Hydrochloric Acid → 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

HRID 2093190Notes

Reaction equation

HRID 2093190 reaction equation
[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[C:23]2[CH:24]=[C:25]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([O:39]C)=[O:38])=[CH:33][C:32]=3[CH3:41])[CH:26]=[CH:27][C:28]=2[O:29][CH3:30])[O:9][C:8]1=[O:42].O.[OH-].[Li+].O.Cl>C(OCC)(=O)C.O1CCOCC1>[F:51][C:2]([F:1])([F:50])[C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([C:46]([F:47])([F:48])[F:49])[CH:45]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=[CH:15][C:14]=2[C:23]2[CH:24]=[C:25]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([OH:39])=[O:38])=[CH:33][C:32]=3[CH3:41])[CH:26]=[CH:27][C:28]=2[O:29][CH3:30])[O:9][C:8]1=[O:42]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86630542methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 866305432''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (21 mg, 0.029 mmol), lithium hydroxide monohydrate (9 mg, 0.21 mmol), water (0.4 mL) and 1,4-dioxane (1 mL) were stirred at 20° C. for 2 hours to complete the hydrolysis. The reaction mixture was acidified by HCl (aq., 1 mL). The resulting crude mixture was worked up with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to a clear oil. This oil was purified by a preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm) eluted with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. Related fractions were pooled and evaporated to afford 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=711.17; found=712.28 (M+1)+. 1H NMR signals are doubled because of atropoisomerism. 1H NMR (CDCl3, 500 MHz) δ 8.01 (s, 0.4H), 7.97 (s, 0.6H), 7.95 (d, J=7.0 Hz, 0.4H), 7.93 (d, J=6.5 Hz, 0.6H), 7.81 (s, 0.4H), 7.77 (s, 0.6H), 7.75 (s, 0.4H), 7.71 (s, 0.6H), 7.68 (d, J=6.5 Hz, 0.6H), 7.66 (d, J=6.5 Hz, 0.4H), 7.62 (s, 1H), 7.55 (s, 1H), 7.41-7.35 (m, 2H), 7.32 (d, J=6.5 Hz, 0.4H), 7.23 (d, J=6.5 Hz, 0.6H), 7.16 (d, J=2 Hz, 0.4H), 7.08 (d, J=7.5 Hz, 0.6H), 7.02 (d, J=7.5 Hz, 0.4H), 6.98 (d, J=2.0 Hz, 0.6H), 5.22 (d, J=4 Hz, 0.6H), 5.13 (d, J=4.5 Hz, 0.4H), 4.82, 4.75 (d, J=13.5 Hz, 1H), 4.29, 4.26 (d, J=15.5 Hz, 1H), 3.86 (s, 1.8H), 3.59 (s, 1.2H), 3.53-3.48 (m, 0.4H), 3.30-3.24 (m, 0.6H), 2.36, 2.22 (s, 3H), 0.89, 0.75 (d, J=5.5 Hz, 3H).

Workup

  1. customthe hydrolysis
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated to a clear oil
  5. customThis oil was purified by a preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm)
  6. washeluted with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
  7. customevaporated

Sources & evidence

ORD record
ord-fab25a1fc1984543aedf13adb90a640a
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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