Dimethyl Sulfide → (3RS,4R)-2-Methyl-4-(trityl-amino)-hexan-3-ol

HRID 729568Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 729568
S(C)C.[CH:4]([Li])([CH3:6])[CH3:5].[C:8]([NH:27][C@H:28]([CH2:31][CH3:32])[CH:29]=[O:30])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH4+].[Cl-]>CCOCC>[CH3:5][CH:4]([CH:29]([OH:30])[C@H:28]([NH:27][C:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:31][CH3:32])[CH3:6]

Komponenten

6

Edukt 4

HCID 1068Dimethyl SulfideHCID 25517Ammonium ChlorideHCID 57714153(R)-2-(Trityl-amino)-butyraldehydeHCID 178506895HCID 178506895, Verbindung

Produkt 1

HCID 57714161(3RS,4R)-2-Methyl-4-(trityl-amino)-hexan-3-ol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel2×

Versuchsvorschrift

To a stirred suspension of CuBr.SMe2 (1.37 g, 2.2 eq, 6.66 mmol) in Et2O (100 mL) under an argon atmosphere at −78° C., was added isopropyllithium (0.7 M in pentane, 17.29 mL, 4 eq, 12.1 mmol) dropwise, and the solution allowed to warm to room temperature. The mixture was recooled to −70° C., to which was added a solution of (R)-2-(trityl-amino)-butyraldehyde (1 g, 1 eq, 3.03 mmol) in Et2O (25 mL) dropwise with stirring. The reaction mixture was stirred at this temperature for 1 h, then allowed to warm to −55° C. and stirred at this temperature for 3 h. To the reaction mixture was added a saturated aqueous solution of NH4Cl (100 mL) and allowed to warm to room temperature over 16 h. The reaction mixture was extracted with Et2O (2×200 mL), and the combined organic phase washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by silica gel gradient column chromatography, eluted with hexane:ether (100:0→90:10) to afford the title compound as a colourless oil. Yield: 0.53 g (47%). (50% de 3S,4R: 50% de 3R,4R) 1H-NMR (d6-DMSO, 250 MHz): δ 0.44 (t, 3H, J=7.03 Hz, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 0.52 & 0.77 (2×d, 6H, J=6.48 Hz, —NHCH (CH2CH3)CH(CH(CH3)2)OH), 0.79-1.13 (m, 2H, —NHCH(CH2CH3)CH (CH(CH3)2)OH), 1.72 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 2.11 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 2.77 (m, 1H, —NH CH(CH2CH3)CH (CH(CH3)2)OH), 2.99 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 4.55 (d, 1H, J=5.21 Hz, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 7.15-7.46 (m, 15H, 3×Ph).

Aufarbeitung

  1. customwas recooled to −70° C., to which
  2. stirringThe reaction mixture was stirred at this temperature for 1 h
  3. temperatureto warm to −55° C.
  4. stirringstirred at this temperature for 3 h
  5. temperatureto warm to room temperature over 16 h
  6. extractionThe reaction mixture was extracted with Et2O (2×200 mL)
  7. washthe combined organic phase washed with brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customThe residue was purified by silica gel gradient column chromatography
  11. washeluted with hexane:ether (100:0→90:10)

Quellen und Nachweise

ORD-Eintrag
ord-2f66c8bba10743339db8143d4d19fa85
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07582642B2

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