Some common heterocyclic compound, 90347-66-3, name is Methyl 3-iodo-4-methylbenzoate, molecular formula is C9H9IO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Safety of Methyl 3-iodo-4-methylbenzoate
A mixture of 19 (1366 mg, 4.63 mmol), (S)-tert-butyl piperidin-3-ylcarbamate (1020mg, 4.63 mmol) and K2CO3 (768 mg, 5.56 mmol) in DMF (8 mL) was stirred at roomtemperature overnight. Water was added and the mixture was extracted with EtOAc twice. Thecombined organic layers were washed with brine, dried over Na2SO4 and concentrated. Theresidue was purified by silica gel column chromatography to give 34 (870 mg, 45%) as aslightly yellow solid. LCMS (m/z: m+1): 414.0, 116.1. A suspension of 34 (870 mg, 2.1 mmol),1 (517 mg, 6.3 mmol), K2CO3 (580 mg, 4.2 mmol), CuI (120 mg, 0.63 mmol) and 8-hydroxyquinoline (61 mg, 0.42 mmol) in DMSO (8 mL) was heated at 120C overnight undernitrogen. After cooling, water was added and the mixture was extracted with EtOAc twice. Thecombined organic layers were washed with brine, dried over Na2SO4 and concentrated. Theresidue was purified by silica gel column chromatography to give 35 (630 mg, 72%) as aslightly yellow solid. LCMS (m/z: m+1): 416.3. A mixture of 35 (630 mg, 1.52 mmol) andSnCl2 2H2O (1369 mg, 6.06 mmol) in EtOH (13 ml) was heated at 80C for 1 h. After cooling,silica gel was added to the reaction and the mixture was concentrated to dryness. The residuewas purified by silica gel column chromatography to give 36 (430 mg, 74%) as a slightlyyellow solid. LCMS (m/z: m+1): 386.4. A mixture of 37 (9.5 g, 73.3 mmol), 4-fluorophenylboronic acid (10.3 g, 73.3 mmol), Na2CO3 (15.5 g, 147 mmol), and Pd(PPh3)4 (1.5g) in CH3CN/H2O (2/1, 200 mL) was heated at reflux under N2 for 16 h. After cooling, themixture was diluted with water and extracted with EtOAc twice. The combined organic layerswere washed with brine, dried over Na2SO4, filtered, concentrated and purified by silica gelcolumn chromatography to give 38 (5.1 g, 37%) as a slightly yellow solid. LCMS (m/z: m+1):190.2. A mixture of 38 (5.1 g, 27.0 mmol), 39 (11.2 g, 40.4 mmol), K2CO3 (7.5 g, 54.0 mmol),DMEDA (476 mg, 5.4 mmol) and CuI (1.28 g, 6.7 mmol) in 100 mL of dioxane was stirred at100C under N2 for 24 h. The mixture was filtered, concentrated and purified by columnchromatography to give 40 (1.6 g, 18%) as a slightly yellow solid. LCMS (m/z: m+1): 338.3.To a solution of 40 (1.6 g, 4.74 mmol) in THF/H2O (32/16 mL) was added LiOH (341 mg,14.2 mmol). The reaction was stirred at room temperature overnight and then concentrated. Tothe residue, water was added and then acidified to pH 4 with aqueous KHSO4. The precipitatewas filtered and washed with water and EtOAc. The cake was collected and dried to give 41(1.3 g, 85%) as an off-white solid. LCMS (m/z: m+1): 324.1. A mixture of 36 (130 mg, 0.34mmol), 41 (109 mg, 0.34 mmol), HATU (257 mg, 0.68 mmol) and DIEA (218 mg, 1.69 mmol)in DMF (2 mL) was heated at 70C overnight. After cooling, the reaction mixture was directlypurified by reverse prep-HPLC and then silica gel prep-TLC to give 42 (33 mg, 14%) as aslightly yellow solid. LCMS (m/z: m+1): 691.3. To a solution of 42 (33 mg, 0.048 mmol) inCH2Cl2 (2 mL) was added TFA (1 mL) and the reaction was stirred at room temperature for 4h before being concentrated under reduced pressure. The residue was treated with water,basified with 0.5 N NaOH and extracted with CH2Cl2/MeOH (15/1) 3 times. The combinedorganic layers were dried over Na2SO4, filtered, concentrated and purified by reverse prep-HPLC to give 2a (14 mg, 50%) as an off-white solid.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 90347-66-3, its application will become more common.
Reference:
Article; Bonnar, James; Dixon, Ian; Evison, Benny J.; Kelly, Graham E.; Kumar, Sanjay; Lambert, Gilles; Nativel, Brice; Palmer, James T.; Parmar, Jasneet; Rathi, Anuj Kumar; Suchowerska, Alexandra K.; Tang, Wei; Teng, Yanfen; Treutlein, Herbert; Wang, Jie; Xu, Yanfeng; Zeng, Jun; Zhu, Qing; Chemello, Kevin; Bioorganic and medicinal chemistry; vol. 28; 6; (2020);,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com