Water → HCID 86713259, compound

HRID 927875Notes

Reaction equation

HRID 927875 reaction equation
[CH2:1]([N:3]([CH2:32][CH3:33])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13]([NH:16][C:17]1[C:26]([C:27]([O:29]C)=[O:28])=[C:25]2[C:20]([CH:21]3[CH2:31][CH:22]3[CH2:23][O:24]2)=[CH:19][CH:18]=1)(=[O:15])=[O:14])[CH3:2].O.[OH-].[Li+].O>O1CCOCC1>[CH2:32]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13]([NH:16][C:17]1[C:26]([C:27]([OH:29])=[O:28])=[C:25]2[C:20]([CH:21]3[CH2:31][CH:22]3[CH2:23][O:24]2)=[CH:19][CH:18]=1)(=[O:15])=[O:14])[CH3:33]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86713260HCID 86713260, compound2×

Product 1

HCID 86713259HCID 86713259, compoundYield 30.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl (1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)benzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 153, 0.495 g) and lithium hydroxide monohydrate (0.442 g) was suspended in dioxane (20 mL) and water (5 mL) and the mixture was stirred and heated at 80° C. for 12.5 hours. After cooling, the volatiles were removed in vacuo and the residue was acidified by addition of aqueous citric acid solution (10%) and extracted with DCM. The organic layer was dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and 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 35-70% to give (1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)benzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.147 g) as a white solid.

Workup

  1. temperatureAfter cooling
  2. customthe volatiles were removed in vacuo
  3. additionthe residue was acidified by addition of aqueous citric acid solution (10%)
  4. extractionextracted with DCM
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customThe filtrate was evaporated to dryness
  8. customthe residue was purified by preparative HPLC (C18)
  9. washeluting with a mixture of acetonitrile and water
  10. additioncontaining 0.1% formic acid

Sources & evidence

ORD record
ord-8699ea35b5004464a101fa6281573baf
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

Loading…