benzyl 5-[2'-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylate → 5-[2'-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylic acid

HRID 2093177Notes

Reaction equation

HRID 2093177 reaction equation
[F:1][C:2]([F:57])([F:56])[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:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[C:32]([C:38]4[CH:39]=[CH:40][C:41]([C:45]([O:47]CC5C=CC=CC=5)=[O:46])=[N:42][C:43]=4[CH3:44])[CH:31]=3)[C@H:14]2[CH3:55])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1>C(O)C.[Pd]>[F:57][C:2]([F:1])([F:56])[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:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:23]=[CH:22][C:21]=3[C:30]3[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[C:32]([C:38]4[CH:39]=[CH:40][C:41]([C:45]([OH:47])=[O:46])=[N:42][C:43]=4[CH3:44])[CH:31]=3)[C@H:14]2[CH3:55])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 1

HCID 57704838benzyl 5-[2'-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylate

Product 1

HCID 250081275-[2'-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Benzyl 5-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylate (52 mg, 0.065 mmol), palladium/active carbon (10%, w/w) (25 mg) were mixed in ethanol (10 mL). The resulting mixture was degassed and subject to H2 under 45 psi at room temperature on a Parr shaker for 3 hours to complete the reaction. The reaction mixture was filtered through a pad of Celite (521). The filtrate was concentrated in vacuo to afford a light brown glass. The residue was purified by preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN/H2O gradient mixture. The appropriate fractions were pooled and evaporated into an aqueous residue. The resulting residue was further lyophilized to afford 5-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylic acid. LCMS calc.=712.16; found=713.19 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 8.07 (s, 1H), 7.86 (s, 1H), 7.77 (s, 1H), 7.71-7.62 (m, 4H), 7.45-7.36 (m, 2H), 7.19-7.07 (m, 2H), 5.55 (d, J=7.0 Hz, 0.55H), 5.42 (d, J=7 Hz, 0.45H), 4.99 (d, J=13 Hz, 0.5H), 4.85 (d, J=12.5 Hz, 0.5H), 4.14 (d, J=13.5 Hz, 0.5H), 3.95 (d, J=13.5 Hz, 0.5H), 3.92-3.80 (m, 4H), 2.61, 2.58 (s, 3H), 0.58 (d, J=5.0 Hz, 1.35H), 0.49 (d, J=5.5 Hz, 1.65H).

Workup

  1. customThe resulting mixture was degassed
  2. customthe reaction
  3. filtrationThe reaction mixture was filtered through a pad of Celite (521)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto afford a light brown glass
  6. customThe residue was purified by preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm)
  7. washeluting with a MeCN/H2O gradient mixture
  8. customevaporated into an aqueous residue

Sources & evidence

ORD record
ord-20ded594c5b549bda13c13ee8eeb890f
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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