2-Fluorophenol → Ethyl 2-(2-fluorophenoxy)propanoate

HRID 1985127Notes

Reaction equation

HRID 1985127 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14].Br[CH:16]([CH3:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18]>CN(C=O)C.C(OCC)C>[CH2:20]([O:19][C:17](=[O:18])[CH:16]([O:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[F:7])[CH3:22])[CH3:21]

Participants

6

Reactant 3

HCID 97072-FluorophenolHCID 10796Cesium carbonateHCID 79040Ethyl 2-bromopropionate

Product 1

HCID 57719284Ethyl 2-(2-fluorophenoxy)propanoateYield 94.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Cesium carbonate (65.69 g, 201.61 mmol) is added to a solution of 2-fluorophenol (9 mL, 100.84 mmol, d=1.256) in anhydrous DMF (300 mL) at room temperature under an atmosphere of nitrogen. After five minutes, ethyl 2-bromopropionate (130.1 mL, 100.84 mmol, d=1.394) is added rapidly dropwise and the resultant mixture is allowed to stir at 90° C. for 18 h. The reaction mixture is diluted with diethyl ether, then extracted twice with 1N HCl and twice with water. The organic layer is dried, concentrated, and purified by flash chromatography (25% ether in hexanes) to provide the titled compound (20.14 g, 94%). 1H NMR (400 MHz, CDCl3): □. 7.07-6.96 (m 2H), 6.93-6.87 (m, 2H), 4.73, 4.71 (ABq, 1H, J=6.7 Hz). 4.21-4.15 (m, 2H), 1.61 (d, 3H, J=6.7 Hz), 1.21 (t, 3H, J=6.7 Hz). MS [EI+] 507 (M+H)+.

Workup

  1. extractionextracted twice with 1N HCl and twice with water
  2. customThe organic layer is dried
  3. concentrationconcentrated
  4. custompurified by flash chromatography (25% ether in hexanes)

Sources & evidence

ORD record
ord-e28f655e103743dab4ceb17b936112ca
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

Loading…