Acetic Anhydride → (5R,6RS)-6-[(RS)-Acetoxyimidazo[1,2-a]quinolin-2-ylmethyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid 4-nitrobenzyl Ester

HRID 638845Notes

Reaction equation

HRID 638845 reaction equation
[CH:1]1[N:5]2[C:6]3[C:11]([CH:12]=[CH:13][C:4]2=[N:3][C:2]=1[CH:14]=[O:15])=[CH:10][CH:9]=[CH:8][CH:7]=3.[N+:16]([C:19]1[CH:37]=[CH:36][C:22]([CH2:23][O:24][C:25]([C:27]2[N:28]3[C@H:31]([S:32][CH:33]=2)[C@@H:30]([Br:34])[C:29]3=[O:35])=[O:26])=[CH:21][CH:20]=1)([O-:18])=[O:17].[Mg+2].[Br-].[Br-].[C:41](OC(=O)C)(=[O:43])[CH3:42]>C(OCC)(=O)C.CCN(CC)CC.C(#N)C.C1COCC1>[N+:16]([C:19]1[CH:37]=[CH:36][C:22]([CH2:23][O:24][C:25]([C:27]2[N:28]3[C@H:31]([S:32][CH:33]=2)[C:30]([CH:14]([O:15][C:41](=[O:43])[CH3:42])[C:2]2[N:3]=[C:4]4[CH:13]=[CH:12][C:11]5[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=5)[N:5]4[CH:1]=2)([Br:34])[C:29]3=[O:35])=[O:26])=[CH:21][CH:20]=1)([O-:18])=[O:17]

Participants

9

Reactant 4

HCID 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 13770453Imidazo[1,2-a]quinoline-2-carbaldehyde

Product 1

HCID 68444534(5R,6RS)-6-[(RS)-Acetoxyimidazo[1,2-a]quinolin-2-ylmethyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid 4-nitrobenzyl Ester

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

Imidazo[1,2-a]quinoline-2-carbaldehyde (1.09 g) and a dry THF solution (75.5 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 (2.22 g) were added successively to a dry acetonitrile (75.5 mL) solution of anhydrous MgBr2 (2.5 g) under an argon atmosphere at room temperature. After cooling to −20° C., Et3N (1.85 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 a silica gel column, then the column was eluted with CHCl3-acetone (1/0˜95/5). Collected fractions were concentrated under reduced pressure followed by recrystallization from CHCl3-Et2O to give the title compound as one isomer. (pale yellow crystals, yield: 1.3 g, 38%).

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 15 h at 0° C
  3. washwashed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered through a pad of Celite
  6. washThe pad was washed with ethyl acetate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. washthe column was eluted with CHCl3-acetone (1/0˜95/5)
  9. concentrationCollected fractions were concentrated under reduced pressure
  10. customfollowed by recrystallization from CHCl3-Et2O

Sources & evidence

ORD record
ord-dd465f030a694093b7bf7ac936dc066b
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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