Triethylamine → 2-Benzhydryloxycarbonyl-8-oxo-3-[2-(pyrid-3-yl-amino)-thiazol-5-yl]-7-(thien-2-yl-acetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 2413444Notes

Reaction equation

HRID 2413444 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7](Cl)=[O:8].C(N(CC)CC)C.[NH2:17][CH:18]1[C:25](=[O:26])[N:24]2[CH:19]1[S:20][CH2:21][C:22]([C:43]1[S:47][C:46]([NH:48][C:49]3[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=3)=[N:45][CH:44]=1)=[C:23]2[C:27]([O:29][CH:30]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>O1CCCC1>[CH:30]([O:29][C:27]([C:23]1[N:24]2[CH:19]([S:20][CH2:21][C:22]=1[C:43]1[S:47][C:46]([NH:48][C:49]3[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=3)=[N:45][CH:44]=1)[CH:18]([NH:17][C:7](=[O:8])[CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[C:25]2=[O:26])=[O:28])([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1623622-Thiopheneacetyl chlorideHCID 139605317-Amino-2-benzhydryloxycarbonyl-3-[2-(pyrid-3-yl-amino)-thiazol-5-yl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Product 1

HCID 204304032-Benzhydryloxycarbonyl-8-oxo-3-[2-(pyrid-3-yl-amino)-thiazol-5-yl]-7-(thien-2-yl-acetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Thien-2-yl-acetyl chloride (0.88 cc) and triethylamine (0.95 cc) are added successively to a solution, cooled to 5° C., of 7-amino-2-benzhydryloxycarbonyl-8-oxo-3-[2-(pyrid-3-yl-amino)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene (3.85 g) in dry tetrahydrofuran (100 cc), and the mixture is then stirred for 35 minutes at the same temperature. The cooling bath is removed and the mixture is stirred for 1 hour 30 minutes at 23° C. The reaction mixture is poured onto a mixture (50:50 by volume) (400 cc) of ethyl acetate and saturated sodium bicarbonate solution. The phases are allowed to separate and the organic phase is washed successively with distilled water (200 cc) and a saturated sodium chloride solution (200 cc). It is dried over anhydrous magnesium sulphate and filtered, and the filtrate is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is chromatographed on a column (height: 30 cm, diameter: 3 cm) of silica gel (0.6-0.04 mm), elution being carried out with ethyl acetate (2 liters) and 100 cc fractions being collected. Fractions 5 to 8, containing the pure product, are combined and concentrated under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give 2-benzhydryloxycarbonyl-8-oxo-3-[2-(pyrid-3-yl-amino)-thiazol-5-yl]-7-(thien-2-yl-acetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene (1.3 g) in the form of a yellow froth.

Workup

  1. customThe cooling bath is removed
  2. stirringthe mixture is stirred for 1 hour 30 minutes at 23° C
  3. additionThe reaction mixture is poured onto a mixture (50:50 by volume) (400 cc) of ethyl acetate and saturated sodium bicarbonate solution
  4. customto separate
  5. washthe organic phase is washed successively with distilled water (200 cc)
  6. dry with materialIt is dried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  9. customThe residue is chromatographed on a column (height: 30 cm, diameter: 3 cm) of silica gel (0.6-0.04 mm), elution
  10. custombeing collected
  11. additionFractions 5 to 8, containing the pure product
  12. concentrationconcentrated under reduced pressure (30 mm Hg; 4 kPa) at 30° C.

Sources & evidence

ORD record
ord-75d070e319c74d7f820208a209fb69e4
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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