Morpholine → Methyl 2-chloro-4-morpholin-4-ylbenzoate

HRID 1179231Notes

Reaction equation

HRID 1179231 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](F)=[CH:6][C:5]=1[Cl:11].[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:6][C:5]=1[Cl:11]

Participants

6

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 2763551Methyl 2-Chloro-4-fluorobenzoate

Product 1

HCID 3330270Methyl 2-chloro-4-morpholin-4-ylbenzoateYield 65%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-4-fluoro-benzoic acid methyl ester (3.51 g, 18.6 mmol), morpholine (1.95 mL, 22.3 mmol) and potassium carbonate (5.12 g, 37.1 mmol) in N-methylpyrrolidinone (20 mL) was stirred at 120° C. for 5 h. The reaction was cooled, diluted with ethyl acetate and filtered through Celite. The filtrate was washed four times with water, once with brine, was dried (sodium sulfate) and evaporated. Purification by flash chromatography (SiO2) eluted with 2:8 ethyl acetate:hexanes to provide 2-chloro-4-morpholin-4-yl-benzoic acid methyl ester (3.08 g, 65% yield) as a white solid. 1H-NMR (CDCl3, 500 MHz) 7.79 (d, 1H), 6.81 (d, 1H), 6.67 (dd, 1H), 3.81 (s, 3H), 3.78 (m, 4H), 3.20 (m, 4H) ppm; MS (FIA) 256.1 (M+H); HPLC (Method A) 3.275 min.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through Celite
  3. washThe filtrate was washed four times with water
  4. dry with materialonce with brine, was dried (sodium sulfate)
  5. customevaporated
  6. customPurification by flash chromatography (SiO2)
  7. washeluted with 2:8 ethyl acetate

Sources & evidence

ORD record
ord-1b024038256f47d5aeeb8ec9d4f386f8
Source dataset
uspto-grants-2007_10
Patent number
US07279469B2

Reaction notes

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