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

HRID 245377Notes

Reaction equation

HRID 245377 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-bfe970af4ecd4fcb8826ea30fbf860c2
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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