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Lithium Hydroxide → (1aR,7bS)-5-{2-[2-((R)-1-ethylpyrrolidin-2-yl)ethyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927895
Notes
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Reaction equation

HRID 927895 reaction equation
[OH-].[Li+].[CH2:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[CH2:10][CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[S:19]([NH:22][C:23]1[C:32]([C:33]([O:35]C)=[O:34])=[C:31]2[C:26]([C@H:27]3[CH2:37][C@H:28]3[CH2:29][O:30]2)=[CH:25][CH:24]=1)(=[O:21])=[O:20])[CH3:4]>O1CCOCC1.O>[CH2:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[CH2:10][CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[S:19]([NH:22][C:23]1[C:32]([C:33]([OH:35])=[O:34])=[C:31]2[C:26]([C@H:27]3[CH2:37][C@H:28]3[CH2:29][O:30]2)=[CH:25][CH:24]=1)(=[O:20])=[O:21])[CH3:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 71006893Methyl (1aR,7bS)-5-{2-[2-((R)-1-ethylpyrrolidin-2-yl)ethyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 71006925(1aR,7bS)-5-{2-[2-((R)-1-ethylpyrrolidin-2-yl)ethyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acidYield 43.5%

Reagents, catalysts & solvents 2

HCID 962
Water
Solvent
HCID 312751,4-DioxaneSolvent

Procedure

Lithium hydroxide (0.22 g) was added to a solution of methyl (1aR,7bS)-5-{2-[2-((R)-1-ethyl-pyrrolidin-2-yl)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 229, 0.26 g) in a mixture of dioxane (12 mL) and water (4 mL) and the mixture was irradiated in a microwave at 150° C. for 20 minutes. After cooling, the mixture was evaporated to dryness and the residue was acidified by addition of 10% aqueous citric acid (3 mL) and then extracted with DCM. The organic layer was dried (MgSO4) and filtered and the filtrate was evaporated to dryness. The residue was purified by preparative HPLC (C18) eluting with a mixture of acetonitrile and water, containing 0.1% formic acid, with a gradient of 25-35% to give (1aR,7bS)-5-{2-[2-((R)-1-ethylpyrrolidin-2-yl)ethyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.11 g) as a white solid.

Workup

  1. customthe mixture was irradiated in a microwave at 150° C. for 20 minutes
  2. temperatureAfter cooling
  3. customthe mixture was evaporated to dryness
  4. additionthe residue was acidified by addition of 10% aqueous citric acid (3 mL)
  5. extractionextracted with DCM
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. customthe filtrate was evaporated to dryness
  9. customThe residue was purified by preparative HPLC (C18)
  10. washeluting with a mixture of acetonitrile and water
  11. additioncontaining 0.1% formic acid

Sources & evidence

ORD record
ord-01c3867bc00c49e69659912adc91b00d
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09290472B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes