Hydrochloric Acid → 4-{4-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-5-ethyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

HRID 607131Notes

Reaction equation

HRID 607131 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[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[N:31]=[C:32]([C:37]4[CH:46]=[CH:45][C:40]([C:41]([O:43]C)=[O:42])=[CH:39][C:38]=4[CH3:47])[S:33][C:34]=3[CH2:35][CH3:36])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Li+].[OH-].Cl>O1CCOCC1.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[CH:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:23]=[CH:22][C:21]=3[C:30]3[N:31]=[C:32]([C:37]4[CH:46]=[CH:45][C:40]([C:41]([OH:43])=[O:42])=[CH:39][C:38]=4[CH3:47])[S:33][C:34]=3[CH2:35][CH3:36])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 25010233methyl 4-{4-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-5-ethyl-1,3-thiazol-2-yl}-3-methylbenzoate

Product 1

HCID 250102344-{4-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-5-ethyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 4-{4-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-5-ethyl-1,3-thiazol-2-yl}-3-methylbenzoate (11 mg, 0.015 mmol) in 1,4-dioxane (0.4 mL) and water (0.4 mL), was added 1N LiOH (0.151 mL, 0.151 mmol). The mixture was stirred at room temperature for 2 h. The mixture was acidified with 1N HCl. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), filtered and the solvent was evaporated in vacuo. The residue was purified by preparative HPLC reverse phase (C-18), eluting with MeCN/water containing 0.1% TFA. The fractions were collected and lyophilized to give 4-{4-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-5-ethyl-1,3-thiazol-2-yl}-3-methylbenzoic acid. LCMS calc.=717.1; found=717.0 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H); 7.99 (d, J=8.1 Hz, 1H); 7.89 (d, J=8.1 Hz, 1H); 7.87 (s, 1H); 7.78 (s, 1H); 7.74 (d, J=8.0 Hz, 1H); 7.71 (s, 2H); 7.57 (d, J=7.9 Hz, 1H); 5.61 (d, J=8.0 Hz, 1H); 4.94 (d, J=15.7 Hz, 1H); 4.25 (d, J=15.7 Hz, 1H); 4.04-3.98 (m, 1H); 2.89-2.76 (m, 2H); 2.69 (s, 3H); 1.37 (t, J=7.5 Hz, 3H); 0.60 (d, J=6.5 Hz, 3H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. customthe solvent was evaporated in vacuo
  5. customThe residue was purified by preparative HPLC reverse phase (C-18)
  6. washeluting with MeCN/water containing 0.1% TFA
  7. customThe fractions were collected

Sources & evidence

ORD record
ord-06ff687c0ba04152b8a1c7cbb76ee97f
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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