Acetic Anhydride → 6-[acetoxy-(4H,10H-pyrazolo[-5,1-c][1,4]benzoxazepine-8-yl)-methyl]-6-bromo-7oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

HRID 1744945Notes

Reaction equation

HRID 1744945 reaction equation
[N:1]1[N:10]2[C:4]([CH2:5][O:6][C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[CH2:9]2)=[CH:3][C:2]=1C=O.[Mg+2].[Br-].[Br-].[N+:20]([C:23]1[CH:41]=[CH:40][C:26]([CH2:27][O:28][C:29]([C:31]2[N:32]3[CH:35]([S:36][CH:37]=2)[CH:34]([Br:38])[C:33]3=[O:39])=[O:30])=[CH:25][CH:24]=1)([O-:22])=[O:21].CCN(CC)CC.[CH3:49][C:50]([O:52][C:53](C)=O)=[O:51]>C(#N)C.C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[N+:20]([C:23]1[CH:41]=[CH:40][C:26]([CH2:27][O:28][C:29]([C:31]2[N:32]3[CH:35]([S:36][CH:37]=2)[C:34]([CH:53]([O:52][C:50](=[O:51])[CH3:49])[C:12]2[CH:13]=[CH:14][C:7]4[O:6][CH2:5][C:4]5=[CH:3][CH:2]=[N:1][N:10]5[CH2:9][C:8]=4[CH:11]=2)([Br:38])[C:33]3=[O:39])=[O:30])=[CH:25][CH:24]=1)([O-:22])=[O:21]

Participants

10

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 82241Magnesium BromideHCID 222244824H,10H-pyrazolo[5,1-c][1,4]benzoxazepine-2-carbaldehydeHCID 684433356-Bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

Product 1

HCID 684445336-[acetoxy-(4H,10H-pyrazolo[-5,1-c][1,4]benzoxazepine-8-yl)-methyl]-6-bromo-7oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl esterYield 54%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

4H,10H-pyrazolo[5,1-c][1,4]benzoxazepine-2-carbaldehyde (0.19 g, 0.887 mmol) in acetonitrile (14 ml) was added to MgBr2 (0.49 g, 2.66 mmol) under N2. After 25 minutes 6-Bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (0.342 g, 0.888 mmol.) in THF (14 ml) was added. After 15 minutes the reaction was cooled to −20° C. Ten minutes later added Et3N (3eq) and placed reaction in the dark. After 6.5 hours added Ac2O (0.42 ml, 4.45 mmol) and DMAP (0.011 g, 0.0900 mmol). Warmed to 0° C. and placed in freezer overnight. Reaction solution was concentrated and resulting residue was taken up in EtOAc. Washed with 5% citric acid(aq) and saturated NaHCO3(aq). Further washed with water and brine. Dried organics over sodium sulfate and filtered and concentrated. Purified with silica gel prep plates and 1:2 EtOAc/Hexane. Obtained the condensation product (yellow gum/solid). Yield: 0.31 g, 54% yield.

Workup

  1. customreaction in the dark
  2. temperatureWarmed to 0° C.
  3. customReaction solution
  4. concentrationwas concentrated
  5. customresulting residue
  6. washWashed with 5% citric acid(aq) and saturated NaHCO3(aq)
  7. washFurther washed with water and brine
  8. filtrationDried organics over sodium sulfate and filtered
  9. concentrationconcentrated
  10. customPurified with silica gel prep plates and 1:2 EtOAc/Hexane
  11. customObtained the condensation product (yellow gum/solid)

Sources & evidence

ORD record
ord-262ea64b9f994f5094c09bbf7e838d91
Source dataset
uspto-grants-2006_03
Patent number
US07018997B2

Reaction notes

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