4.3 g, 95.8percent LC-MS 97percent). H NMR: (400 MHz, DMSO-d6) δ (ppm) 11.8 (s, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.40 (d, J=8.4 Hz, 2H); MS (ESI) m/z 243.02 [C8H4BrNO3+H]+.
89%
at 70℃; for 12 h;
General procedure: A 500 mL single neck round-bottomed flask equipped with a football-shaped PTFE stirring bar (16 mm × 37 mm) was chargedwith 2-amino-5-bromobenzoic acid (10.0 g, 46.3 mmol,1.0 equiv) followed by the addition of tetrahydrofuran (230 mL,0.2 molar) and solid triphosgene (13.7 g, 46.3 mmol, 1.0 equiv)resulting in a suspension. The reaction vessel was placed into afitted metal heating mantle and the neck was equipped with a24/40 Liebig condenser. The suspension was stirred (500 rpm)and the heating mantle set to 70 °C. The suspension becamehomogenous before a white solid precipitated out after about30 minutes at 70 °C. The heterogeneous reaction mixture wasaged for 12 hours then cooled to room temperature (25 °C). Theslurry was poured into a 600 mL beaker equipped with overheadmechanical stirrer (PTFE 75 mm paddle) containing250 mL of deionized water. With vigorous stirring, the mixturebecame homogenous followed by precipitation of a pale whitesolid. The solid was collected by vacuum filtration on aBüchner funnel (7.6 cm diameter) with Whatman 1 filter paper(70 mm) and air pulled through for 5 minutes. The material was transferred to a 250 mL Erlenmeyer flask equipped with cylindricalstir bar and 50 mL of methanol was added. The slurrywas stirred for 10 minutes and then collected by vacuum filtration.The filter cake was dried under vacuum (0.1 mmHg at 25 °C) for 12 hours to afford 9b as a white powder (90percent yield).
68%
at 80℃; Inert atmosphere
The 2-amino-4-bromobenzoic acid (10.0g, 46 . 3mmol) dissolved in tetrahydrofuran (100 ml) in, adding triphosgene (4.54g, 15 . 3mmol), under the protection of nitrogen is heated to 80 °C stirring overnight. Cooling to room temperature, the reaction solution the ice water (120 ml) in, filtering, the filter cake are sequentially water, ether washing, drying, to obtain brown solid (7.60g, 68.0percent).
Reference：
[1] Patent: US2011/251194, 2011, A1, . Location in patent: Page/Page column 17
[2] Patent: WO2013/147711, 2013, A1, . Location in patent: Page/Page column 158
[3] Patent: US2014/371199, 2014, A1, . Location in patent: Paragraph 0584
[4] Beilstein Journal of Organic Chemistry, 2018, vol. 14, p. 2529 - 2536
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 17, p. 6928 - 6937
[6] Patent: CN105384687, 2016, A, . Location in patent: Paragraph 0268; 0269; 0271; 0272; 0273
[7] Patent: WO2011/75699, 2011, A2, . Location in patent: Page/Page column 104
[8] Journal of Agricultural and Food Chemistry, 2015, vol. 63, # 31, p. 6883 - 6889
[9] Patent: EP3357916, 2018, A1, . Location in patent: Paragraph 0085
2
[ 6326-79-0 ]
[ 76561-16-5 ]
Reference：
[1] Catalysis Science and Technology, 2015, vol. 5, # 10, p. 4830 - 4838
[2] Patent: US5599814, 1997, A,
c. 7-Bromo-2H-3,1-benzoxazine-2,4(1H)-dione Using a procedure similar to that described in Example 13c. except starting with 6-bromo-1H-indole-2,3-dione, the title compound was obtained (82%) as a yellow solid, mp 280-281 C.; MS(CI): 242, 244 (M+H).
