Sodium Iodide → benzhydryl (6R)-3-[(5,6-dihydroxy-1,3-dihydroisoindol-2-yl)methyl]-5,8-dioxo-7-[[(2Z)-2-propan-2-yloxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 653561ノート

反応式

HRID 653561 の反応式
Cl[CH2:2][C:3]1[CH2:4][S:5](=[O:62])[C@@H:6]2[CH:26]([NH:27][C:28](=[O:60])/[C:29](=[N:55]\[O:56][CH:57]([CH3:59])[CH3:58])/[C:30]3[N:31]=[C:32]([NH:35][C:36]([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[S:33][CH:34]=3)[C:25](=[O:61])[N:7]2[C:8]=1[C:9]([O:11][CH:12]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].[I-].[Na+].Br.[OH:66][C:67]1[CH:68]=[C:69]2[C:73](=[CH:74][C:75]=1[OH:76])[CH2:72][NH:71][CH2:70]2.C(N(CC)CC)C>CC(C)=O>[OH:66][C:67]1[CH:68]=[C:69]2[C:73](=[CH:74][C:75]=1[OH:76])[CH2:72][N:71]([CH2:2][C:3]1[CH2:4][S:5](=[O:62])[C@@H:6]3[CH:26]([NH:27][C:28](=[O:60])/[C:29](=[N:55]\[O:56][CH:57]([CH3:59])[CH3:58])/[C:30]4[N:31]=[C:32]([NH:35][C:36]([C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)[C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[S:33][CH:34]=4)[C:25](=[O:61])[N:7]3[C:8]=1[C:9]([O:11][CH:12]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH2:70]2

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 200743492,3-dihydro-1H-isoindole-5,6-diol hydrobromideHCID 88634111benzhydryl (6R)-3-(chloromethyl)-5,8-dioxo-7-[[(2Z)-2-propan-2-yloxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

生成物 1

HCID 141559957benzhydryl (6R)-3-[(5,6-dihydroxy-1,3-dihydroisoindol-2-yl)methyl]-5,8-dioxo-7-[[(2Z)-2-propan-2-yloxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate収率 78%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

実験手順

2.0 g (2.26 mmol) of Benzhydryl 3-chloromethyl-7-[(Z)-2-isopropoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate 1-oxide was dissolved in 40 ml of acetone, and 750 mg (5 mmol) of sodium iodide was added thereto under cooling with ice. The mixture was stirred for 30 minutes. The reaction solution was concentrated under reduced pressure. To the residue, ethyl acetate and water were added. The organic layer was washed with a sodium metabisulfite aqueous solution and with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The oily residue was dissolved in 10 ml of N,N-dimethylformamide, and 790 mg (3.4 mmol) of 5,6-dihydroxyisoindoline hydrobromide was added thereto, then 0.47 ml (3.38 mmol) of triethylamine was dropwise added at room temperature. The reaction solution was stirred at the same temperature for 2 hours, and then N,N-dimethylformamide was distilled off under reduced pressure. To the residue, chloroform and water were added. The organic layer was washed with water and with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flush column chromatography (5% methanol-chloroform) to obtain 1.74 g (yield: 78%) of the above-identified compound.

後処理

  1. temperatureunder cooling with ice
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additionTo the residue, ethyl acetate and water were added
  4. washThe organic layer was washed with a sodium metabisulfite aqueous solution and with a saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe oily residue was dissolved in 10 ml of N,N-dimethylformamide
  8. stirringThe reaction solution was stirred at the same temperature for 2 hours
  9. distillationN,N-dimethylformamide was distilled off under reduced pressure
  10. additionTo the residue, chloroform and water were added
  11. washThe organic layer was washed with water and with a saturated sodium chloride aqueous solution
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel
  15. customflush column chromatography (5% methanol-chloroform)

出典と根拠

ORDレコード
ord-b48b19b165f14adab6c87020f9b496e9
出典データセット
uspto-grants-1987_06
特許番号
US04677100

反応ノート

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