Diisopropylethylamine → Methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoate

HRID 1913336Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1913336
FC(F)(F)C(O)=O.[CH2:8]1[C:10]2([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH2:9]1.CCN(C(C)C)C(C)C.[F:25][C:26]([F:37])([CH3:36])[CH2:27][C@H:28]([N:33]=[C:34]=[O:35])[C:29]([O:31][CH3:32])=[O:30]>ClC(Cl)C.ClCCl>[CH2:9]1[C:10]2([CH2:15][CH2:14][N:13]([C:34]([NH:33][C@@H:28]([CH2:27][C:26]([F:25])([F:37])[CH3:36])[C:29]([O:31][CH3:32])=[O:30])=[O:35])[CH2:12][CH2:11]2)[CH2:8]1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 57946243Methyl (S)-4,4-difluoro-2-isocyanatopentanoateHCID 666613976-Azaspiro[2.5]octane trifluoroacetate

Produkt 1

HCID 57946179Methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 63651,1-DichloroethaneLösungsmittel2×

Versuchsvorschrift

A solution of 0.75 g of 6-azaspiro[2.5]octane trifluoroacetate (3.30 mmol, 1 eq.) and 0.75 ml of DIPEA (1.3 eq.) in 6 ml of dichloroethane was added under argon to a solution of 0.65 g of methyl (S)-4,4-difluoro-2-isocyanatopentanoate (3.36 mmol) in 4 ml of dichloroethane. The reaction mixture was stirred at RT overnight. The mixture was diluted with 10 ml of dichloromethane and washed with saturated NaHCO3 solution. The organic phase was dried over MgSO4 and then concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA. The product-containing fractions were combined and freeze-dried.

Aufarbeitung

  1. washwashed with saturated NaHCO3 solution
  2. dry with materialThe organic phase was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue thus obtained
  5. customwas purified by preparative HPLC (gradient
  6. additionacetonitrile/water and addition of 0.05% TFA
  7. customfreeze-dried

Quellen und Nachweise

ORD-Eintrag
ord-75891ce8591e4fbaa98b10c34b26b619
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609681B2

Notizen zur Reaktion

Wird geladen…