d. Diethyl 7-bromo-4-hydroxyquinoline-2,3-dicarboxylate To a stirred mixture of diethyl oxosuccinate sodium salt (1.31 g, 6.23 mM) in dimethylformamide (DMF, 15 mL) under a nitrogen atmosphere was added a solution of <strong>[76561-16-5]7-bromo-2H-3,1-benzoxazine-2,4(1H)-dione</strong> (1.50 g, 6.20 mM) in DMF (15 mL). The resulting reaction mixture was heated to 130 C. over 2.5 hr and then refluxed for 5 hr. After cooling to room temperature, the reaction mixture was concentrated and the residue was chromatographed over silica gel (eluant: ethyl acetate/methylene chloride; 5/95). The fractions containing the desired material were combined and concentrated. The solid residue was recrystallized from ethanol/ether to provide (0.54 g, 24%) the title compound as a tan solid, mp 233.5-234.5 C.; MS(CI): 368, 369 (M+H). Analysis for C15 H14 BrNO5. 0.3 H2 O: Calculated: C, 48.22; H, 3.93; N, 3.74 Found: C, 48.13; H, 3.80; N, 3.68
1-(2-amino-4-bromophenyl)-2-(1-methyl-1H-tetrazol-5-yl)ethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With n-butyllithium; In tetrahydrofuran; hexane; water;
(a) A solution of butyl lithium in hexane (2.7M, 104 ml) was added slowly to a stirred solution of 1,5-dimethyltetrazole (27.5 g) in dry tetrahydrofuran (500 ml) at -5 to 0 under nitrogen. After stirring for 1.5 hours, <strong>[76561-16-5]7-bromo-1H-3,1-benzoxazine-2,4-dione</strong> (22.6 g) was added and stirring continued for 18 hours at room temperature and for 3.5 hours at 40 to 50. The mixture was cooled to room temperature, industrial methylated spirit (15 ml) added and most of the solvents distilled off. The residue was added to water (200 ml) and acidified with 5N hydrochloric acid to pH 1. The resulting solid was collected by filtration and crystallized from ethyl acetate to give the novel compound 1-(2-amino-4-bromophenyl)-2-(1-methyl-1H-tetrazol-5-yl)ethanone, m.p. 159-160.
Sodium hydride (0.47 g, 12 mmol) was added to a 3 neck 250 mL RBF under nitrogen and then washed with hexanes. Once the hexanes were decanted, N,N-dimethylformamide (20.0 mL, 11 mmol) was added. The resulting mixture was cooled to 0 C. using an ice-water bath, and then <strong>[76561-16-5]7-bromo-1H-benzo[d][1,3]oxazine-2,4-dione</strong> (2.7 g, 11 mmol) was added in one batch. After stirring at room temperature for 1 hour, iodomethane (0.70 mL, 11 mmol) was added dropwise to the yellow solution, and the reaction mixture was stirred for 16 hours. Water (50 mL) was added, and the resulting precipitate that formed was collected via filtration. The solid washed with additional water (100 mL), followed by ether (100 mL). Drying in a vacuum oven overnight at 50 C. afforded the desired product as an off-white solid (2.1 g, 74% yield).
74%
(b) 7-Bromo-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione.Sodium hydride (0.47 g, 12 mmol) was added to a 3 neck 250 mL round bottom flask under nitrogen and then washed with hexanes. Once the hexanes were decanted, DMF (20.0 mL, 1 1 mmol) was added. The resulting mixture was cooled to 0C using an ice-water bath, and then 7-bromo-1H- benzo[d][1,3]oxazine-2,4-dione (2.7 g, 11 mmol) was added in one batch. After stirring at room temperature for 1 hour, iodomethane (0.70 mL, 11 mmol) was added dropwise to the yellow solution, and the reaction mixture was stirred for 16 hours. Water (50 mL) was added, and the resulting precipitate that formed <n="58"/>was collected via filtration. The solid was washed with additional water (100 mL), followed by ether (100 mL). Drying in a vacuum oven overnight at 50C provided the title compound as an off-white solid (2.1 g, 74% yield).
