Formic Acid → HCID 78078738, compound

HRID 927882Notes

Reaction equation

HRID 927882 reaction equation
[CH2:1]([N:3]1[CH2:6][CH:5]([CH2:7][CH2:8][C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[S:16]([NH:19][C:20]2[C:29]([C:30]([O:32]C)=[O:31])=[C:28]3[C:23]([CH:24]4[CH2:34][CH:25]4[CH2:26][O:27]3)=[CH:22][CH:21]=2)(=[O:18])=[O:17])[CH2:4]1)[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH2:1]([N:3]1[CH2:4][CH:5]([CH2:7][CH2:8][C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[S:16]([NH:19][C:20]2[C:29]([C:30]([OH:32])=[O:31])=[C:28]3[C:23]([CH:24]4[CH2:34][CH:25]4[CH2:26][O:27]3)=[CH:22][CH:21]=2)(=[O:17])=[O:18])[CH2:6]1)[CH3:2]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86713354HCID 86713354, compound2×

Product 1

HCID 78078738HCID 78078738, compoundYield 81.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl (1aRS,7bSR)-5-{2-[2-(1-ethylazetidin-3-yl)ethyl]-4-fluorobenzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (intermediate 183, 0.306 g) and lithium hydroxide monohydrate (0.421 g) in dioxane (7.5 mL) and water (2.5 mL) was irradiated in the microwave at 130° C. for 45 minutes. After cooling, the mixture was diluted with methanol, acidified with formic acid and evaporated in vacuo. The residue was triturated with 20% methanol in DCM, filtered and the filtrate was evaporated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-30%. The resultant solid was triturated with ether and filtered to give (1aRS,7bSR)-5-{2-[2-(1-ethyl-azetidin-3-yl)ethyl]-4-fluorbenzenesulfonylamino}1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.241 g) as a white solid.

Workup

  1. customwas irradiated in the microwave at 130° C. for 45 minutes
  2. temperatureAfter cooling
  3. customevaporated in vacuo
  4. customThe residue was triturated with 20% methanol in DCM
  5. filtrationfiltered
  6. customthe filtrate was evaporated in vacuo
  7. customThe residue was purified by chromatography on silica
  8. washeluting with a mixture of methanol and DCM with a gradient of 0-30%
  9. customThe resultant solid was triturated with ether
  10. filtrationfiltered

Sources & evidence

ORD record
ord-65134541b54446f4838c5be439754f4d
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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