Formic Acid → (1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927855Notes

Reaction equation

HRID 927855 reaction equation
[CH2:1]([N:3]([CH2:33][CH3:34])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:27]([C:28]([O:30]C)=[O:29])=[C:26]2[C:21]([CH:22]3[CH2:32][CH:23]3[CH2:24][O:25]2)=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O.C(O)C>O1CCOCC1.O.C1(C)C=CC=CC=1>[CH2:33]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:27]([C:28]([OH:30])=[O:29])=[C:26]2[C:21]([CH:22]3[CH2:32][CH:23]3[CH2:24][O:25]2)=[CH:20][CH:19]=1)(=[O:15])=[O:16])[CH3:34]

Participants

8

Reactant 4

HCID 284Formic AcidHCID 702EthanolHCID 168937Lithium hydroxide, monohydrateHCID 86713244Methyl (1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 74762981(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acidYield 36.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl (1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 40, 0.185 g) and lithium hydroxide monohydrate (0.159 g) were suspended in dioxane (4 mL) and water (1 mL). The reaction mixture was irradiated in the microwave at 135° C. for 30 minutes. After cooling, the mixture was acidified to pH4 with formic acid, then ethanol and toluene were added and the mixture concentrated in vacuo. The residue was triturated with a mixture of methanol and DCM (10%) and the solid was filtered off and washed with a mixture of methanol and DCM. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-8%. The resultant product was triturated with ethyl acetate and dried in vacuo at 50° C. to give (1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.066 g) as a white solid.

Workup

  1. customThe reaction mixture was irradiated in the microwave at 135° C. for 30 minutes
  2. temperatureAfter cooling
  3. concentrationthe mixture concentrated in vacuo
  4. customThe residue was triturated with a mixture of methanol and DCM (10%)
  5. filtrationthe solid was filtered off
  6. washwashed with a mixture of methanol and DCM
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of methanol and DCM with a gradient of 0-8%
  10. customThe resultant product was triturated with ethyl acetate
  11. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-42f9052d878a45f5a5a97d49ce9e64c0
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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