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

HRID 1683319ノート

反応式

HRID 1683319 の反応式
[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

参加物

8

反応物 4

HCID 8471Triethylamine2 回HCID 31297Methanesulfonyl chloride2 回HCID 21226129Dichloromethane methanolHCID 22491366Racemic (7S*,9aS*)-2-(Benzo[d]isoxazol-3-yl)perhydro-7-(hydroxymethyl)-1H-pyrido[1,2-a]pyrazine

生成物 1

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

試薬・触媒・溶媒 3

HCID 170165Iodoplatinate触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒4 回

反応条件

温度
5 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-74c3009db3ae43acaadc0bcef15f2965
出典データセット
uspto-grants-1997_06
特許番号
US05637713

反応ノート

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