Acetic Anhydride → 4-nitrobenzyl (5R)-6-[(acetyloxy)(4-oxo-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 1158878Notes

Reaction equation

HRID 1158878 reaction equation
[Mg+2].[Br-].[Br-].[O:4]=[C:5]1[C:10]2=[CH:11][C:12]([CH:14]=[O:15])=[N:13][N:9]2[CH2:8][CH2:7][O:6]1.[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].C(N(CC)CC)C.[C:45](OC(=O)C)(=[O:47])[CH3:46]>C(#N)C.C1COCC1>[C:45]([O:15][CH:14]([C:12]1[CH:11]=[C:10]2[C:5](=[O:4])[O:6][CH2:7][CH2:8][N:9]2[N:13]=1)[C:30]1([Br:34])[C:29](=[O:35])[N:28]2[C@@H:31]1[S:32][CH:33]=[C:27]2[C:25]([O:24][CH2:23][C:22]1[CH:36]=[CH:37][C:19]([N+:16]([O-:18])=[O:17])=[CH:20][CH:21]=1)=[O:26])(=[O:47])[CH3:46]

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 21941485HCID 21941485, compound

Product 1

HCID 865914314-nitrobenzyl (5R)-6-[(acetyloxy)(4-oxo-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 54.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of MgBr2 (0.46 g, 2.52 mmol) in acetonitrile (13 ml) under nitrogen was added 4-oxo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carbaldehyde (0.14 g, 0.84 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 (0.32 g, 0.84 mmole) in THF (13 ml) was then added, and the mixture was cooled to −20° C. Triethylamine (0.35 ml, 2.52 mmol) was introduced, and the mixture was stirred at −20° C. in the dark for 4 hr. It was then treated with acetic anhydride (0.2 ml, 2.0 mmol), and 4-N,N-dimethylaminopyridine (12 mg, 0.1 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 0.27 g of an off-white solid; mp 107-110° C.; MS m/e 595 (MH+).

Workup

  1. stirringthe mixture was stirred at −20° C. in the dark for 4 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-d2cd1f4ae050439aa696ab03051165df
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

Loading…