Methanol → methyl 3-chloro-2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-4-fluorobenzoate

HRID 577831Notes

Reaction equation

HRID 577831 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][C@H:16]([CH3:18])[O:15][C@H:14]([CH3:19])[CH2:13]2)=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6].OS(O)(=O)=O.[CH3:25]O>>[Cl:1][C:2]1[C:3]([N:12]2[CH2:13][C@H:14]([CH3:19])[O:15][C@H:16]([CH3:18])[CH2:17]2)=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([O:7][CH3:25])=[O:6]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 673589363-chloro-2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-4-fluorobenzoic acid2×

Product 1

HCID 67358498methyl 3-chloro-2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-4-fluorobenzoate

Procedure

To a stirred solution of 3-chloro-2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-4-fluorobenzoic acid (Intermediate 35, 10.0 g, 34.8 mmol) in methanol (50 mL) was added concentrated H2SO4 (1 mL) and the solution was refluxed for 12 hours. The reaction mixture was concentrated and diluted with EtOAc (100 mL). The organic layer washed with H2O (2×20 mL), dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography with ethyl acetate-pet. ether to give product as a solid. Yield: 9.0 g (86%)

Workup

  1. temperaturethe solution was refluxed for 12 hours
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with EtOAc (100 mL)
  4. washThe organic layer washed with H2O (2×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography with ethyl acetate-pet. ether
  8. customto give product as a solid

Sources & evidence

ORD record
ord-4345e6e1eae24fa9906d0a47740fb322
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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