Triethylamine → Racemic (7R*,9aS*)-2-(Benzo[d]isoxazol-3-yl)-perhydro-7-(methanesulfonyloxymethyl)-1H-pyrido[1,2-a]pyrazine

HRID 1683319노트

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HRID 1683319 반응식
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]3[CH2:16][CH:17]([CH2:20][OH:21])[CH2:18][CH2:19][CH:12]3[CH2:11]2)=[N:2]1.C(N(CC)CC)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31].C(Cl)Cl.CO>C(Cl)Cl.[H+].[H+].[Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[I-].[Pt].O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]3[CH2:16][CH:17]([CH2:20][O:21][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:18][CH2:19][CH:12]3[CH2:11]2)=[N:2]1

참가 물질

8

반응물 4

HCID 8471Triethylamine2회HCID 31297Methanesulfonyl chloride2회HCID 21226129Dichloromethane methanolHCID 22491366Racemic (7S*,9aS*)-2-(Benzo[d]isoxazol-3-yl)perhydro-7-(hydroxymethyl)-1H-pyrido[1,2-a]pyrazine

생성물 1

HCID 19699662Racemic (7R*,9aS*)-2-(Benzo[d]isoxazol-3-yl)-perhydro-7-(methanesulfonyloxymethyl)-1H-pyrido[1,2-a]pyrazine수율 90.2%

시약·촉매·용매 3

HCID 170165Iodoplatinate촉매HCID 962Water용매HCID 6344Dichloromethane용매4회

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온도
5 °C

실험 절차

To a chilled (5° C.) end stirred slurry of the alcohol title product of Example 7 (154.0 g, 0.54 mol) and triethylamine (81.76 ml, 59.6 g, 0.589 mol) in methylene chloride (3.0 liters), a solution of methanesulfonyl chloride (43.55 ml, 64.5 g, 0.563 mol) in methylene chloride (350 ml) was added dropwise ever 30 minutes. TLC monitoring (methylene chloride/methanol=9:1 in volume; iodoplatinate spray) of the reaction mixture after an additional 1/2 hour of stirring indicated incomplete reaction. Complete reaction was realized within 1/2 hour after addition of a second portion of triethylamine (8.23 ml, 6.0 g, 59.3 mmol) and methanesulfonyl chloride (4.32 ml, 6.4 g, 55.9 mmol) added dropwise as a methylene chloride (20 ml) solution. Water (3 liters) and methylene chloride (1.5 liters) were added, and the biphasic mixture was vigorously stirred prior to separation of the organic and aqueous phases. The aqueous portion was then extracted with a fresh portion of methylene chloride (1.5 liters). The organic extracts were then combined, washed with brine (twice with 2 liter portions) and dried over anhydrous sodium sulfate. Concentration in vacuo afforded the present title compound as a tan solid (178.0 g, 90.2% yield). TLC Rf (methylene chloride/methanol=9:1 in volume; iodoplatinate spray): 0.24. MS m/z 365.1 (M, C17H23N3O4S). 13CNMR (CDCl3) delta 164.0, 160.9, 129.6, 122.4, 122.1, 116.0, 110.5, 71.9, 59.9, 57.7, 54.0, 53.3, 48.1, 37.4, 35.9, 28.4, 26.2.

후처리

  1. customreaction
  2. customComplete reaction
  3. customto separation of the organic and aqueous phases
  4. extractionThe aqueous portion was then extracted with a fresh portion of methylene chloride (1.5 liters)
  5. washwashed with brine (twice with 2 liter portions) and
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration in vacuo

출처 및 근거

ORD 기록
ord-74c3009db3ae43acaadc0bcef15f2965
출처 데이터셋
uspto-grants-1997_06
특허 번호
US05637713

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