* 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] Chemistry - An Asian Journal, 2013, vol. 8, # 4, p. 705 - 708
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Yield
Reaction Conditions
Operation in experiment
99.9%
Stage #1: at 75℃; for 1 h; Inert atmosphere Stage #2: at 0℃; for 0.5 h;
Thionyl chloride (2.30 ml, 32.30 mmol) and N,N-dimethylformamide (DMF) (0.02 ml, 0.20 mmol) were added to 4-iodobenzoic acid (1.00 g, 4.00 mmol), and then the reaction system was substituted with nitrogen, heated to 75 °C, refluxed, and then stirred for 1 hour. The reaction solution was concentrated under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (5 ml), and then a potassium tert-butoxide 1M solution in THF (4.5 ml) was slowly added at a sub-zero temperature, and stirred for 30 minutes. The reaction solution was concentrated under reduced pressure, and the obtained residue was diluted with ethyl acetate and washed with water and brine. An organic solvent layer was collected, dehydrated with anhydrous magnesium sulfate (MgSO4), filtered, and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (Hex:EA=9:1), thereby obtaining 2-(trimethylsilyl)ethyl 4-iodobenzoate (14.00 g, 99.9percent yield). 1H NMR (CDCl3, 400 MHz) δ 7.77 (2H, d, J = 7.5 Hz, aromatic), 7.69 (2H, d, J = 8.0 Hz, aromatic), 1.59 (9H, s, (CH3)3).
To a suspension of 4-iodobenzoic acid (2.00 g, 8.06 mmol) in toluene (16 mL)Thionyl chloride (4 mL) was added at room temperature, and the mixture was stirred under heating reflux for 2 hours.After returning the reaction solution to room temperature,By concentration under reduced pressure,A crude product of 4-iodobenzoyl chloride was obtained.Tert-Butyl alcohol (7.71 mL, 80.6 mmol) and 4- (dimethylamino) pyridine (99 mg, 0.806 mmol) were added at room temperature to a solution of crude 4-iodobenzoyl chloride in pyridine (16 mL)Followed by stirring at 90 ° C. for 28 hours.To the reaction solution was added a saturated aqueous sodium hydrogen carbonate solution at 0 ° C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The resulting crude product was purified by column chromatography (hexane: ethyl acetate = 50: 1) to obtain a colorless oil of tert-butyl 4-iodobenzoate (2.45 g, yield: quantitative) .
Reference：
[1] Patent: JP2015/848, 2015, A, . Location in patent: Paragraph 0215-0217
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Reference：
[1] Journal of Organic Chemistry, 1995, vol. 60, # 24, p. 7947 - 7952
[2] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 7952 - 7966
[3] Patent: US2001/44535, 2001, A1,
In toluene; at 20 - 70℃; for 5.5h;Molecular sieve;
4-lodobenzoic acid (10 g, 40.3 mmol) was dissolved in dry toluene (100 ml, dried over mol. sieves). The solution was heated to 70 C under a flow of nitrogen. A solution of lambda/,lambda/-dimethylformamide di-tert-butyl acetal (24.6 g, 121 mmol) in toluene (25 mL) was added over ca. 30 min. The reaction was mixed for 16 h. At some point the heating unit failed, so the reaction cooled from 70 C to rt. The solution was heated to 70 C for and mixed for 5 h. The sample was concentrated under vacuum, and AcOEt (400 ml) was added. The solution was then washed with 1 :1 sat. NaHCO3/water (150 ml), and sat. NaHCO3, water and sat. NaCI (75 mL each). The organic phase was dried (MgSO4) and concentrated under vacuum to yield light brown oil. HPLC-MS m/z: 327 (M+23).1H-NMR (CDCI3, 400 MHz) delta 7.77 (d, 2H), 7.69 (d, 2H), 1.58 (s, 9H).
