Cyanomethylenetributylphosphorane → tert-butyl (3R,9aS)-3-methyl-3-[(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

HRID 1501961노트

반응식

HRID 1501961 반응식
O[CH2:2][C@@H:3]1[N:8]([CH2:9][C:10]([OH:24])([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C:18](=[O:22])[O:17][C@@H:16]([CH3:23])[CH2:15]3)[CH3:11])[CH2:7][CH2:6][N:5]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:4]1.C(C=P(CCCC)(CCCC)CCCC)#N>C1C=CC=CC=1>[CH3:11][C@:10]1([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C:18](=[O:22])[O:17][C@H:16]([CH3:23])[CH2:15]3)[O:24][CH2:2][C@@H:3]2[CH2:4][N:5]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:6][CH2:7][N:8]2[CH2:9]1

참가 물질

4

반응물 2

HCID 4622928CyanomethylenetributylphosphoraneHCID 131734287HCID 131734287, 화합물

생성물 1

HCID 89633412tert-butyl (3R,9aS)-3-methyl-3-[(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

시약·촉매·용매 1

HCID 241Benzene용매

실험 절차

A sealed tube containing tert-butyl (3R)-3-(hydroxymethyl)-4-{2-hydroxy-2-[(3S)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]propyl}piperazine-1-carboxylate (175 mg, 0.403 mmol) and cyanomethylenetributylphosphorane (117 mg, 0.483 mmol) dissolved in anhydrous benzene (3 mL) was degassed twice with nitrogen and then heated using a microwave to 135° C. for 2.5 hours. The reaction was allowed to cool and the crude mixture was concentrated and purified on MPLC (30-75% EtOAc/Hex) to afford the minor isomer as the faster eluting peak and the major isomer as the slower eluting peak: Major, slower eluting isomer: LC-MS: (M+1)+417.

후처리

  1. customwas degassed twice with nitrogen
  2. temperatureheated
  3. customto 135° C.
  4. customfor 2.5 hours
  5. temperatureto cool
  6. concentrationthe crude mixture was concentrated
  7. custompurified on MPLC (30-75% EtOAc/Hex)
  8. customto afford the minor isomer as the
  9. washfaster eluting peak
  10. washthe major isomer as the slower eluting peak
  11. washMajor, slower eluting isomer

출처 및 근거

ORD 기록
ord-b0663125cd4c44c396b8ca1531416086
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206199B2

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