Lithium Hydroxide → cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 59665Notes

Reaction equation

HRID 59665 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]([CH2:17][C:18]1[C:27]([C:28]([O:30]C)=[O:29])=[C:26]2[C:21]([C@H:22]3[CH2:32][C@H:23]3[CH2:24][O:25]2)=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH3:2].[OH-].[Li+]>O1CCOCC1.O>[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]([CH2:17][C:18]1[C:27]([C:28]([OH:30])=[O:29])=[C:26]2[C:21]([C@H:22]3[CH2:32][C@H:23]3[CH2:24][O:25]2)=[CH:20][CH:19]=1)(=[O:15])=[O:16])[CH3:34]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 131737059methyl cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 71664454cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acidYield 17.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluoro-benzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 1, 0.72 g) and lithium hydroxide (0.622 g) in dioxane (20 mL) and water (5 mL) was stirred and heated at 80° C. for 5 hours. After cooling, the mixture was filtered and the filtrate was concentrated to low volume under vacuum. The aqueous residue was acidified with formic acid to pH 5 and extracted with DCM. The organic layer was dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by reverse phase chromatography using a C-18 5 micron cartridge and eluting with a mixture of methanol and water, with a gradient of 10-98%. The product was repurified by HPLC(C18) eluting with a mixture of acetonitrile and water (containing 0.1% formic acid) to give cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.125 g) as a white solid.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. concentrationthe filtrate was concentrated to low volume under vacuum
  4. extractionextracted with DCM
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customThe filtrate was evaporated to dryness
  8. customthe residue was purified by reverse phase chromatography
  9. washeluting with a mixture of methanol and water, with a gradient of 10-98%
  10. customThe product was repurified by HPLC(C18)
  11. washeluting with a mixture of acetonitrile and water (containing 0.1% formic acid)

Sources & evidence

ORD record
ord-61415556f31444728857e3e2fa13b693
Source dataset
uspto-grants-2016_09
Patent number
US09440943B2

Reaction notes

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