Acetic Acid → Methyl (5R)-5-(5-{[(2-fluorophenyl)methyl]oxy}-2-pyridinyl)-L-prolinate

HRID 2264832Notes

Reaction equation

HRID 2264832 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH2:17][CH2:18][C@@H:19]([C:21]([O:23][CH3:24])=[O:22])[N:20]=2)=[N:14][CH:15]=1.C(O)(=O)C.FC(F)(F)C(O)=O>C(OCC)(=O)C.[Pt]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C@@H:16]2[NH:20][C@H:19]([C:21]([O:23][CH3:24])=[O:22])[CH2:18][CH2:17]2)=[N:14][CH:15]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 59596699Methyl (2S)-5-(5-{[(2-fluorophenyl)methyl]oxy}-2-pyridinyl)-3,4-dihydro-2H-pyrrole-2-carboxylate

Product 1

HCID 59596692Methyl (5R)-5-(5-{[(2-fluorophenyl)methyl]oxy}-2-pyridinyl)-L-prolinateYield 60%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl (2S)-5-(5-{[(2-fluorophenyl)methyl]oxy}-2-pyridinyl)-3,4-dihydro-2H-pyrrole-2-carboxylate (D85, 300 mg, 0.91 mmol) in ethyl acetate was added platinum on activated carbon (70 mg, 5 wt. % dry basis Degussa type F101 RAW) and the mixture was stirred under hydrogen atmosphere (P=1 atm) for 4 hours. After a further addiction of acetic acid (0.4 ml) and stirring for 12 hours the reaction wasn't complete. A further addiction of catalyst (70 mg) and trifluoroacetic acid was required before the reaction was complete. The catalyst was filtered off, the solvent removed under reduced pressure and the residue filtered on scx cartridge. The residue was purified by chromatography on silica gel using cyclohexane/ethyl acetate (7:3 to 6:4) to afford the title compound as a colourless oil (180 mg, 60%). Rt (HPLC): 3.69 min; MS: (ES/+) m/z: 331 [MH]+ C18H19FN2O3 requires 330; 1H NMR (400 MHz, CDCl3) δ (ppm): 8.27-8.43 (m, 1H); 7.45-7.56 (m, 1H); 7.38-7.44 (m, 1H); 7.31-7.38 (m, 1H); 7.24-7.31 (m, 1H); 7.15-7.23 (m, 1H); 7.08-7.15 (m, 1H); 5.18 (s, 2H); 4.32-4.41 (m, 1H); 3.98-4.05 (m, 1H); 3.79 (s, 3H); 2.19-2.31 (m, 2H); 2.04-2.13 (m, 1H); 1.77-1.90 (m, 1H).

Workup

  1. filtrationThe catalyst was filtered off
  2. customthe solvent removed under reduced pressure
  3. filtrationthe residue filtered on scx cartridge
  4. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-9c0a893f68924d1fb9574b2392269750
Source dataset
uspto-grants-2010_12
Patent number
US07855218B2

Reaction notes

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