Lithium Hydroxide → cis-(3aRS,9bRS)-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,3a,4,5,9b-hexahydrofuro[2,3-c]quinoline-6-carboxylic acid

HRID 927854Notes

Reaction equation

HRID 927854 reaction equation
[OH-].[Li+].C([N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH:20][S:21]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3/[CH:31]=[CH:32]\[CH2:33][N:34]([CH2:37][CH3:38])[CH2:35][CH3:36])(=[O:23])=[O:22])[C:14]=2[C:16]([O:18]C)=[O:17])[C@H:9]2[CH2:39][CH2:40][O:41][C@H:8]2[CH2:7]1)(=O)C>O1CCOCC1.O>[CH2:37]([N:34]([CH2:35][CH3:36])[CH2:33]/[CH:32]=[CH:31]\[C:25]1[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=1[S:21]([NH:20][C:13]1[C:14]([C:16]([OH:18])=[O:17])=[C:15]2[C:10]([C@H:9]3[CH2:39][CH2:40][O:41][C@H:8]3[CH2:7][NH:6]2)=[CH:11][CH:12]=1)(=[O:23])=[O:22])[CH3:38]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86713243methyl cis-(3aRS,9bRS)-5-acetyl-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,3a,4,5,9b-hexahydrofuro[2,3-c]quinoline-6-carboxylate2×

Product 1

HCID 86713242cis-(3aRS,9bRS)-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,3a,4,5,9b-hexahydrofuro[2,3-c]quinoline-6-carboxylic acidYield 9.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Lithium hydroxide (0.09 g) was added to a solution of methyl cis-(3aRS,9bRS)-5-acetyl-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,3a,4,5,9b-hexahydrofuro[2,3-c]quinoline-6-carboxylate (Intermediate 27, 0.06 g) in a mixture of dioxane (5 mL) and water (1 mL) and the mixture was stirred and heated at 80° C. overnight. The mixture was then irradiated in the microwave at 150° C. for 30 minutes and then at 180° C. for 30 minutes. After cooling, the mixture was filtered and the filtrate was acidified by addition of formic acid (1 mL) and then evaporated to dryness. The residue was purified by preparative HPLC (C18) eluting with a mixture of acetonitrile and water, containing 0.1% formic acid, with a gradient of 10-98%. The isolated product was dissolved in DCM and evaporated to dryness then dissolved in ether and evaporated to dryness to give cis-(3aRS,9bRS)-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,3a,4,5,9b-hexahydrofuro[2,3-c]quinoline-6-carboxylic acid (0.005 g) as a white solid.

Workup

  1. customThe mixture was then irradiated in the microwave at 150° C. for 30 minutes
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered
  4. additionthe filtrate was acidified by addition of formic acid (1 mL)
  5. customevaporated to dryness
  6. customThe residue was purified by preparative HPLC (C18)
  7. washeluting with a mixture of acetonitrile and water
  8. additioncontaining 0.1% formic acid
  9. dissolutionThe isolated product was dissolved in DCM
  10. customevaporated to dryness
  11. dissolutionthen dissolved in ether
  12. customevaporated to dryness

Sources & evidence

ORD record
ord-297354883a7d4aacab5eb01cb8966de3
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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