47.5%
Under the protection of nitrogen, to three-port in the round-bottom flask is added sodium hydride (0.54g, 13 . 50mmol) and N, N-dimethylformamide (20 ml), cooled to 0 C, by adding 7-bromo -1H-benzo [d] [1,3] oxazine -2,4-dione (2.70g, 11 . 00mmol), stir at room temperature 1 hour, iodomethane dropwise is added to the reaction mixture(760muL, 12 . 00mmol), continuing to stir at room temperature 16 hours. Reaction liquid the ice water (50 ml) in, filtering, the filter cake are sequentially water, ether washing, drying, to obtain brown solid (1.36g, 47.5%).
(a) 7-Bromo-1H-benzo[d][1,3]oxazine-2,4-dione. In a 250 mL round-bottom flask under N2 was dissolved 2-amino-4-bromobenzoic acid (available from Aldrich)(l 1.69 g) in 100 mL of 1,4-dioxane. The solution was cooled to 0C and phosgene (36 mL, 68 mmol) was added to this solution via a dropping funnel. The reaction mixture was stirred for 24 hours allowing to warm to 23C (room temperature). The resulting white solid was filtered off and washed with 1,4-dioxane and Et2O.
Methylamine (40% in water, 2 mL, 23.1 mmol) was added dropwise after the mixture was cooled to room temperature. After stirring for 30 min, the solution was evaporated under reduced pressure and the residue was redissolved in DCM which was washed with sat. NaHC03 aqueous solution, dried over Na2S04, filtered, and evaporated to give 4.6 g of the target compound. MS (ESI): 229, 231 (MH+).
In 1,4-dioxane; at 0℃; for 16h;Inert atmosphere; Reflux;
Example 7; 2-Amino-1-ethyl-4-oxo-7-[4-(3-pyridin-3-ylmethylureido)phenyl]-1,4-dihydroquinoline-3-carboxylic Acid Amide (No. 57)7.1: 7-Bromo-1H-benzo[d][1,3]oxazine-2,4-dione In a 250 ml round-bottomed flask, under a nitrogen atmosphere, 5.0 g (23.1 mmol) of 2-amino-4-bromobenzoic acid are dissolved in 50 ml of anhydrous dioxane. The temperature of the mixture is reduced to 0 C. by means of an ice bath. 2.3 g (7.6 mmol) of triphosgene are added dropwise. The ice bath is replaced with an oil bath and the mixture is refluxed for 16 h. After a return to ambient temperature, water (100 ml) is added and the precipitate formed is filtered off, washed with Et2O (3×25 ml) and then dried in an oven, so as to obtain 5.6 g (23.1 mmol) of the compound in the form of a beige powder. Yield=100%. 1H NMR DMSO d6 (300 MHz) 7.29 (d, J=1.8 Hz, 1H); 7.41 (dd, J=8.4 Hz, J=1.8 Hz, 1H); 7.82 (d, J=8.4 Hz, 1H); 11.81 (bs, 1H).
95.8%
In 1,4-dioxane; at 0 - 110℃; for 16h;
Step 1 : To a solution of 2-amino-4-bromobenzoic acid (4 g, 18.51 mmol) in 1,4-dioxane (40 mL) was added bis(trichloromethyl)carbonate in 1,4-dioxane (1.81 g, 6.11 mmol) drop wise at 0 C. The reaction mixture was stirred at 110 C for 16 h. The solvent was evaporated under reduced pressure and washed with n-hexane to afford 7-bromo-lH- benzo[d][l,3]oxazine-2,4-dione (4.3 g, 95.8% LC-MS 97%).]H NMR: (400 MHz, DMSO- d6) S (ppm) 11.8 (s, 1H), 7.80 (d, J= 8.4 Hz, 1H), 7.40 (d, J= 8.4 Hz, 2H); MS (ESI) m/z 243.02 [C8H4BrN03+H]+.
