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Methanesulfonyl chloride → benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)methoxy]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467383
ノート
印刷プレビュー

反応式

HRID 467383 の反応式
Cl.[C:2]([NH:21][C:22]1[S:23][CH:24]=[C:25](/[C:27](=[N:31]/[O:32][CH3:33])/[C:28](O)=[O:29])[N:26]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.[NH2:48][C@@H:49]1[C:80](=[O:81])[N:51]2[C:52]([C:64]([O:66][CH:67]([C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)[C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)=[O:65])=[C:53]([O:56][CH2:57][C:58]3[CH2:62][O:61][C:60](=[O:63])[CH:59]=3)[CH2:54][S:55][C@H:50]12>CN(C)C=O.O.C(OCC)(=O)C.N1C=CC=CC=1>[O:63]=[C:60]1[CH:59]=[C:58]([CH2:57][O:56][C:53]2[CH2:54][S:55][C@@H:50]3[C@H:49]([NH:48][C:28](=[O:29])/[C:27](/[C:25]4[N:26]=[C:22]([NH:21][C:2]([C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=5)([C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=5)[C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=5)[S:23][CH:24]=4)=[N:31]\[O:32][CH3:33])[C:80](=[O:81])[N:51]3[C:52]=2[C:64]([O:66][CH:67]([C:74]2[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=2)[C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)=[O:65])[CH2:62][O:61]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 67908486Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-4-ylmethyloxy)ceph-3-em-4-carboxylate

生成物 1

HCID 88501966
benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)methoxy]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-50 °C

実験手順

A stirred solution of 2-(2-tritylaminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid hydrochloride (300 mg) in dimethylformamide (4 ml) was cooled to -50° C. whilst under an inert atmosphere. N,N-Diisopropylethylamine (218 μl) was added followed by methanesulphonyl chloride (49 μl). The reaction was stirred for 30 min. at -50° C. before treating with pyridine (52 μl) followed by a solution of diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-4-ylmethyloxy)ceph-3-em-4-carboxylate (300 mg) in dimethylformamide (4 ml) and the temperature allowed to rise to 0° C. The reaction was stirred for 15 min. and then poured into ethyl acetate and water. The organic phase was washed with water (two times) and brine before drying over anhydrous magnesium sulphate. Chromatography on silica gel (Keiselgel) eluting with 4:1 ethyl acetate/hexane gave the title compound which was finally isolated as a foam (431 mg). υmax (CH2Cl2) 3400, 1785, 1755, and 1730cm-1 ; δH(CDCl3) 3.34 (2H, s), 4.08 (3H, s), 4.64 (2H, s) 4.73 (2H, bs), 5.11 (1H, d, J 4.5Hz), 5.79 (1H, dd, J 8.24Hz, 4.5Hz), 5.95 (1H, bs) 6.77 (1H, s), 6.90 (1H, s), 6.96 (1H, d, J 8.07Hz), 7.02 (1H, s), and 7.26-7.39 (25H, m). [Mass spectrum: FAB +ve ion (3NOBA/Na+)MH+ 904, MNa+ 926].

後処理

  1. customto rise to 0° C
  2. stirringThe reaction was stirred for 15 min.
  3. washThe organic phase was washed with water (two times) and brine
  4. dry with materialbefore drying over anhydrous magnesium sulphate
  5. washChromatography on silica gel (Keiselgel) eluting with 4:1 ethyl acetate/hexane

出典と根拠

ORDレコード
ord-3a9efdcfefb54507879f5231df179342
出典データセット
uspto-grants-1992_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05158946

反応ノート

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