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CAS No. : | 1850-14-2 | MDL No. : | MFCD00008473 |
Formula : | C5H12O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AHJWSRRHTXRLAQ-UHFFFAOYSA-N |
M.W : | 136.15 | Pubchem ID : | 74613 |
Synonyms : |
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Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P261-P264-P271-P280-P303+P361+P353-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501 | UN#: | 1993 |
Hazard Statements: | H225-H315-H319-H335 | Packing Group: | Ⅱ |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With acetic acid; In chloroform; at 60℃; | In accordance with the invention, substituted 2-aminobenzoxazoles can be prepared in one pot using commercially available tetramethyl orthocarbonate (2 eq, Aldrich), an amine (2 eq), and an optionally substituted 2-aminophenol (1 eq). The reaction maybe carried out in the presence of acetic acid (4 eq) in chloroform at 60C (using a sealed tube for volatile amines). Tetramethyl orthocarbonate can be successfully replaced by its tetraethyl analogue in this reaction. Other useful solvents for the reaction include methanol, ethanol, isopropyl alcohol, acetonitrile, tetrahydrofuran, ethyl acetate, toluene, and combinations thereof.The mild reaction conditions permit the reaction to be applied to compounds with sensitive functional groups, for example, esters. The reaction is clean, providing virtually spot-to-spot conversion from an aminophenol to a 2-methoxybenzoxazole to a 2-aminobenzoxazole. The work-up and purification is straightforward and easy; in many cases, a simple re-crystallization may be sufficient for purification of final compounds. The reaction is versatile, as is demonstrated by the variety of amine reactants listed in TABLE 1. As shown by the structures included in TABLE 2, electron donating and withdrawing substituents on the 2-aminophenol are also well tolerated. The reaction by-products are methanol and, optionally, acetic acid. A simplified work-up may only involve concentration under reduced pressure, which makes the reaction particularly amenable to large-scale production. The reaction can be carried out in a variety of solvents, including methanol, acetonitrile, tetrahydrofuran, ethyl acetate, and toluene. Optionally, the solvent may include an acid such as acetic acid. However the reaction proceeds in good yield in chloroform without acetic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; at 100℃; for 1.5h; | A solution of 5-bromo-N*2*-methylpyridine-2,3-diamine (Stage 67.1.4, 960 mg, 4 75 mmo.) and tetramethyl orthocarbonate (Aki?ch, Buchs, Switzerland, 2 ml, 14 7 mmol) and acetic acid (0 273 ml, 4 75 mmol) was stirred for 90 min at 100 C The reaction mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine The aqueous layer was extracted with EtOAc and the combined organic layers washed with saturated aqueous NaHCO3 and with brine, then dried over Na2SO4, filtered and evaprated The crude product was dry loaded on silica gel and purifted by MPLC (DCM/MeOH 0% - 4%) to g>;ve the title compound as a green solid. (HPLC tR 2.83 mm (Method A), M+H - 242, 244 MS-ES). |