Formic Acid → HCID 78078711, compound

HRID 927880Notes

Reaction equation

HRID 927880 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[S:17]([NH:20][C:21]2[C:30]([C:31]([O:33]C)=[O:32])=[C:29]3[C:24]([CH:25]4[CH2:35][CH:26]4[CH2:27][O:28]3)=[CH:23][CH:22]=2)(=[O:19])=[O:18])[C:5](=[O:36])[CH2:4]1)[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[S:17]([NH:20][C:21]2[C:30]([C:31]([OH:33])=[O:32])=[C:29]3[C:24]([CH:25]4[CH2:35][CH:26]4[CH2:27][O:28]3)=[CH:23][CH:22]=2)(=[O:18])=[O:19])[C:5](=[O:36])[CH2:4]1)[CH3:2]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 77979772HCID 77979772, compound2×

Product 1

HCID 78078711HCID 78078711, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl (1aRS,7bSR)-5-[2-(4-ethyl-2-oxopiperazin-1-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 173, 0.28 g) and lithium hydroxide monohydrate (0.126 g) in dioxane (9 mL) and water (3 mL) was irradiated in the microwave at 130° C. for 30 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 0-20%. The resultant solid was triturated with ether and filtered to give (1aRS,7bSR)-5-[2-(4-ethyl-2-oxo-piperazin-1-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid (0.176 g) as a white solid.

Workup

  1. customwas irradiated in the microwave at 130° C. for 30 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 0-20%
  9. customThe resultant solid was triturated with ether
  10. filtrationfiltered

Sources & evidence

ORD record
ord-4626ec4c79a64f4f9efa44506fea1481
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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