Formic Acid → HCID 71006862, compound

HRID 927877Notes

Reaction equation

HRID 927877 reaction equation
[CH3:1][N:2]([CH3:34])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[S:15]([NH:18][C:19]1[C:28]([C:29]([O:31]C)=[O:30])=[C:27]2[C:22]([CH:23]3[CH2:33][CH:24]3[CH2:25][O:26]2)=[CH:21][CH:20]=1)(=[O:17])=[O:16].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH3:34][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[S:15]([NH:18][C:19]1[C:28]([C:29]([OH:31])=[O:30])=[C:27]2[C:22]([CH:23]3[CH2:33][CH:24]3[CH2:25][O:26]2)=[CH:21][CH:20]=1)(=[O:17])=[O:16]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86713263HCID 86713263, compound2×

Product 1

HCID 71006862HCID 71006862, compoundYield 45.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl (1aRS,7bSR)-5-[2-(4-dimethylaminobutylamino)-4-fluorobenzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 161, 0.485 g) and lithium hydroxide monohydrate (0.505 g) in dioxane (9 mL) and water (3 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 0-20%. The resultant solid was triturated with ethyl acetate and filtered off to give (1aRS,7bSR)-5-[2-(4-dimethylaminobutylamino)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid (0.215 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 0-20%
  9. customThe resultant solid was triturated with ethyl acetate
  10. filtrationfiltered off

Sources & evidence

ORD record
ord-ad33c45359d84cf08b9af10fb7a89ed1
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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