Water → 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic Acid

HRID 607105Notes

Reaction equation

HRID 607105 reaction equation
[F:1][C:2]([F:52])([F:51])[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[CH:31]=[C:32]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([O:47]C)=[O:46])=[CH:41][C:40]=4[F:49])[C:33]([F:38])=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].O>O1CCOCC1>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[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:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([OH:47])=[O:46])=[CH:41][C:40]=4[F:49])[C:33]([F:38])=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:50])[CH:4]=[C:3]([C:2]([F:52])([F:51])[F:1])[CH:8]=1

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 57704789methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 250089942''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic Acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

methyl 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6′-difluoro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (50 mg, 0.067 mmol), lithium hydroxide monohydrate (28 mg, 0.67 mmol), water (1 mL) and 1,4-dioxane (2 mL) were stirred at room temperature for 2.5 hours. LCMS of aliquot indicated formation of the desired product and complete consumption of starting material. Crude mixture was acidified (1N HCl, aq.). Volatiles were removed under reduced pressure. Pot residue was dissolved in MeCN and purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting w/MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v). Corresponding fractions were pooled and evaporated in vacuo to afford a mixture. The resulting mixture was extracted with EtOAc. The separated organic phases were back washed w/water, separated, dried/Na2SO4, filtered and evaporated to afford the title compound. LCMS (ESI) calc.=733.13; found=734.14 (M+1)+. 1H NMR (CDCl3, 500 MHz, 1:1 mixture of atropisomers): δ 7.95 (t, J=6 Hz, 1H), 7.89-7.83 (m, 2H), 7.73 (s, 0.5H), 7.71 (s, 1H), 7.68-7.64 (m, 2H), 7.62 (s, 0.511) 7.58 (t, J=7 Hz, 0.5H), 7.53 (t, J=7.5 Hz, 0.5H), 7.42 (d, J=8 Hz, 0.5H), 7.39 (d, J=8 Hz, 0.5H), 7.31-7.23 (m, 1H), 6.89 (d, J=4 Hz, 0.5H), 6.87 (d, J=3.5 Hz, 0.5H), 5.61 (d, J=8 Hz, 0.5H), 5.29 (d, J=8 Hz, 0.5H), 5.05 (d, J=16 Hz, 0.5H), 4.93 (d, J=16 Hz, 0.5H), 4.16 (d, J=16.5 Hz, 0.5H), 3.94 (d, J=16 Hz, 0.5H), 3.89 (s, 1.5H), 3.87 (s, 1.5H), 3.85-3.72 (m, 1H), 0.59 (d, J=7 Hz, 1.5H), 0.43 (d, J=6 Hz, 1.5H).

Workup

  1. customLCMS of aliquot indicated formation of the desired product and complete consumption of starting material
  2. customVolatiles were removed under reduced pressure
  3. dissolutionPot residue was dissolved in MeCN
  4. custompurified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  5. washeluting w/MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v)
  6. customevaporated in vacuo
  7. customto afford a mixture
  8. extractionThe resulting mixture was extracted with EtOAc
  9. washThe separated organic phases were back washed w/water
  10. customseparated
  11. dry with materialdried/Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-52297764c1b04b8090ce34cc71b3c39b
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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