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

HRID 607092Notes

Reaction equation

HRID 607092 reaction equation
O1CCOCC1.[F:7][C:8]([F:56])([F:55])[C:9]1[CH:10]=[C:11]([CH:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:50]=1)[CH2:12][N:13]1[C@H:17]([CH3:18])[C@@H:16]([C:19]2[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=2[C:29]2[CH:30]=[C:31]([C:36]3[CH:41]=[CH:40][C:39]([C:42]([O:44]C)=[O:43])=[CH:38][C:37]=3[CH3:46])[CH:32]=[CH:33][C:34]=2[Cl:35])[O:15][C:14]1=[O:47].O.[OH-].[Li+].Cl>O>[F:56][C:8]([F:7])([F:55])[C:9]1[CH:10]=[C:11]([CH:48]=[C:49]([C:51]([F:53])([F:54])[F:52])[CH:50]=1)[CH2:12][N:13]1[C@H:17]([CH3:18])[C@@H:16]([C:19]2[CH:24]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:22]=[CH:21][C:20]=2[C:29]2[CH:30]=[C:31]([C:36]3[CH:41]=[CH:40][C:39]([C:42]([OH:44])=[O:43])=[CH:38][C:37]=3[CH3:46])[CH:32]=[CH:33][C:34]=2[Cl:35])[O:15][C:14]1=[O:47]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 86630546methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-chloro-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 866305472''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-chloro-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 1,4-dioxane solution (3 mL) of methyl 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-chloro-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (65 mg, 0.089 mmol) was added a solution of lithium hydroxide monohydrate (26 mg, 0.623 mmol) in water (1.2 mL). Aliquot at reaction time 2 hours indicated completion of reaction (atropisomers present). Crude mixture was acidified by HCl (aq, 1N, 1 mL). The cloudy precipitation was dissolved by MeCN (2 mL). The resulting solution was purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture affording 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-chloro-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=715.12; found=716.20 (M+1)+. 1H NMR signals are doubled because of atropoisomerism. 1H NMR

Workup

  1. customAliquot at reaction time 2 hours
  2. customcompletion of reaction (atropisomers present)
  3. customThe cloudy precipitation
  4. dissolutionwas dissolved by MeCN (2 mL)
  5. customThe resulting solution was purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  6. washeluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture

Sources & evidence

ORD record
ord-12166444870541f1a7dfa05c3b54820b
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

Loading…