Triethylamine → methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyryl-amino)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate

HRID 927989Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 927989
[Cl:1][CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].[CH3:8][O:9][C:10]([N:12]([C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[NH2:23])(=[O:15])=[O:14])=[O:11].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:8][O:9][C:10]([N:12]([C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[NH:23][C:5](=[O:6])[CH2:4][CH2:3][CH2:2][Cl:1])(=[O:14])=[O:15])=[O:11]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 516892Sodium BicarbonateHCID 86713323methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Produkt 1

HCID 86713322methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyryl-amino)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylateAusbeute 90,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

4-Chlorobutyryl chloride (3.0 g) was added to a stirred, cooled solution of methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 110, 0.135 g) and triethylamine (1.0 g) in THF (10 mL) at 0° C. On completion of the addition, the mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25% to give methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyrylamino)-4-fluoro-benzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.15 g) as a yellow oil.

Aufarbeitung

  1. additionOn completion of the addition
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25%

Quellen und Nachweise

ORD-Eintrag
ord-a0b25da223354251ba1fe580f2772d14
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290472B2

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