Diethyl Ether → 4-nitrobenzyl (5R)-6-[(acetyloxy)(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 638874ノート

反応式

HRID 638874 の反応式
[N:1]1[C:2]([CH:13]=[O:14])=[CH:3][N:4]2[C:8]3[CH2:9][CH2:10][CH2:11][CH2:12][C:7]=3[S:6][C:5]=12.[N+:15]([C:18]1[CH:36]=[CH:35][C:21]([CH2:22][O:23][C:24]([C:26]2[N:27]3[C@H:30]([S:31][CH:32]=2)[C@@H:29]([Br:33])[C:28]3=[O:34])=[O:25])=[CH:20][CH:19]=1)([O-:17])=[O:16].[Mg+2].[Br-].[Br-].[O:40](CC)[CH2:41][CH3:42].C(OC(=O)C)(=O)C>C(OCC)(=O)C.CCN(CC)CC.C(#N)C.C1COCC1>[C:41]([O:14][CH:13]([C:2]1[N:1]=[C:5]2[N:4]([CH:3]=1)[C:8]1[CH2:9][CH2:10][CH2:11][CH2:12][C:7]=1[S:6]2)[C:29]1([Br:33])[C:28](=[O:34])[N:27]2[C@@H:30]1[S:31][CH:32]=[C:26]2[C:24]([O:23][CH2:22][C:21]1[CH:35]=[CH:36][C:18]([N+:15]([O-:17])=[O:16])=[CH:19][CH:20]=1)=[O:25])(=[O:40])[CH3:42]

参加物

10

反応物 5

HCID 3283Diethyl EtherHCID 7918Acetic AnhydrideHCID 82241Magnesium BromideHCID 11280588(5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl esterHCID 222244605,6,7,8-Tetrahydroimidazo[2,1-b][1,3]benzothiazole-2-carbaldehyde

生成物 1

HCID 696085324-nitrobenzyl (5R)-6-[(acetyloxy)(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

試薬・触媒・溶媒 4

HCID 6342Acetonitrile溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-20 °C

実験手順

5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-2-carbaldehyde (412 mg, 2.0 mmol) and the dry THF solution (20 mL) of (5R,6S)-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (770 mg, 2 mmol) were added successively to the dry acetonitrile (15 mL) solution of anhydrous MgBr2:O(Et)2 (1.2 g, 3.0 mmol) under an argon atmosphere at room temperature. After cooling to −20° C., Et3N (2.0 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 2 h at −20° C. and treated with acetic anhydride (1.04 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 15 h at 0° C. The mixture was diluted with ethyl acetate and washed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, and brine. The organic layer was dried (MgSO4) and filtered through a pad of Celite. The pad was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with ethyl acetate:hexane (1:1). Collected fractions were concentrated under reduced pressure and the mixture of diastereomers were taken to the next step. Pale yellow amorphous solid; Yield: 980 mg, 77%; M+H 634.

後処理

  1. customat room temperature
  2. temperatureThe reaction mixture was warmed to 0° C.
  3. stirringstirred for 15 h at 0° C
  4. washwashed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, and brine
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered through a pad of Celite
  7. washThe pad was washed with ethyl acetate
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. washthe column was eluted with ethyl acetate:hexane (1:1)
  10. concentrationCollected fractions were concentrated under reduced pressure
  11. additionthe mixture of diastereomers

出典と根拠

ORDレコード
ord-8dfe3a1493124ec3b4e00880a42978aa
出典データセット
uspto-grants-2010_04
特許番号
US07691842B2

反応ノート

読み込み中…