95.8%
In 1,4-dioxane; at 0 - 110℃; for 16h;
To a solution of 2-amino-4-bromobenzoic acid (4 g, 18.51 mmol) in 1,4-dioxane (40 mL) was added bis(trichloromethyl)carbonate in 1,4-dioxane (1.81 g, 6.11 mmol) drop wise at 0 C. The reaction mixture was stirred at 110 C. for 16 h. The solvent was evaporated under reduced pressure and washed with n-hexane to afford 7-bromo-1H-benzo[d][1,3]oxazine-2,4-dione (4.3 g, 95.8% LC-MS 97%). H NMR: (400 MHz, DMSO-d6) delta (ppm) 11.8 (s, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.40 (d, J=8.4 Hz, 2H); MS (ESI) m/z 243.02 [C8H4BrNO3+H]+.
89%
In tetrahydrofuran; at 70℃; for 12h;
General procedure: A 500 mL single neck round-bottomed flask equipped with a football-shaped PTFE stirring bar (16 mm × 37 mm) was chargedwith 2-amino-5-bromobenzoic acid (10.0 g, 46.3 mmol,1.0 equiv) followed by the addition of tetrahydrofuran (230 mL,0.2 molar) and solid triphosgene (13.7 g, 46.3 mmol, 1.0 equiv)resulting in a suspension. The reaction vessel was placed into afitted metal heating mantle and the neck was equipped with a24/40 Liebig condenser. The suspension was stirred (500 rpm)and the heating mantle set to 70 C. The suspension becamehomogenous before a white solid precipitated out after about30 minutes at 70 C. The heterogeneous reaction mixture wasaged for 12 hours then cooled to room temperature (25 C). Theslurry was poured into a 600 mL beaker equipped with overheadmechanical stirrer (PTFE 75 mm paddle) containing250 mL of deionized water. With vigorous stirring, the mixturebecame homogenous followed by precipitation of a pale whitesolid. The solid was collected by vacuum filtration on aBuechner funnel (7.6 cm diameter) with Whatman 1 filter paper(70 mm) and air pulled through for 5 minutes. The material was transferred to a 250 mL Erlenmeyer flask equipped with cylindricalstir bar and 50 mL of methanol was added. The slurrywas stirred for 10 minutes and then collected by vacuum filtration.The filter cake was dried under vacuum (0.1 mmHg at 25 C) for 12 hours to afford 9b as a white powder (90% yield).
68%
In tetrahydrofuran; at 80℃;Inert atmosphere;
The 2-amino-4-bromobenzoic acid (10.0g, 46 . 3mmol) dissolved in tetrahydrofuran (100 ml) in, adding triphosgene (4.54g, 15 . 3mmol), under the protection of nitrogen is heated to 80 C stirring overnight. Cooling to room temperature, the reaction solution the ice water (120 ml) in, filtering, the filter cake are sequentially water, ether washing, drying, to obtain brown solid (7.60g, 68.0%).
In 1,4-dioxane; for 4h;Reflux;
Example 2.1a. Synthesis of 2-amino-4-bromo-N-methylbenzamideTo a mixture of 2-amino-4-bromobenzoic acid (5.0 g, 23.1 mmol) and dioxane (50 mL) was added triphosgene (2.3 g, 7.75 mmol). The reaction mixture was heated to reflux and stirred for 4 h.
In tetrahydrofuran; for 4h;Reflux;
Compound C (e.g., 4.6mmol) and triphosgene (e.g., 4.6mmol) were added in tetrahydrofuran (e.g., 30mL), heated to reflux for 4 hours and cooled to the room temperature. 5% sodium hydroxide solution (e.g., 50 mL) and ethyl acetate (e.g., 30mL) were added for phase separation. The organic phase was dried and concentrated under reduced pressure to obtain compound D.
7.2: 7-Bromo-1-ethylbenzo[d][1,3]oxazine-2,4-dione; In a 250 ml round-bottomed flask, under a nitrogen atmosphere, 1.0 g (25.5 mmol) of NaH at 60% is suspended in 60 ml of anhydrous DMF. The temperature of the mixture is reduced to 0 C. by means of an ice bath. 5.6 g (23.1 mmol) of the compound of stage 7.1 are added dropwise, and then the mixture is stirred for 3 hours at ambient temperature. 2 ml (25.5 mmol) of iodoethane are added dropwise, and then the mixture is stirred for 16 h at ambient temperature. The mixture is poured into ice-cold water (100 ml) and the precipitate formed is filtered off. It is washed with water (3×25 ml) and then dried in an oven, so as to obtain 5.9 g of product (21.8 mmol) in the form of an off-white powder. Yield=95%. 1H NMR DMSO d6 (300 MHz) 1.20 (t, J=7.1 Hz, 3H); 4.06 (q, J=7.1 Hz, 2H); 7.50 (dd, J=8.4 Hz, J=1.5 Hz, 1H); 7.75 (d, J=1.5 Hz, 1H); 7.90 (d, J=8.4 Hz, 1H).
7-Bromo-1H-benzo[d][1,3]oxazine-2,4-dione (2.00 g, 8.3 mmol)Dissolved in N,N-dimethylformamide (20 mL), sodium hydride (0.40 g, 10.0 mmol) was added portionwise in ice water bath, stirring was continued for 20 min, and ethyl iodide (1.30, 8.3 mmol) was added dropwise to the reaction mixture. The reaction was carried out for 1 h at room temperature, and the reaction was monitored by TLC until the starting material was completely reacted. No post-processing, continuous operation.
With dmap; In N,N-dimethyl-formamide; at 20℃; for 16h;
Step 2: To a solution of 7-bromo- lH-benzo[d][l,3]oxazine-2,4-dione (400 mg, 1.65 mmol), tert-butyl methyl(piperidin-4-yl)carbamate (389 mg, 1.81 mmol) in DMF (5 mL) was added DMAP (20 mg, 0.16 mmol) at rt and the mixture was stirred for 16 h. To the reaction mixture was added ice cooled water and the solid thus precipitated was filtered and washed in turn with water, n-pentane and dried to afford tert-butyl 4-(2-amino-4-bromobenzoyl)piperazine- 1-carboxylate (910 mg, 57%, LC-MS 64.6%). MS (ESI) m/z 384/386 [Ci6H22BrN303+H]+.
With dmap; In N,N-dimethyl-formamide; at 20℃; for 16h;
To a solution of <strong>[76561-16-5]7-bromo-1H-benzo[d][1,3]oxazine-2,4-dione</strong> (400 mg, 1.65 mmol), tert-butyl methyl(piperidin-4-yl)carbamate (389 mg, 1.81 mmol) in DMF (5 mL) was added DMAP (20 mg, 0.16 mmol) at rt and the mixture was stirred for 16 h. To the reaction mixture was added ice cooled water and the solid thus precipitated was filtered and washed in turn with water, n-pentane and dried to afford tert-butyl 4-(2-amino-4-bromobenzoyl)piperazine-1-carboxylate (910 mg, 57%, LC-MS 64.6%). MS (ESI) m/z 384/386 [C16H22BrN3O3+H]+.
With dmap; In N,N-dimethyl-formamide; at 20℃; for 16h;
Step 2: To a solution of 7-bromo-lH-benzo[d][l,3]oxazine-2,4-dione (400 mg, 1.65 mmol), tert-butyl methyl(piperidin-4-yl)carbamate (389 mg, 1.81 mmol) in DMF (5 mL) was added DMAP (20 mg, 0.16 mmol) at rt and stirred at same temperature for 16 h. The reaction mixture was added ice cooled water and extracted with EtOAc (3 *30 mL). The combined organic layer was washed with water, brine solution and dried over Na2S04 and was concentrated under reduced pressure to obtain the crude product. The crude product was washed with n-pentane to afford tert-butyl 1 -(2-amino-4-bromobenzoyl)piperidin-4- yl(methyl)carbamate (670 mg, 98%, LC-MS 94%). 1H NMR (400 MHz, CDC13) delta 6.93 (d, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J= 6.8 Hz, 1H), 4.42 (s, 3H), 4.21 (br s, 2H), 2.95 (s, 2H), 2.88 (s, 3H), 1.72-1.62 (m, 4H), 1.46 (s, 9H); MS (ESI) m/z 412/414 [Ci8H26BrN303 ]+.
