Hydroxylamine → Ethyl 2-(2-ethoxy-2-oxoethyl)-8,8-dimethyl-2,5,6,8-tetrahydro-[1,2,4]oxadiazolo[3,2-c][1,4]oxazine-2-carboxylate

HRID 348113Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 348113
Cl[CH2:2][CH2:3][O:4][C:5]([CH3:9])([CH3:8])[C:6]#[N:7].[Na+].[I-].[NH2:12][OH:13].[C:14]([C:21]([O:23][CH2:24][CH3:25])=[O:22])#[C:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]>C(O)C.C(OCC)(=O)C>[CH2:19]([O:18][C:16](=[O:17])[CH2:15][C:14]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[O:13][N:12]2[C:6]([C:5]([CH3:9])([CH3:8])[O:4][CH2:3][CH2:2]2)=[N:7]1)[CH3:20]

Komponenten

7

Edukt 4

HCID 787HydroxylamineHCID 5238Sodium IodideHCID 69803Diethyl acetylenedicarboxylateHCID 210697862-(2-Chloroethoxy)-2-methylpropanenitrile

Produkt 1

HCID 21069948Ethyl 2-(2-ethoxy-2-oxoethyl)-8,8-dimethyl-2,5,6,8-tetrahydro-[1,2,4]oxadiazolo[3,2-c][1,4]oxazine-2-carboxylateAusbeute 48,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of intermediate 23, 2-(2-chloroethoxy)-2-methylpropanenitrile (14.7 g, 0.10 mole) and NaI (1.5 g, 10 mmol) in ethanol (50 mL) was added an aqueous solution (50%) of hydroxylamine (18.4 g, 0.30 mole) resulting in an exothermic reaction. Following this the reaction mixture was heated at 80° C. for 2 h. Upon cooling to room temperature the solvent was removed. The resulting residue was dissolved in 1:1 ethanol/H2O (100 mL) and cooled in an ice bath. To this was added diethyl acetylenedicarboxylate (17.6 mL, 0.110 mole) over 10 min. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. Following this, it was diluted with ethyl acetate (250 mL), washed with H2O (2×100 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to give the crude product as a yellow oil. Flash chromatography on a silica gel column, eluting with 20–40% ethyl acetate/Hexanes, provided the title compound as a viscous pale yellow oil (15.29 g, 48.6% yield). 1H NMR (500 MHz, CDCl3) δ ppm: 4.35–4.28 (2H, m), 4.18–4.12 (2H, m), 3.60–3.56 (1H, m), 3.51–3.47 (1H, m), 3.30 (1H, d, J=16.2 Hz), 2.94 (1H, d, J=16.2 Hz), 1.52 (3H, s), 1.51 (3H, s), 1.29 (3H, t, J=7.0 Hz), 1.24 (3H, t, J=7.0 Hz). LCMS (M+H) calcd for C14H23N2O7: 315.16; found: 315.33.

Aufarbeitung

  1. customresulting in an exothermic reaction
  2. temperatureUpon cooling to room temperature the solvent
  3. customwas removed
  4. dissolutionThe resulting residue was dissolved in 1:1 ethanol/H2O (100 mL)
  5. temperaturecooled in an ice bath
  6. temperatureto warm to room temperature
  7. washwashed with H2O (2×100 mL), brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product as a yellow oil
  12. washFlash chromatography on a silica gel column, eluting with 20–40% ethyl acetate/Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-cf0e51edf829479a8d29382b730644dd
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176196B2

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