(2R)-3,6-diethoxy-2-(propan-2-yl)-2,5-dihydropyrazine → (2S,5R)-2-((S)-2-(benzyloxymethyl)-3-methylbutyl)-3,6-diethoxy-5-isopropyl-2,5-dihydropyrazine

HRID 660380Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 660380
[CH2:1]([O:3][C:4]1[C@@H:5]([CH:13]([CH3:15])[CH3:14])[N:6]=[C:7]([O:10][CH2:11][CH3:12])[CH2:8][N:9]=1)[CH3:2].[Li]CCCC.Br[CH2:22][C@@H:23]([CH:33]([CH3:35])[CH3:34])[CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[CH2:26]([O:25][CH2:24][C@H:23]([CH:33]([CH3:35])[CH3:34])[CH2:22][C@H:8]1[C:7]([O:10][CH2:11][CH3:12])=[N:6][C@H:5]([CH:13]([CH3:15])[CH3:14])[C:4]([O:3][CH2:1][CH3:2])=[N:9]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Komponenten

5

Edukt 3

HCID 5325957(2R)-3,6-diethoxy-2-(propan-2-yl)-2,5-dihydropyrazineHCID 117159911-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzeneHCID 178418339Butyllithium

Produkt 1

HCID 68784201(2S,5R)-2-((S)-2-(benzyloxymethyl)-3-methylbutyl)-3,6-diethoxy-5-isopropyl-2,5-dihydropyrazineAusbeute 82,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of (R)-3,6-diethoxy-2-isopropyl-2,5-dihydropyrazine (15.4 g, 0.084 mol) in anhydrous THF (250 mL) at −78° C. was added dropwise 2.5 M n-BuLi in hexanes (34 mL, 0.085 mol) over 45 min. After stirring for 30 min at −78° C., a solution of (S)-((2-(bromomethyl)-3-methylbutoxy)methyl)benzene (15.6 g, 0.056 mol) in THF (100 L) was added dropwise over 30 min. The mixture was stirred for 2 h at −78° C. and then at −20° C. for 18 h. After evaporation, the residue was partitioned between H2O (200 mL) and EtOAc (3×200 mL). The combined organic layers were washed with brine (0.5 L), dried over MgSO4, evaporated, and purified by flash chromatography on silica gel eluting with 1:25 EtOAc/hexane to give (2S,5R)-2-((S)-2-(benzyloxymethyl)-3-methylbutyl)-3,6-diethoxy-5-isopropyl-2,5-dihydropyrazine (18.5 g, 80%). 1H NMR (400 MHz, CDCl3): δ8.00 (s, 1H), 7.34-7.24 (m, 5H), 4.50 (s, 2H), 4.03 (m, 1H), 3.93 (m, 1H), 3.72 (s, 3H), 3.62 (s, 3H), 3.54-3.42 (m, 2H), 2.27 (m, 1H), 1.94-1.88 (m, 1H), 1.80-1.61 (m, 1H), 1.47-1.42 (m, 1H), 1.05 (d, J=6.4 Hz, 3H), 0.88 (d, J=6.4 Hz, 3H), 0.80 (d, J=6.4 Hz, 3H), 0.68 (d, J=6.4 Hz, 3H); MS: 403 (M++1).

Aufarbeitung

  1. stirringThe mixture was stirred for 2 h at −78° C.
  2. waitat −20° C. for 18 h
  3. customAfter evaporation
  4. customthe residue was partitioned between H2O (200 mL) and EtOAc (3×200 mL)
  5. washThe combined organic layers were washed with brine (0.5 L)
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. custompurified by flash chromatography on silica gel eluting with 1:25 EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-f218c04165034674ab352d8f3c06d8b3
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084485B2

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