With dmap; In N,N-dimethyl-formamide; at 20℃; for 16h;
To a solution of <strong>[76561-16-5]7-bromo-1H-benzo[d][1,3]oxazine-2,4-dione</strong> (400 mg, 1.65 mmol), tert-butyl methyl(piperidin-4-yl)carbamate (389 mg, 1.81 mmol) in DMF (5 mL) was added DMAP (20 mg, 0.16 mmol) at rt and stirred at same temperature for 16 h. The reaction mixture was added ice cooled water and extracted with EtOAc (3*30 mL). The combined organic layer was washed with water, brine solution and dried over Na2SO4 and was concentrated under reduced pressure to obtain the crude product. The crude product was washed with n-pentane to afford tert-butyl 1-(2-amino-4-bromobenzoyl)piperidin-4-yl(methyl)carbamate (670 mg, 98%, LC-MS 94%). 1H NMR (400 MHz, CDCl3) delta 6.93 (d, J=8.4 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J=6.8 Hz, 1H), 4.42 (s, 3H), 4.21 (br s, 2H), 2.95 (s, 2H), 2.88 (s, 3H), 1.72-1.62 (m, 4H), 1.46 (s, 9H); MS (ESI) m/z 412/414 [C18H26BrN3O3]+.
With ammonium carbonate; In 1,4-dioxane; at 60℃; for 8h;
General procedure: A suspension of substituted isatoic anhydride (35 mmol), ammonium carbonate (140 mmol), and 1,4-dioxane (150 mL) was heated at 60 C. After stirring for 8 h, the reaction mixture was cooled to room temperature and evaporated under reduced pressure, and then water (200 mL) was added to the residue, which was extracted with CH2Cl2 (380 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to give compounds 9 in yields of 63-94%.
7-bromo-1-(2-cyclopropylethyl)-1H-benzo[d][1,3]oxazine-2,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
99.11%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 4h;
To the three port round bottom flask, 7-bromo -1H-benzo [d] [1,3] oxazine -2,4-dione (2.00g, 8 . 26mmol), 2-cyclopropyl-ethanol (0.870g, 10 . 1mmol), triphenylphosphine (3.25g, 12 . 4mmol) and tetrahydrofuran (60 ml) were sequentially added and cooled to 0 C, (2.50 ml, 12 . 7mmol), diisopropyl azodicarboxylate added dropwise , to the stirring the mixture at room temperature for 4 hours. Reduced pressure distillation to remove the solvent, the crude product purification column chromatography (petroleum ether/dichloromethane (v/v)=10/1) obtained white solid (2.54g, 99 . 11%).
7-bromo-1-(cyclopropyl-methyl)-1H-benzo[d][1,3]oxazine-2,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44.5%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 5h;Inert atmosphere;
Under nitrogen atmosphere and sirring to 0 C 7-bromo -1H-benzo [d] [1,3] oxazine -2,4-dione (2.39g, 9 . 87mmol), cyclopropyl methanol (0.782g, 10 . 8mmol) and triphenylphosphine (3.88g, 14 . 8mmol) tetrahydrofuran (80 ml) (2.99g, 14 . 8mmol), was added to the solution of diisopropyl azodicarboxylate at 0 C and stirred for 1 hour to room temperature to continue stirring 4 hours. Decompression evaporate the solvent, the crude product purification column chromatography (petroleum ether/ethyl acetate (v/v)=40/1), get white solid (1.30g, 44.5%).
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