Triethylamine → tert-Butyl 4-(5-(methoxycarbonyl)thiophene-2-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 471030

Reaktionsgleichung

Reaktionsgleichung von HRID 471030
Cl.[O:2]1[C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][NH:5][CH2:4][CH2:3]1.[S:20]1[C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=[C:21]1[C:28]([OH:30])=[O:29].[CH2:31](N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:31][O:30][C:28]([C:21]1[S:20][C:24]([C:25]([N:5]2[CH2:6][C:7]3([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]3)[O:2][CH2:3][CH2:4]2)=[O:27])=[CH:23][CH:22]=1)=[O:29]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 202732,5-Thiophenedicarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66964240Tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

Produkt 1

HCID 57988893tert-Butyl 4-(5-(methoxycarbonyl)thiophene-2-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (WuXi PharmaTech) (0.6 g) and thiophene-2,5-dicarboxylic acid (1.7 g) in DMF (10 mL) was treated with triethylamine (2.75 mL) and cooled to 0° C. HATU (1.013 g) was added and the mixture stirred at 20° C. for 2 hours. The mixture was partitioned between ethyl acetate and brine containing acetic acid (2 mL), the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The residue was purified by flash silica chromatography using 1% acetic acid in ethyl acetate as solvent. This material was dissolved in THF (30 mL), treated with carbonyldiimidazole (0.332 g) and the mixture was allowed to stand at 45° C. for 1 hour. Methanol (20 mL) was added and the reaction heated at 50° C. for 30 minutes. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 40% ethyl acetate in isohexane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.45 g.

Aufarbeitung

  1. customThe mixture was partitioned between ethyl acetate and brine
  2. additioncontaining acetic acid (2 mL)
  3. washthe organic layer was washed twice with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe residue was purified by flash silica chromatography
  8. dissolutionThis material was dissolved in THF (30 mL)
  9. additiontreated with carbonyldiimidazole (0.332 g)
  10. waitto stand at 45° C. for 1 hour
  11. additionMethanol (20 mL) was added
  12. temperaturethe reaction heated at 50° C. for 30 minutes
  13. customThe solvent was removed under reduced pressure
  14. customthe residue was partitioned between ethyl acetate and brine
  15. dry with materialThe organic layer was dried over sodium sulphate
  16. filtrationfiltered
  17. customthe solvent evaporated under reduced pressure
  18. customThe crude product was purified by flash silica chromatography
  19. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-39a5537024134770aa8138a0441eb760
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629271B2

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