Methanesulfonic Acid → 3-{4-[({2',6'-Dimethyl-4'-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)amino]-2-fluorophenyl}propanoic acid methanesulfonate

HRID 508073Notes

Reaction equation

HRID 508073 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:5]=[C:4]([CH3:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]([O:36]C(C)(C)C)=[O:35])=[C:28]([F:41])[CH:27]=2)[CH:19]=1.FC(F)(F)C(O)=O.[CH3:49][S:50]([OH:53])(=[O:52])=[O:51]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:49][S:50]([OH:53])(=[O:52])=[O:51].[CH3:17][C:4]1[CH:5]=[C:6]([O:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:7]=[C:2]([CH3:1])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[C:28]([F:41])[CH:27]=2)[CH:19]=1

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 23157580Tert-butyl 3-{4-[({2',6'-dimethyl-4'-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)amino]-2-fluorophenyl}propanoate

Product 1

HCID 866243823-{4-[({2',6'-Dimethyl-4'-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)amino]-2-fluorophenyl}propanoic acid methanesulfonateYield 88%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 3-{4-[({2′,6′-dimethyl-4′-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)amino]-2-fluorophenyl}propanoate (0.51 g, 0.91 mmol) in toluene (5 mL) was added trifluoroacetic acid (5 mL) under stirring at room temperature, and the mixture was stirred for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was neutralized with saturated aqueous sodium hydrogencarbonate. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1-ethyl acetate-ethyl acetate/methanol=10/1) to give a colorless amorphous powder. The obtained amorphous powder was dissolved in ethyl acetate, and methanesulfonic acid (0.82 mL) was added. The precipitated crystals were collected by filtration, washed, and dried to give the title compound (0.44 g, yield 88%) as colorless crystals.

Workup

  1. stirringthe mixture was stirred for 3 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1-ethyl acetate-ethyl acetate/methanol=10/1)
  7. customto give a colorless amorphous powder
  8. filtrationThe precipitated crystals were collected by filtration
  9. washwashed
  10. customdried

Sources & evidence

ORD record
ord-a301f974554b484e9c9d1be2b699d77b
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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