Formic Acid → HCID 71006958, compound

HRID 927890Notes

Reaction equation

HRID 927890 reaction equation
[CH2:1]([N:3]([CH2:38][CH3:39])[CH2:4]/[C:5](/[CH3:37])=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([N:17]([C:22]1[C:31]([C:32]([O:34]C)=[O:33])=[C:30]2[C:25]([CH:26]3[CH2:36][CH:27]3[CH2:28][O:29]2)=[CH:24][CH:23]=1)C(OC)=O)(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH2:38]([N:3]([CH2:1][CH3:2])[CH2:4]/[C:5](/[CH3:37])=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:22]1[C:31]([C:32]([OH:34])=[O:33])=[C:30]2[C:25]([CH:26]3[CH2:36][CH:27]3[CH2:28][O:29]2)=[CH:24][CH:23]=1)(=[O:15])=[O:16])[CH3:39]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86713271HCID 86713271, compound2×

Product 1

HCID 71006958HCID 71006958, compoundYield 87.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl (1aRS,7bSR)-5-[N-[2-((Z)-3-diethylamino-2-methylprop-1-enyl)-4-fluorobenzenesulfonyl]-N-methoxycarbonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 200, 0.264 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 40 minutes. After cooling, the mixture was diluted with methanol, acidified with formic acid and evaporated in vacuo then azeotroped with a mixture of ethanol and toluene. The residue was triturated with 15% 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 0-40%. The resultant solid was triturated with ether and filtered to give (1aRS,7bSR)-5-[2-((Z)-3-diethylamino-2-methylprop-1-enyl)-4-fluorobenzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.202 g) as a white solid.

Workup

  1. customwas irradiated in the microwave at 130° C. for 40 minutes
  2. temperatureAfter cooling
  3. customevaporated in vacuo
  4. customthen azeotroped with a mixture of ethanol and toluene
  5. customThe residue was triturated with 15% methanol in DCM
  6. filtrationfiltered
  7. customthe filtrate was evaporated in vacuo
  8. customThe residue was purified by chromatography on silica
  9. washeluting with a mixture of methanol and DCM with a gradient of 0-40%
  10. customThe resultant solid was triturated with ether
  11. filtrationfiltered

Sources & evidence

ORD record
ord-cb603c099b174bba9bf0e6b3d21a617c
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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