(+)-Glycidol → [4-((S)-2,3-dihydroxy-propyl)-piperazin-1-yl]-methanone

HRID 1894349ノート

反応式

HRID 1894349 の反応式
C(C1N=C(OCC)C(C2N([C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[O:36])C(C3C=CC(Cl)=CC=3)(C)C(C3C=CC(Cl)=CC=3)(C)N=2)=CN=1)(C)(C)C.[CH2:43]1[O:45][C@@H:44]1[CH2:46][OH:47]>C(O)C>[OH:45][C@H:44]([CH2:46][OH:47])[CH2:43][N:40]1[CH2:39][CH2:38][N:37]([CH:35]=[O:36])[CH2:42][CH2:41]1

参加物

4

反応物 2

HCID 5460455(+)-GlycidolHCID 67205751[2-(2-tert-Butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone

生成物 1

HCID 94253171[4-((S)-2,3-dihydroxy-propyl)-piperazin-1-yl]-methanone収率 185.9%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
120 °C

実験手順

The mixture of [2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (170 mg, 0.28 mmol) and R-glycidol (63 mg, 0.84 mmol) in ethanol (1 mL) was heated in the microwave at 120° C. for 10 min. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Purification of the crude residue by flash column chromatography (silica gel, eluting with 0-20% methanol in ethyl acetate) gave cis-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-((S)-2,3-dihydroxy-propyl)-piperazin-1-yl]-methanone (98 mg). The diastereomers were then separated by supercritical fluid chromatography (Berger Instrument Multi-Gram II, Daicel ChiralPak OD-H 3×25 cm, 35° C. at 100 bar, eluting with 25% ethanol in carbon dioxide) to give the title compound (post peak, 40 mg). HR-MS (ES, m/z) calculated for C35H45N6O4Cl2 [(M+H)+] 683.2874, observed 683.2871.

後処理

  1. temperatureUpon cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customPurification of the crude residue
  4. washby flash column chromatography (silica gel, eluting with 0-20% methanol in ethyl acetate)

出典と根拠

ORDレコード
ord-76fcb015f9c84e778430dae66a92801d
出典データセット
uspto-grants-2013_08
特許番号
US08513239B2

反応ノート

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