Water → (1aRS,7bSR)-5-(2-{[((R)-1-ethylpyrrolidine-2-yl)carbonylamino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid

HRID 927873Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 927873
[CH2:1]([N:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[C:8]([NH: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]([CH:27]3[CH2:37][CH:28]3[CH2:29][O:30]2)=[CH:25][CH:24]=1)(=[O:21])=[O:20])=[O:9])[CH3:2].O.[OH-].[Li+].O>O1CCOCC1>[CH2:1]([N:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[C:8]([NH: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]([CH:27]3[CH2:37][CH:28]3[CH2:29][O:30]2)=[CH:25][CH:24]=1)(=[O:20])=[O:21])=[O:9])[CH3:2]

Komponenten

5

Edukt 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 71006867Methyl (1aRS,7bSR)-5-(2-{[((R)-1-ethylpyrrolidine-2-yl)carbonylamino]-methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Produkt 1

HCID 86713258(1aRS,7bSR)-5-(2-{[((R)-1-ethylpyrrolidine-2-yl)carbonylamino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acidAusbeute 36,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of methyl (1aRS,7bSR)-5-(2-{[((R)-1-ethylpyrrolidine-2-yl)carbonylamino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 146, 0.120 g) and lithium hydroxide monohydrate (0.095 g) was suspended in dioxane (5 mL) and water (1 mL) and the mixture was stirred and heated at 110° C. for 22.5 hours. After cooling, the volatiles were removed in vacuo and the residue was acidified by addition of aqueous citric acid solution (10%) and extracted with DCM. The organic layer was dried (Na2SO4) and filtered and the filtrate was evaporated to dryness. The residue was purified by preparative HPLC (C18) eluting with a mixture of methanol and water, containing 0.1% formic acid, with a gradient of 10-98% to give (1aRS,7bSR)-5-(2-{[((R)-1-ethylpyrrolidine-2-yl)carbonylamino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid (0.043 g) as a white solid.

Aufarbeitung

  1. temperatureAfter cooling
  2. customthe volatiles were removed in vacuo
  3. additionthe residue was acidified by addition of aqueous citric acid solution (10%)
  4. extractionextracted with DCM
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customthe filtrate was evaporated to dryness
  8. customThe residue was purified by preparative HPLC (C18)
  9. washeluting with a mixture of methanol and water
  10. additioncontaining 0.1% formic acid

Quellen und Nachweise

ORD-Eintrag
ord-53b85eb55a6a4dfab177d7b538059a11
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290472B2

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