Oxalic Acid → 1-(3,9-Dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl) propan-2-ol

HRID 1045572Notes

Reaction equation

HRID 1045572 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:17][CH2:16][C:15]2[C:14]3[CH:13]=[C:12]([CH3:18])[CH:11]=[CH:10][C:9]=3[NH:8][C:7]=2[CH2:6][CH2:5]1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2([CH3:29])[CH2:28][O:27]2)=[CH:22][CH:21]=1.C(O)(=O)C(O)=O>CN(C=O)C.C1COCC1.O>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([OH:27])([CH3:28])[CH2:29][N:8]2[C:9]3[CH:10]=[CH:11][C:12]([CH3:18])=[CH:13][C:14]=3[C:15]3[CH2:16][CH2:17][N:4]([CH3:3])[CH2:5][CH2:6][C:7]2=3)=[CH:24][CH:25]=1

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 24758Sodium hydrideHCID 178694862-(4-Fluorophenyl)-2-methyloxiraneHCID 685600921,2,3,4,5,6-Hexahydro-3,9-dimethylazepino[4,5-b]indole

Product 1

HCID 593683271-(3,9-Dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl) propan-2-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared by following general procedure 5. To a stirred suspension of sodium hydride (67 mg, 0.28 mmol) in 5 mL of DMF, 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.2 g, 0.934 mmol) was added and stirred at RT for 5 min. 2-(4-Fluorophenyl)-2-methyloxirane (212 mg, 1.39 mmol) was added slowly dropwise and stirred at RT for 14 h. The reaction was monitored by TLC and LCMS. After completion of the reaction, water was added, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, evaporated under reduced pressure and purified by column chromatography using 10% methanol-DCM. The freebase (30 mg, 0.082 mmol) was dissolved in THF (1.0 mL) and oxalic acid (10 mg, 0.082 mmol) in THF (1.0 mL) was added slowly, the mixture was stirred at RT for 20 min. and the formed solid was filtered, washed with ether and dried to afford the product as oxalate salt (15 mg, brown solid).

Workup

  1. additionwas added
  2. stirringstirred at RT for 14 h
  3. additionwas added
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. custompurified by column chromatography
  8. dissolutionThe freebase (30 mg, 0.082 mmol) was dissolved in THF (1.0 mL)
  9. stirringthe mixture was stirred at RT for 20 min.
  10. filtrationthe formed solid was filtered
  11. washwashed with ether
  12. customdried

Sources & evidence

ORD record
ord-3860a0f32be64314b5b0f04b47107fd2
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

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