Pyridine → HCID 58823001, compound

HRID 459259Notes

Reaction equation

HRID 459259 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=O.N1C=CC=CC=1.[CH3:20][O:21][C:22](=[O:52])[CH:23]([O:50][CH3:51])[CH:24]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:39][CH:38]=2)=[CH:28][C:27]=1[F:49])O>C(Cl)Cl>[CH3:20][O:21][C:22](=[O:52])[CH:23]([O:50][CH3:51])[CH2:24][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:39][CH:38]=2)=[CH:28][C:27]=1[F:49]

Participants

5

Reactant 3

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 58822644HCID 58822644, compound

Product 1

HCID 58823001HCID 58823001, compoundYield 22.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic anhydride (0.043 mL, 0.37 mmol) and pyridine (0.074 mL, 0.93 mmol) were added to a solution of 3-{4-[3-(biphenyl-4-yloxy)-propoxy]-2-fluoro-phenyl}-3-hydroxy-2-methoxy-propionic acid methyl ester (0.142 g, 0.31 mmol) in methylene chloride (1 mL) at 0° C. The resulting mixture was stirred for 4 hours at room temperature and was concentrated under vacuum. The residue was dissolved in ethyl acetate (50 mL) and 10% palladium on carbon (0.064 g) was added to the solution. The mixture was stirred under hydrogen pressure (5 atm) for 16 hours. The mixture was filtered through celite and concentrated under vacuum. The residue was purified by silica gel chromatography (silica gel, hexanes/ethyl acetate 4:1) to give 3-{4-[3-(biphenyl-4-yloxy)-propoxy]-2-fluoro-phenyl}-2-methoxy-propionic acid methyl ester as a white solid (30 mg, 22%). 1H NMR (200 MHz, CDCl3): 7.60–7.50 (m, 4H); 7.46–7.27 (m, 3H); 7.18–7.09 (m, 1H); 7.03–6.96 (m, 2H); 6.70–6.61 (m, 2H); 4.17 (dt, 4H, J=9.1, 6.2); 4.00 (dd, 1H, J=7.3, 5.9); 3.74 (s, 3H); 3.37 (s, 3H); 3.13–2.93 (m, 2H); 2.28 (qn, 2H, J=6.2).

Workup

  1. concentrationwas concentrated under vacuum
  2. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  3. addition10% palladium on carbon (0.064 g) was added to the solution
  4. stirringThe mixture was stirred under hydrogen pressure (5 atm) for 16 hours
  5. filtrationThe mixture was filtered through celite
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by silica gel chromatography (silica gel, hexanes/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-95f9379767de4697bd77936e016ebfbf
Source dataset
uspto-grants-2007_03
Patent number
US07192982B2

Reaction notes

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