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Dicyclohexylcarbodiimide → 2-Benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide

HRID 463580
ノート
印刷プレビュー

反応式

HRID 463580 の反応式
[NH2:1][CH:2]1[C:9](=[O:10])[N:8]2[CH:3]1[S:4](=[O:37])[CH2:5][C:6]([CH:27]=[C:28]([S:30][C:31]1[S:35][C:34]([CH3:36])=[N:33][N:32]=1)[CH3:29])=[C:7]2[C:11]([O:13][CH:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].[CH3:38][O:39][N:40]=[C:41]([C:45]1[N:46]=[C:47]([NH:50][C:51]([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[S:48][CH:49]=1)[C:42](O)=[O:43].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH:14]([O:13][C:11]([C:7]1[N:8]2[CH:3]([S:4](=[O:37])[CH2:5][C:6]=1[CH:27]=[C:28]([S:30][C:31]1[S:35][C:34]([CH3:36])=[N:33][N:32]=1)[CH3:29])[CH:2]([NH:1][C:42](=[O:43])[C:41](=[N:40][O:39][CH3:38])[C:45]1[N:46]=[C:47]([NH:50][C:51]([C:58]3[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=3)([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=3)[S:48][CH:49]=1)[C:9]2=[O:10])=[O:12])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=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

5

反応物 3

HCID 10868DicyclohexylcarbodiimideHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 540411297-Amino-2-benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide

生成物 1

HCID 544407692-Benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide
収率 32%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
4 °C

実験手順

A solution of the Z form of 7-amino-2-benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide (3.53 g) in methylene chloride (250 cc) is cooled to 4° C. 2-Methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid (3.28 g) and dicyclohexylcarbodiimide (1.54 g) are added successively. The mixture is stirred for 11/2 hours at 4° C. and then concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is taken up in ethyl acetate (50 cc) and the insoluble material is filtered off. The solution is washed with a saturated aqueous solution of sodium bicarbonate (100 cc) and then with 0.1N hydrochloric acid (100 cc). It is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.2) (80 g) (diameter of the column: 3 cm; height: 64 cm). Elution is carried out with a 35/65 (by volume) ethyl acetate/cyclohexane mixture (300 cc) and then with a 70/30 (by volume) ethyl acetate/cyclohexane mixture (1,200 cc), 60 cc fractions being collected. Fractions 12 to 20 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the Z form of the syn isomer of 2-benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide (2 g) in the form of a hard white foam.

後処理

  1. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C
  2. filtrationthe insoluble material is filtered off
  3. washThe solution is washed with a saturated aqueous solution of sodium bicarbonate (100 cc)
  4. dry with materialIt is dried over sodium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C
  6. customThe residue is chromatographed on a column of Merck silica gel (0.06-0.2) (80 g) (diameter of the column
  7. washElution
  8. customwith a 70/30 (by volume) ethyl acetate/cyclohexane mixture (1,200 cc), 60 cc fractions being collected
  9. concentrationFractions 12 to 20 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C

出典と根拠

ORDレコード
ord-f3e1b9e8f5be4c9cbfbcdea0c335d90c
出典データセット
uspto-grants-1985_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04520193

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート