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

HRID 2093171Notes

Reaction equation

HRID 2093171 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[O:13][C:12](=[O:14])[N:11]([CH2:15][C:16]3[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=3[C:26]3[CH:27]=[C:28]([C:34]4[CH:39]=[CH:38][C:37]([C:40]([O:42]C)=[O:41])=[CH:36][C:35]=4[CH3:44])[CH:29]=[CH:30][C:31]=3[O:32][CH3:33])[C@H:10]2[CH3:45])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[OH-].[K+].Cl.C(=O)(O)[O-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[O:13][C:12](=[O:14])[N:11]([CH2:15][C:16]3[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[CH:18][C:17]=3[C:26]3[CH:27]=[C:28]([C:34]4[CH:39]=[CH:38][C:37]([C:40]([OH:42])=[O:41])=[CH:36][C:35]=4[CH3:44])[CH:29]=[CH:30][C:31]=3[O:32][CH3:33])[C@H:10]2[CH3:45])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 25010403methyl 2''-{[(4S,5R)-5-(3,5-dichlorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 250079592''-{[(4S,5R)-5-(3,5-dichlorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 2″-{[(4S,5R)-5-(3,5-dichlorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (EXAMPLE 26) (50 mg, 0.076 mmol), aqueous potassium hydroxide (600 μL, 3M, 1.8 mmol) and ethanol (4 mL) were stirred at 20° C. for 6 hours. The reaction mixture was acidified by HCl (aq., 1N) and then basified by sodium bicarbonate. Volatiles were removed under reduced pressure. The resulting mixture was worked up with ethyl acetate, washed with brine. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to afford an oil. The oil was purified by preparative TLC (eluted with EtOAc/hexanes) to afford 2″-{[(4S,5R)-5-(3,5-dichlorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=643.11; found=644.14 (M+1)30. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 8.01 (d, J=5.5 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.70 (s, 1H), 7.65-7.61 (m, 1.5H), 7.44-7.37 (m, 3H), 7.34-7.31 (m, 1H), 7.29 (d, J=8.0 Hz, 0.5H), 7.29 (d, J=8.0 Hz, 0.5H), 7.27-7.24 (m, 0.5H), 7.14 (dd, J=7.0, 2.5 Hz, 1H), 7.09-7.03 (m, 1.5H), 7.00 (dd, J=8.25, 2.0 Hz, 1H), 5.42 (d, J=8.5 Hz, 0.55H), 5.17 (d, J=8.0 Hz, 0.45H), 4.92 (d, J=16.0 Hz, 0.55H), 4.86 (d, J=16.0 Hz, 0.45H), 4.18 (d, J=15.5 Hz, 0.55H), 3.96 (d, J=15.5 Hz, 0.45H), 3.86 (s, 3H), 3.75-3.66 (m, 1H), 2.38, 2.34 (s, 3H), 0.56 (d, J=6.5 Hz, 1.35H), 0.44 (d, J=6.5 Hz, 1.65H).

Workup

  1. customVolatiles were removed under reduced pressure
  2. washwashed with brine
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford an oil
  7. customThe oil was purified by preparative TLC (eluted with EtOAc/hexanes)

Sources & evidence

ORD record
ord-0391700f3b6d45cdbcd1f97dc5c97d83
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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