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 1372216

반응식

HRID 1372216 반응식
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]

참가 물질

7

반응물 4

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

생성물 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-carboxylate수율 48.6%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e4123ddae9b84a8fb69f44ef5c77224e
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07157447B2

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