Method for producing 1-methylcarbapenem production intermediate
An aryl and aralkyl technology, applied in the field of preparation of β-propiolactam derivatives, can solve the problems of expensive, complicated preparation, poor availability of precursor compounds, etc.
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[0105] The invention is illustrated in more detail in the following specific examples, but is not limited to these specific examples. The following abbreviated codes can be used.
[0106] Ts: p-toluenesulfonyl
[0107] TEA: Triethylamine
[0108] DMAP: 4-Dimethylaminopyridine
[0109] Ac: Acetyl
[0110] TBS: tert-butyldimethylsilyl
[0111] DIPEA: Diisopropylethylamine
[0112] In relation to the description of physical properties in the paragraphs set forth below 1 H NMR spectrum ( 1 H NMR) was measured using a JNM-AL 400 nuclear magnetic resonance instrument manufactured by JEOL, Ltd., wherein the chemical shift value is understood as the value when tetramethylsilane (TMS) is specified as δ 0.00 ppm, and the spin coupling constant is expressed as the J value (Hz), spin-coupling splitting patterns are denoted as s for singlets, d for doublets, t for triplets, dd for doublets of doublets, and td for triplets of doublets, respectively And for multiplets denoted m, code...
preparation Embodiment 1
[0114] N-propionyl-N-(2-trifluoromethylphenyl)-p-toluenesulfonamide (Compound 3)
[0115] [Formula 10]
[0116]
[0117] A solution of 32.23 g (0.2 mol) of 2-aminobenzotrifluoride in pyridine (85 mL) was cooled in an ice bath, 38.52 g (0.2 mol) of p-toluenesulfonyl chloride was added thereto and the reaction was carried out at the same temperature for 1 hour . The reaction mixture was poured into water and extracted with ethyl acetate to obtain an organic layer, which was washed successively with dilute hydrochloric acid and saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was recrystallized from ethyl acetate-hexane to obtain 55.79 g (yield: 96.5%) of N-(2-trifluoromethylphenyl)-p-toluenesulfonamide (compound 2 ).
[0118] 1 H NMR (400MHz, CDCl 3 ), δ ppm 2.37(s, 3H), 6.84(br.s, 1H), 7.16-7.23(m, 3H), 7.47-7.53(m, 2H), 7.66(d, J=8.3Hz, 2H), 7.82 (d, J=8.3Hz, 1H).
[0119] In...
Embodiment 1
[0123] N-[(2R)-2-{(3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidine -4-yl}propionyl]-N-(2-trifluoromethylphenyl)-p-toluenesulfonamide (compound 4)
[0124] [Formula 11]
[0125]
[0126]A solution of 22.29 g (60.0 mmol) of N-propionyl-N-(2-trifluoromethylphenyl)-p-toluenesulfonamide (compound 3) in dichloromethane (345 mL) was cooled with an ice bath under a nitrogen atmosphere , 20.98 g (90.0 mmol) of zirconium chloride was added thereto and the mixture was stirred at the same temperature for 30 minutes. 16.5 mL (94.7 mmol) of DIPEA was added to the mixture and the resulting mixture was stirred at the same temperature for 30 minutes, and then 17.25 g (60.0 mmol) of (3S, 4R)-4-acetoxy-3-[(R )-1-(tert-butyldimethylsilyloxy)ethyl]-2-propionolactam. The ice bath was removed and the reaction was allowed to proceed for 1 hour while allowing the temperature to rise to room temperature. At this point the reaction yield (based on HPLC) was 58.4% and the ratio ...
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