Diisopropylethylamine → 3-chloro-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde

HRID 336328Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 336328
[Cl:1][C:2]1[C:6]2[CH:7]=[C:8]([CH:13]=[O:14])[C:9](F)=[C:10]([F:11])[C:5]=2[O:4][N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:24][C@H:25]1[O:30][C@@H:29]([CH3:31])[CH2:28][NH:27][CH2:26]1>C(#N)C>[Cl:1][C:2]1[C:6]2[CH:7]=[C:8]([CH:13]=[O:14])[C:9]([N:27]3[CH2:26][C@H:25]([CH3:24])[O:30][C@H:29]([CH3:31])[CH2:28]3)=[C:10]([F:11])[C:5]=2[O:4][N:3]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 6415002,6-Dimethylmorpholine, cis-HCID 866581203-Chloro-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde

Produkt 1

HCID 866581213-chloro-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To an ice cooled solution of 3-chloro-6,7-difluoro-1,2-benzoxazole-5-carbaldehyde (prepared according to the procedure described in International Application Publication No. WO 2010/043893, 5.0 g, 23.0 mmol) in anhydrous acetonitrile (50 ml) was added diisopropylethylamine (5.9 g, 45.9 mmol) followed by cis-2,6-dimethylmorpholine (2.6 g, 23.0 mmol) and the mixture was heated at 85° C. for 12 hours in a sealed tube. The solution was cooled to room temperature and the volatiles were removed under vacuum. The residue was dissolved in Ethyl acetate, washed with water followed by brine and then dried over anhydrous Na2SO4. Removal of solvent under vacuum afforded the crude product, which was purified over silica gel column using a gradient of ethyl acetate in pet. ether to give title compound as solid. Yield: 6.0 g (84%). 1H NMR (400 MHz, DMSO-d6) δ: 1.0 (d, 6H), 2.9 (t, 2H), 3.1 (d, 2H), 3.8 (m, 2H), 7.7 (s, 1H), 10.2 (s, 1H). MS (ES) MH+: 313 for C14H14ClFN2O3.

Aufarbeitung

  1. temperatureThe solution was cooled to room temperature
  2. customthe volatiles were removed under vacuum
  3. dissolutionThe residue was dissolved in Ethyl acetate
  4. washwashed with water
  5. dry with materialdried over anhydrous Na2SO4
  6. customRemoval of solvent under vacuum
  7. customafforded the crude product, which
  8. customwas purified over silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-004068bccf494c498de3e23a2d860882
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889671B2

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