Ethanol → Dichloromethane methanol ammonium hydroxide

HRID 2044965Notes

Reaction equation

HRID 2044965 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH:19]([N:21]1[C:29](=[O:30])C3C(=CC=CC=3)C1=O)[CH3:20])[C:6]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)=[N:7]2.C([OH:34])C.NN.[CH2:37]([Cl:39])[Cl:38]>>[CH2:37]([Cl:39])[Cl:38].[CH3:29][OH:30].[NH4+:7].[OH-:34].[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH:19]([NH2:21])[CH3:20])[C:6]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)=[N:7]2

Participants

6

Reactant 4

HCID 702EthanolHCID 6344DichloromethaneHCID 9321HydrazineHCID 577079992-(1-(5-Chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 577078041-(5-Chloro-2-(3-fluorophenyl)quinolin-3-yl)ethanamine

Procedure

To a suspension of 2-(1-(5-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)-isoindoline-1,3-dione (1.1115 g, 2.580 mmol) in ethanol (51.59 mL, 2.580 mmol) was added hydrazine, anhydrous (0.8097 mL, 25.80 mmol), and the mixture was stirred under reflux. After 1 h, the mixture was cooled to room temperature. The mixture was diluted with CH2Cl2 (50 mL), filtered to removed the precipitated byproduct, and washed the filtered solid with CH2Cl2 (50 mL). The filtrate containing the desired product was concentrated under reduced pressure. The residue was purified by column chromatography on a 80 g of Redi-Sep™ column using 0% to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 25 min, and then 100% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) for 4 min as eluent to give 1-(5-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethanamine as a yellow syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.87 (1 H, s), 7.97-8.02 (1 H, m), 7.78-7.82 (1 H, m), 7.73 (1 H, dd, J=8.4, 7.6 Hz), 7.52-7.61 (1 H, m), 7.41-7.50 (2 H, m), 7.31-7.39 (1 H, m), 4.29 (1 H, q, J=6.7 Hz), 2.10 (2 H, br. s.), 1.19 (3 H, d, J=6.7 Hz); LC-MS (ESI) m/z 301.1 [M+H]+.

Workup

  1. temperatureunder reflux
  2. filtrationfiltered
  3. customto removed the precipitated byproduct
  4. washwashed the filtered solid with CH2Cl2 (50 mL)
  5. additionThe filtrate containing the desired product
  6. concentrationwas concentrated under reduced pressure
  7. customThe residue was purified by column chromatography on a 80 g of Redi-Sep™ column
  8. customover 25 min

Sources & evidence

ORD record
ord-28b8db310e644586ba0c2f6d1e01a66d
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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