Water → Dehydroaripiprazole

HRID 43237

反応式

HRID 43237 の反応式
[CH:1]1[CH:2]=[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]4[CH2:30][CH2:29][C:27](=[O:28])[NH:26][C:24]=4[CH:25]=3)[CH2:11][CH2:10]2)[C:4]([Cl:8])=[C:5]([Cl:7])[CH:6]=1.FC(F)(F)C(O)=O.O.[OH-].[Na+]>O1CCCC1>[CH2:11]1[N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]3[CH:30]=[CH:29][C:27]([NH:26][C:24]=3[CH:25]=2)=[O:28])[CH2:13][CH2:14][N:9]([C:3]2[CH:2]=[CH:1][CH:6]=[C:5]([Cl:7])[C:4]=2[Cl:8])[CH2:10]1

参加物

6

反応物 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 60795Aripiprazole

生成物 1

HCID 10114519Dehydroaripiprazole収率 102.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Aripiprazole (Formula VIA; 15 g, 0.03 mol) was dissolved in anhydrous tetrahydrofuran (360 mL). Trifluoroacetic acid (12 mL, 0.16 mol) was added to the clear solution. 1,2-Dichloro-4,5-dicyano quinone (24.3 g, 0.11 mol) was added and the mixture was stirred at room temperature under nitrogen atmosphere. The reaction was stirred for 40 minutes and TLC showed no starting material remaining Water (1.5 L) was added then reaction mixture basified with 50% aq NaOH until pH 12. The reaction mixture was extracted with dichloromethane (3×1 L) and the combined organics were dried (MgSO4) to give the crude product. This was purified by column chromatography on silica eluting with dichloromethane to 10% methanol/dichloromethane. The product was further purified by recrystallisation from 2-propanol to give the desired product (13.7 g, 92%) as an off white solid. 1H-NMR (400 MHz, CDCl3) δ 12.33 (1H, br s), 7.72 (1H, d), 7.42 (1H, d), 7.16-7.11 (2H, m), 6.98-6.93 (1H, dd), 6.83-6.79 (2H, m), 6.53 (1H, d), 4.10 (2H, t), 3.09 (4H, br s), 2.67 (4H, br s), 2.52 (2H, t), 1.93-1.70 (4H, m). LCMS (acidic method) [M+H]+ 446.02, rt 14.246 min.

後処理

  1. stirringThe reaction was stirred for 40 minutes
  2. additionwas added
  3. customreaction mixture
  4. extractionThe reaction mixture was extracted with dichloromethane (3×1 L)
  5. dry with materialthe combined organics were dried (MgSO4)
  6. customto give the crude product
  7. customThis was purified by column chromatography on silica eluting with dichloromethane to 10% methanol/dichloromethane
  8. customThe product was further purified by recrystallisation from 2-propanol

出典と根拠

ORDレコード
ord-afcb54bcb171469d92f46f5b1b8abf8c
出典データセット
uspto-grants-2013_09
特許番号
US08536328B2

関連ノート

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