Ethyl Acetate → 2-(2-Bromoethoxy)ethyl 2-fluoro-3-morpholinobenzoate

HRID 577273Notes

Reaction equation

HRID 577273 reaction equation
[NH2:1][C:2]1[C:3]([F:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].CCN(C(C)C)C(C)C.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26][Br:27].[CH3:28][CH2:29][O:30][C:31]([CH3:33])=O>CN(C=O)C>[F:11][C:3]1[C:2]([N:1]2[CH2:33][CH2:31][O:30][CH2:29][CH2:28]2)=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([O:7][CH2:22][CH2:23][O:24][CH2:25][CH2:26][Br:27])=[O:6]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 21521Bis(2-bromoethyl) etherHCID 81531DiisopropylethylamineHCID 230943433-Amino-2-fluorobenzoic acid

Product 1

HCID 667651712-(2-Bromoethoxy)ethyl 2-fluoro-3-morpholinobenzoateYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-amino-2-fluorobenzoic acid (500 mg, 3.1 mmol) in DMF (10 mL) was added DIEA (4.5 mL) and 2-bromoethylether (5 eq) and the reaction heated to 80° C. for 18 h. The reaction was allowed to cool to rt, diluted with EtOAc and washed with saturated NH4Cl (aq). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was purified by column chromatography (petroleum ether: EtOAc) to give 2-(2-bromoethoxy)ethyl 2-fluoro-3-morpholinobenzoate (450 mg, 38%) as a yellow oil.

Workup

  1. temperatureto cool to rt
  2. washwashed with saturated NH4Cl (aq)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by column chromatography (petroleum ether: EtOAc)

Sources & evidence

ORD record
ord-fed85b1e9e1c4d179e06d2de493b667b
Source dataset
uspto-grants-2015_05
Patent number
US09040545B2

Reaction notes

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