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 18 - 25℃; for 18h;
A mixture of 1 ,1-dimethylethyl 4-iodobenzoate (1.1 g, 3.62 mmol, e.g. which can be preparable e.g. according to E.C.Taylor, J. Org. Chem., 1995, 60(24), 7947), 3-butyn-1- ol (0.36 ml, 4.70 mmol, 1.3 equivalents), bis(triphenylphosphine)palladium(ll)dichloride [(PPh3)2PdCI2] (0.13 g ,018 mmol, 5 mol%) and copper(l)iodide (0.014 g, 0.07 mmol, 2 mol%) in triethylamine (5 ml) was stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane (50 ml) and washed with water (50 ml). The organic phase was collected by passing through a hydrophobic frit and evaporated to give a dark brown oil (1.3 g). This was purified by flash chromatography on silica gel (100 g silica cartridge, FlashMaster II), eluting with a gradient of 0 to 100% ethyl acetate in <n="200"/>cyclohexane over 20 minutes. Fractions containing product (obtained from 4:1 cyclohexane : ethyl acetate eluant) were pooled and evaporated to dryness to give the title compound as a brown gummy oil (0.9 g). 1 H NMR (400 MHz, chloroform-d) delta (delta) ppm 1.60 (9H, s), 1.85 (1H, t, J=6.27Hz ), 2.73 (2H, t, J=6.27Hz), 3.85 (2H, q, J=6.27Hz), 7.45 (2H1 d, J=8.53Hz), 7.92 (2H, d, J=8.53Hz).
4-Iodo-t-butyl benzoate (6.98 g, 22.9 mmol) was dissolved in dry THF (45 ml) and cooled to -20 C. with an isopropanol/dry ice bath. Freshly prepared isopropyl magnesium bromide (1.0 M solution in THF, 25 ml, 25 mmol) was added to this solution dropwise. (Johnson, E. C. B.; Kent, S. B. H. J. Am. Chem. Soc. 2006, 128, 6640-6646.) After being stirred for 1.5 h at -20 C., the reaction mixture containing Grignard reagent 4 was added dropwise slowly to a cooled solution of chloromethylphosphonic dichloride (1.57 g, 11.5 mmol) in THF (45 ml) at -20 C. The resulting solution was allowed to warm to room temperature overnight. After the solution was quenched with 2 mL of water, the solvent was removed under reduced pressure. The resulting oil was dissolved in CH2Cl2, and this solution was washed with brine. The combined organic extracts were dried over anhydrous MgSO4(s) and filtered, and the filtrate was concentrated to yield an orange oil that was purified by flash chromatography (silica gel, 2%/v MeOH in CH2Cl2) to give phosphine oxide 5 as a white solid in 3% yield. 1H MR (CDCl3, 400 MHz) delta 8.15-8.11 (m, 4H), 7.92-7.85 (m, 4H), 4.12 (d, J) 6.7 Hz, 2H), 1.61 (s, 18H) ppm; 13C NMR CDCl3, 125 MHz) delta 164.71, 136.20, 133.09, 131.71 (d, J) 10.8 Hz), 29.79 (d, J) 13.2 Hz), 82.31, 37.48 (d, J) 74.4 Hz), 28.33 ppm; 31P NMR (CDCl3, 161 MHz) delta 27.88 ppm; MS (ESI) m/z 473.1273 MNa+[C23H28ClO5PNa+]) 473.1261).
(S)-2-((S)-3-{4-[5-((S)-2-Amino-2-methoxycarbonyl-ethyl)-2-hydroxy-phenoxy]-phenyl}-2-tert-butoxycarbonylamino-propionylamino)-3-(4-hydroxy-phenyl)-propionic acid[ No CAS ]
(S)-2-((S)-3-{4-[5-((S)-2-Amino-2-methoxycarbonyl-ethyl)-2-hydroxy-phenoxy]-phenyl}-2-tert-butoxycarbonylamino-propionylamino)-3-(4-hydroxy-phenyl)-propionic acid pentafluorophenyl ester[ No CAS ]
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