Acetic Anhydride → 4-nitrobenzyl (5R)-6-[(acetyloxy)(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 2216626Notes

Reaction equation

HRID 2216626 reaction equation
[Mg+2].[Br-].[Br-].[N:4]1[N:12]2[C:7]([CH2:8][O:9][CH2:10][CH2:11]2)=[CH:6][C:5]=1[CH:13]=[O:14].[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].C(N(CC)CC)C.[C:44](OC(=O)C)(=[O:46])[CH3:45]>C(#N)C.C1COCC1>[C:44]([O:14][CH:13]([C:5]1[CH:6]=[C:7]2[CH2:8][O:9][CH2:10][CH2:11][N:12]2[N:4]=1)[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:46])[CH3:45]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 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 118454226,7-dihydro-4H-pyrazolo(5,1-c)(1,4)oxazine-2-carbaldehyde

Product 1

HCID 118472844-nitrobenzyl (5R)-6-[(acetyloxy)(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 88.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of MgBr2 (0.94 g, 5.1 mmol) in acetonitrile (25 ml) under nitrogen was added 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carbaldehyde (0.26 g, 1.7 mmol) at room temperature with stirring. A solution of (5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl ester (0.58 g, 1.5 mmol) in THF (25 ml) was then added, and the mixture was cooled to −20° C. Triethylamine (0.71 ml, 5.1 mmol) was introduced, and the mixture was stirred at −20° C. in the dark for 5 hr. It was then treated with acetic anhydride (0.6 ml, 6.0 mmol), and 4-N,N-dimethylaminopyridine (24 mg, 0.2 mmol), and kept at 0° C. for 18 hr. The mixture was concentrated and the residue was dissolved in ethyl acetate. The ethyl acetate solution was washed with 5% citric acid, saturated sodium bicarbonate solution, and brine, dried over anhydrous sodium sulfate, and evaporated. The crude material was chromatographed with silica gel (EtOAc-CH2Cl2/1:5) to give 0.77 g of a white foam; MS (ESI) m/z 578.9 (M+H).

Workup

  1. stirringthe mixture was stirred at −20° C. in the dark for 5 hr
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washThe ethyl acetate solution was washed with 5% citric acid, saturated sodium bicarbonate solution, and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customThe crude material was chromatographed with silica gel (EtOAc-CH2Cl2/1:5)

Sources & evidence

ORD record
ord-dd220414386d4935b8cd1635b1533ae8
Source dataset
uspto-grants-2006_09
Patent number
US07112582B2

Reaction notes

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