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

HRID 336328노트

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HRID 336328 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
85 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-004068bccf494c498de3e23a2d860882
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889671B2

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