Pyridinium, 1-(2-ethoxy-2-oxoethyl)-, bromide (1:1) → Methyl (4-(6-(1-((tert-butoxycarbonyl)amino)but-3-en-1-yl)-2-oxo-1,2-dihydropyridin-4-yl)-3-nitrophenyl)carbamate

HRID 1481278Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481278
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:28][CH:29]=[CH2:30])[C:10](=O)/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:23])[O:21][CH3:22])=[CH:15][C:14]=1[N+:24]([O-:26])=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-].C(O[C:35](=[O:43])[CH2:36][N+]1C=CC=CC=1)C.C([O-])(=O)C.[NH4+:48]>CCO>[C:1]([O:5][C:6]([NH:8][CH:9]([C:10]1[NH:48][C:35](=[O:43])[CH:36]=[C:12]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:23])[O:21][CH3:22])=[CH:15][C:14]=2[N+:24]([O-:26])=[O:25])[CH:11]=1)[CH2:28][CH:29]=[CH2:30])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 87028Pyridinium, 1-(2-ethoxy-2-oxoethyl)-, bromide (1:1)HCID 517165Ammonium AcetateHCID 90060454Methyl (4-((1E,4S)-4-((tert-butoxycarbonyl)amino)-3-oxohepta-1,6-dien-1-yl)-3-nitrophenyl)carbamate

Produkt 1

HCID 122466939Methyl (4-(6-(1-((tert-butoxycarbonyl)amino)but-3-en-1-yl)-2-oxo-1,2-dihydropyridin-4-yl)-3-nitrophenyl)carbamateAusbeute 67,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of 5F (3.0 g, 7.15 mmol) and 1-(2-ethoxy-2-oxoethyl)pyridinium bromide (1.189 g, 7.15 mmol) in EtOH (130 mL), was added ammonium acetate (11.03 g, 143 mmol) portion wise. After 15 min, the mixture was stirred at 75° C. The reaction mixture was then concentrated and dissolved in EtOAc. The organic layer was then washed with 1.0 N HCl, H2O, saturated sodium bicarbonate solution and finally by brine. The organic phase was dried over sodium sulfate, filtered and concentrated to yield a residue which was purified by normal phase chromatography to isolate 5G (2.2 g, 67%) as a brown solid. MS (ESI) m/z: 459.3 (M+H)+. The racemate was subjected to chiral separation using chiral AD-H 21×250 mm, eluting with a mixture of 35% (50/50 EtOH, i-PrOH and 0.1% DEA) and 65% CO2 with a flow rate of 70 mL/min and 150 bar at 40° C. to give enantiomer 5G1 (peak 1) and enantiomer 5G2 (peak 2).

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutiondissolved in EtOAc
  3. washThe organic layer was then washed with 1.0 N HCl, H2O, saturated sodium bicarbonate solution and finally by brine
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a residue which
  8. customwas purified by normal phase chromatography

Quellen und Nachweise

ORD-Eintrag
ord-b09c067aba7d4b78bfc24732104cbe8c
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409908B2

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