1-Acetoxy-2-bromoethane → Acetic acid 2-{4-[2-(2,5-dichloro-phenoxy)-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-ethyl ester

HRID 1877400Notes

Reaction equation

HRID 1877400 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH2:15][CH2:14]2)=[O:12])=[CH:9][CH:8]=[CH:7][N:6]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Br[CH2:35][CH2:36][O:37][C:38](=[O:40])[CH3:39]>CN(C=O)C>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:35][CH2:36][O:37][C:38](=[O:40])[CH3:39])[CH2:15][CH2:14]2)=[O:12])=[CH:9][CH:8]=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 135641-Acetoxy-2-bromoethaneHCID 21226445Aluminium lithium hydrideHCID 59294486[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 59294552Acetic acid 2-{4-[2-(2,5-dichloro-phenoxy)-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-ethyl esterYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [2-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (24 mg, 0.06 mmol, 1.0 equiv; Example 122) in anhydrous DMF (1 mL) was added lithium aluminum hydride (2.3 mg, 0.06 mmol, 1.0 equiv; [CAS RN 16853-85-3]) and the reaction mixture stirred at rt. After 30 min, acetic acid 2-bromo-ethyl ester (12.0 mg, 8 μL, 0.072 mmol, 1.2 equiv; [CAS RN 927-68-4]) was added and the reaction mixture heated by microwave irradiation to 180° C. for 60 min. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μM, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 8.9 mg (31%) of the title compound as a light yellow powder. MS (ISP): 486.1 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated by microwave irradiation to 180° C. for 60 min
  2. customRemoval of the solvent mixture
  3. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μM, 19×50 mm column
  4. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  5. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-e73343fe36c14dd1a6c8ceed3df06c2e
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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