Formic Acid → HCID 56656281, compound

HRID 1778327Notes

Reaction equation

HRID 1778327 reaction equation
[CH2:1]([N:3]([CH2:35][CH3:36])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:23]([C:24]([O:26]C)=[O:25])=[C:22]2[O:28][CH2:29][C:30]3[CH:31]=[N:32][S:33][C:34]=3[C:21]2=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.C(Cl)Cl>[CH2:35]([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]([NH:17][C:18]1[C:23]([C:24]([OH:26])=[O:25])=[C:22]2[O:28][CH2:29][C:30]3[CH:31]=[N:32][S:33][C:34]=3[C:21]2=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH3:36]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrate2×HCID 68093264HCID 68093264, compound2×

Product 1

HCID 56656281HCID 56656281, compoundYield 47.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-chromeno[3,4-d]isothiazole-6-carboxylate (Intermediate 72, 0.058 g) was dissolved in dioxane (1.5 mL) and water (0.6 mL). Lithium hydroxide monohydrate (0.018 g) was added and the resultant mixture was heated at 85° C., under nitrogen for 3 hours. The mixture was left to cool overnight. A further amount of lithium hydroxide monohydrate (0.010 g) was added and the mixture was heated at 85° C. for a further 1 hour. The mixture was cooled, diluted with DCM and acidified to pH4 with aqueous formic acid (10%), to give an emulsion. The emulsion was concentrated in vacuo to give a gum, which was triturated with a solution of 2M methanol in DCM and the solid was removed by filtration. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM, with a gradient of 0-8%. The resultant product was dissolved in acetonitrile and water and freeze-dried overnight to give 7-[2((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-chromeno[3,4-d]isothiazole-6-carboxylic acid (0.027 g) as a white solid.

Workup

  1. waitThe mixture was left
  2. temperatureto cool overnight
  3. temperatureThe mixture was cooled
  4. customto give an emulsion
  5. concentrationThe emulsion was concentrated in vacuo
  6. customto give a gum, which
  7. customwas triturated with a solution of 2M methanol in DCM
  8. customthe solid was removed by filtration
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of methanol and DCM, with a gradient of 0-8%
  12. dissolutionThe resultant product was dissolved in acetonitrile
  13. dry with materialwater and freeze-dried overnight

Sources & evidence

ORD record
ord-20a3926443ec4f8ba92fb7250f54b299
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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