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Formic Acid → cis-(3aRS,9bRS)-7-[2-(3-{pyrrolidin-1-yl}propyl)-4-fluorobenzenesulfonylamino]-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylic acid

HRID 927853
Notes
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Reaction equation

HRID 927853 reaction equation
[OH-].[Li+].[N:3]1([CH2:8][CH2:9][CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=2[S:18]([NH:21][C:22]2[C:31]([C:32]([O:34]C)=[O:33])=[C:30]3[C:25]([C@H:26]4[CH2:38][CH2:37][O:36][C@H:27]4[CH2:28][O:29]3)=[CH:24][CH:23]=2)(=[O:20])=[O:19])[CH2:7][CH2:6][CH2:5][CH2:4]1.C(O)=O>O1CCOCC1.O>[N:3]1([CH2:8][CH2:9][CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=2[S:18]([NH:21][C:22]2[C:31]([C:32]([OH:34])=[O:33])=[C:30]3[C:25]([C@H:26]4[CH2:38][CH2:37][O:36][C@H:27]4[CH2:28][O:29]3)=[CH:24][CH:23]=2)(=[O:20])=[O:19])[CH2:7][CH2:6][CH2:5][CH2:4]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 284Formic AcidHCID 3939Lithium HydroxideHCID 86713241methyl cis-(3aRS,9bRS)-7-[2-(3-{pyrrolidin-1-yl}propyl)-4-fluorobenzenesulfonylamino]-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate2×

Product 1

HCID 86713240cis-(3aRS,9bRS)-7-[2-(3-{pyrrolidin-1-yl}propyl)-4-fluorobenzenesulfonylamino]-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylic acidYield 10.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Lithium hydroxide (0.028 g) was added to a solution of methyl cis-(3aRS,9bRS)-7-[2-(3-{pyrrolidin-1-yl}propyl)-4-fluorobenzenesulfonylamino]-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate (Intermediate 14, 0.06 g) in dioxane (2 mL) and water (1 mL) and the mixture was stirred and heated at 80° C. for 8 hours. After cooling, the mixture was acidified by addition of aqueous formic acid solution (10%) and extracted with DCM. The organic layer was dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica eluting with a mixture of ammonia in methanol (2M) and DCM with a gradient of 1-10%. The isolated solid was triturated with a mixture of ether and cyclohexane (50%) and the solid was collected by filtration. The solid was purified by preparative HPLC (C18) eluting with a mixture of acetonitrile and water, containing 0.1% formic acid, with a gradient of 10-95%. The isolated product was triturated with ether and the solid was collected by filtration to give cis-(3aRS,9bRS)-7-[2-(3-{pyrrolidin-1-yl}propyl)-4-fluorobenzenesulfonylamino]-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylic acid (0.006 g) as a white solid.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with DCM
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica eluting with a mixture of ammonia in methanol (2M) and DCM with a gradient of 1-10%
  7. customThe isolated solid was triturated with a mixture of ether and cyclohexane (50%)
  8. filtrationthe solid was collected by filtration
  9. customThe solid was purified by preparative HPLC (C18)
  10. washeluting with a mixture of acetonitrile and water
  11. additioncontaining 0.1% formic acid
  12. customThe isolated product was triturated with ether
  13. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-42774c228f4f4233a3fb9666b5b279fd
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09290472B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes