HCID 86627634, compound → HCID 24970055, compound

HRID 604660Notes

Reaction equation

HRID 604660 reaction equation
[F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][C:28]=3[C:29]3[CH:34]=[C:33]([CH:35]([CH3:37])[CH3:36])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[CH2:25][N:24](C(OCC3C=CC=CC=3)=O)[CH2:23]4)[C@H:14]2[CH3:51])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1>CC(O)=O.[Pd]>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][C:28]=3[C:29]3[CH:34]=[C:33]([CH:35]([CH3:36])[CH3:37])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[CH2:25][NH:24][CH2:23]4)[C@H:14]2[CH3:51])[CH:4]=[C:3]([C:2]([F:1])([F:52])[F:53])[CH:8]=1

Participants

4

Reactant 1

HCID 86627634HCID 86627634, compound

Product 1

HCID 24970055HCID 24970055, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of benzyl 5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(4-fluoro-5-isopropyl-2-methoxyphenyl)-1,3-dihydro-2H-isoindole-2-carboxylate (12 mg, 0.016 mmol) in AcOH (0.5 mL) was added a catalytic amount of Pd/C (10%). The mixture was stirred at room temperature under a H2 atmosphere for 2 h. The reaction mixture was filtered through Celite and the filtrate was adjusted to basic pH with sat. aq. NaHCO3. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were washed with brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (C-18), eluting with MeCN/water. The fractions were collected and lyophilized to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(4-fluoro-5-isopropyl-2-methoxyphenyl)-2,3-dihydro-1H-isoindol-5-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=611.2; found=610.8 (M+H)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers): δ 7.87 (s, 1H); 7.70 (s, 2H); 7.42 (s, 0.5H); 7.33 (s, 0.5H); 7.14 (s, 0.5H); 7.13 (s, 0.5H); 7.04 (d, J=8.5 Hz, 0.5H); 7.00 (d, J=8.5 Hz, 0.5H); 6.70 (d, J=5.4 Hz, 0.5H); 6.67 (d, J=5.3 Hz, 0.5H); 5.57 (d, J=8.1 Hz, 0.5H); 5.39 (d, J=8.0 Hz, 0.5H); 4.85 (d, J=15.4 Hz, 0.5H); 4.81 (d, J=15.5 Hz, 0.5H); 4.33 (s, 4H); 4.08 (d, J=15.4 Hz, 0.5H); 3.83 (d, J=15.4 Hz, 0.5H); 3.78 (s, 3H); 3.86-3.75 (m, 1H); 3.26-3.18 (m, 1H); 2.61 (br s, 1H); 1.31-1.25 (m, 4H); 1.19 (d, J=6.9 Hz, 2H); 0.52 (d, J=6.5 Hz, 1.5H); 0.34 (d, J=6.5 Hz, 1.5H).

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine (1×)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative reverse phase HPLC (C-18)
  8. washeluting with MeCN/water
  9. customThe fractions were collected

Sources & evidence

ORD record
ord-4d7399421061478fa4095b2b9d04fc3a
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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