Lithium Hydroxide → (1aRS,7bSR)-5-[2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927865Notes

Reaction equation

HRID 927865 reaction equation
[OH-].[Li+].[CH2:3]([N:5]1[CH2:9][CH2:8][C@@H:7]([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]([CH:26]4[CH2:36][CH:27]4[CH2:28][O:29]3)=[CH:24][CH:23]=2)(=[O:20])=[O:19])[CH2:6]1)[CH3:4]>O1CCOCC1.O>[CH2:3]([N:5]1[CH2:9][CH2:8][C@@H:7]([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]([CH:26]4[CH2:36][CH:27]4[CH2:28][O:29]3)=[CH:24][CH:23]=2)(=[O:19])=[O:20])[CH2:6]1)[CH3:4]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 71006876methyl (1aRS,7bSR)-5-[2-((R)-1-ethyl-pyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate2×

Product 1

HCID 71006980(1aRS,7bSR)-5-[2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acidYield 67.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Lithium hydroxide (0.111 g) was added to a solution of methyl (1aRS,7bSR)-5-[2-((R)-1-ethyl-pyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 95, 0.13 g) in a mixture of dioxane (4 mL) and water (1 mL) and the mixture was stirred and heated at 85° C. overnight. After cooling, the mixture was filtered and the filtrate was acidified by addition of 10% aqueous citric acid (1 mL) and then extracted with DCM. The organic extract was dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with diethyl ether and the solid was collected by filtration to give (1aRS,7bSR)-5-[2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.085 g) as a white solid.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. additionthe filtrate was acidified by addition of 10% aqueous citric acid (1 mL)
  4. extractionextracted with DCM
  5. extractionThe organic extract
  6. dry with materialwas dried (MgSO4)
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness
  9. customthe residue was triturated with diethyl ether
  10. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-28525b6fc6184c3bba972a9accc5f926
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

Loading…