Water → Dehydroaripiprazole

HRID 43237

Reaction equation

HRID 43237 reaction equation
[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

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 60795Aripiprazole

Product 1

HCID 10114519DehydroaripiprazoleYield 102.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-afcb54bcb171469d92f46f5b1b8abf8c
Source dataset
uspto-grants-2013_09
Patent number
US08536328B2

Linked notes

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