Acetic Acid → methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 927990Notes

Reaction equation

HRID 927990 reaction equation
[CH3:1][O:2][C:3]([N:5]([C:19]1[C:28]([C:29]([O:31][CH3:32])=[O:30])=[C:27]2[C:22]([CH:23]3[CH2:33][CH:24]3[CH2:25][O:26]2)=[CH:21][CH:20]=1)[S:6]([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[N+:16]([O-])=O)(=[O:8])=[O:7])=[O:4].C(O)(=O)C>C(O)C.[Zn]>[CH3:1][O:2][C:3]([N:5]([C:19]1[C:28]([C:29]([O:31][CH3:32])=[O:30])=[C:27]2[C:22]([CH:23]3[CH2:33][CH:24]3[CH2:25][O:26]2)=[CH:21][CH:20]=1)[S:6]([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[NH2:16])(=[O:7])=[O:8])=[O:4]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 86713324methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(4-fluoro-2-nitrobenzene-sulfonyl)amino]-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 86713323methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 702EthanolSolvent

Procedure

A mixture of methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(4-fluoro-2-nitrobenzene-sulfonyl)amino]-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate (Intermediate 111, 0.2 g), zinc (0.54 g) and acetic acid (0.5 g) in ethanol (20 mL) was stirred and heated at reflux for 1 hour. After cooling, the solid was filtered off and the filtrate was evaporated to dryness. The residue was treated with saturated aqueous sodium bicarbonate and extracted with ethyl acetate, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and petroleum ether with a gradient of 30-50% to give methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.15 g) as a white solid.

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hour
  3. temperatureAfter cooling
  4. filtrationthe solid was filtered off
  5. customthe filtrate was evaporated to dryness
  6. additionThe residue was treated with saturated aqueous sodium bicarbonate
  7. extractionextracted with ethyl acetate
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customThe filtrate was evaporated to dryness
  11. customthe residue was purified by chromatography on silica
  12. washeluting with a mixture of ethyl acetate and petroleum ether with a gradient of 30-50%

Sources & evidence

ORD record
ord-3274b17c794d4592ba07e9833e17a138
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

Loading…