Lithium hydroxide, monohydrate → (1aRS,7bSR)-5-{2[(Z)-3-(propan-2-yl)aminoprop-1-enyl]-4-fluorobenzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927861Notes

Reaction equation

HRID 927861 reaction equation
[CH3:1][CH:2]([NH:4][CH2:5]/[CH:6]=[CH:7]\[C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[S:15]([NH:18][C:19]1[C:28]([C:29]([O:31]C)=[O:30])=[C:27]2[C:22]([CH:23]3[CH2:33][CH:24]3[CH2:25][O:26]2)=[CH:21][CH:20]=1)(=[O:17])=[O:16])[CH3:3].O.[OH-].[Li+]>O1CCOCC1.O>[CH3:3][CH:2]([NH:4][CH2:5]/[CH:6]=[CH:7]\[C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[S:15]([NH:18][C:19]1[C:28]([C:29]([OH:31])=[O:30])=[C:27]2[C:22]([CH:23]3[CH2:33][CH:24]3[CH2:25][O:26]2)=[CH:21][CH:20]=1)(=[O:17])=[O:16])[CH3:1]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86713251methyl (1aRS,7bSR)-5-{2[(Z)-3-(propan-2-yl)aminoprop-1-enyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 86713250(1aRS,7bSR)-5-{2[(Z)-3-(propan-2-yl)aminoprop-1-enyl]-4-fluorobenzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acidYield 34.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl (1aRS,7bSR)-5-{2[(Z)-3-(propan-2-yl)aminoprop-1-enyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 69, 0.12 g) and lithium hydroxide monohydrate (0.1 g) in a mixture of dioxane (10 mL) and water (5 mL) was stirred and heated at 100° C. overnight. After cooling, the mixture was concentrated under vacuum and the residue was acidified to pH4 with formic acid then extracted with a mixture of ethyl acetate and THF (1:1). The organic phase was dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was dissolved in ethyl acetate (2 mL) and hexane was added (10 mL). The solid was collected by filtration and washed with ether to give (1aRS,7bSR)-5-{2[(Z)-3-(propan-2-yl)aminoprop-1-enyl]-4-fluorobenzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.04 g) as an off white solid.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated under vacuum
  3. extractionthen extracted with a mixture of ethyl acetate and THF (1:1)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness
  7. dissolutionthe residue was dissolved in ethyl acetate (2 mL)
  8. additionhexane was added (10 mL)
  9. filtrationThe solid was collected by filtration
  10. washwashed with ether

Sources & evidence

ORD record
ord-de7d2b389e9a4ba584ca823a0ef95831
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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