Hydrochloric Acid → 3'-[2-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

HRID 604685Notes

Reaction equation

HRID 604685 reaction equation
[F:1][C:2]([F:50])([F:49])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42]C)=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:45]4[CH2:47][CH2:46]4)[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].O1CCOCC1.Cl>O>[F:50][C:2]([F:1])([F:49])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([OH:42])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:45]4[CH2:46][CH2:47]4)[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 86627637Methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

Product 1

HCID 249690113'-[2-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (70 mg, 0.100 mmol), lithium hydroxide monohydrate (21.02 mg, 0.501 mmol), 1,4-dioxane (1.670 mL) and water (1.670 mL) were stirred at room temperature. LCMS indicated about 8% conversion when reaction time was 1 h. LCMS trace of reaction aliquot at reaction time 18 h indicated completion of reaction. Reaction mixture was acidified by HCl (aq., 1N). Volatiles were removed under reduced pressure. The resulting pot residue was purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The resulting aqueous mixture was extracted with EtOAc, washed with water, dried (Na2SO4), filtered and concentrated to afford a light yellow solid as the titled compound. LCMS calc.=684.21; found=685.96 (M+1)+. 1H NMR (500 MHz, CDCl3, 2:1 mixture of atropisomers): δ 8.02-7.90 (m, 3H), 7.85 (s, 1H), 7.70 (s, 2H), 7.50-7.44 (m, 1H), 7.37-7.28 (m, 1.5H), 7.16-7.09 (m, 2.5H), 5.70 (d, J=7 Hz, 0.67H), 5.63 (d, J=7.5 Hz, 0.33), 5.02 (d, J=15-5 Hz, 0.5H), 4.72 (d, J=15.5 Hz, 0.5H), 4.59 (d, J=16 Hz, 0.5H), 4.46 (d, J=16 Hz, 0.5H), 4.44-4.36 (m, 0.67H), 4.14-4.22 (m, 0.33H), 3.92-3.84 (m, 3H), 2.71 (br s, 0.67H), 2.61 (br s, 0.33H), 2.39 (s, 2H), 2.35 (s, 1H), 2.51-1.40 (m, 2H), 1.15-1.10 (m, 2H), 0.74 (d, J=6.5 Hz, 2H), 0.65 (d, J=5.5 Hz, 1H).

Workup

  1. customabout 8% conversion when reaction time
  2. customLCMS trace of reaction aliquot
  3. customat reaction time 18 h
  4. customcompletion of reaction
  5. customReaction mixture
  6. customVolatiles were removed under reduced pressure
  7. customThe resulting pot residue was purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  8. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min)
  9. customevaporated in vacuo
  10. customto afford an aqueous mixture
  11. extractionThe resulting aqueous mixture was extracted with EtOAc
  12. washwashed with water
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-2baf1e03954b45ad95fe6901ff1bb042
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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