Hydrochloric Acid → HCID 87255948, compound

HRID 2093193Notes

Reaction equation

HRID 2093193 reaction equation
O1CCOCC1.[F:7][C:8]([F:57])([F:56])[C:9]1[CH:10]=[C:11]([CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:51]=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:37]3[CH:42]=[CH:41][C:40]([C:43]([O:45]C)=[O:44])=[CH:39][C:38]=3[Cl:47])[CH:32]=[CH:33][C:34]=2[O:35][CH3:36])[O:15][C:14]1=[O:48].O.[OH-].[Li+].Cl>O.ClCCl>[F:57][C:8]([F:7])([F:56])[C:9]1[CH:10]=[C:11]([CH:49]=[C:50]([C:52]([F:54])([F:55])[F:53])[CH:51]=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:37]3[CH:42]=[CH:41][C:40]([C:43]([OH:45])=[O:44])=[CH:39][C:38]=3[Cl:47])[CH:32]=[CH:33][C:34]=2[O:35][CH3:36])[O:15][C:14]1=[O:48]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 87255961HCID 87255961, compound

Product 1

HCID 87255948HCID 87255948, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 1,4-dioxane solution (2 mL) of starting methyl 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-2-chloro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (65 mg, 0.087 mmol) was added a solution of lithium hydroxide monohydrate (36.5 mg, 0.87 mmol) in water (1 mL). The resulting mixture turned to a cloudy, slightly purple mixture (from a light yellow solution). Aliquot at reaction time=22 min indicated completion of reaction. Reaction crude was acidified (1N HCl, aq.). Volatiles were removed from the crude mixture. The resulting mixture was purified by a preparative reverse phase 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. Related fractions were pooled & evaporated in vacuo to afford a colorless glass. The glass was dissolved in dichloromethane and washed with water. The organic layer was separated, dried over Na2SO4, filtered and concentrated in vacuo to afford 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-2-chloro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=731.11; found=732.08 (M+1)+. 1H NMR signals are doubled because of atropoisomerism. 1H NMR (CDCl3, 500 MHz) 8.22, 8.13 (d, J=1.5 Hz, 1H), 8.05-7.99 (m, 1H), 7.79 (s, 1H), 7.74 (s, 1H), 7.70-7.64 (m, 1H), 7.60 (s, 0.6H), 7.54-7.51 (m, 1.8H), 7.50-7.44 (m, 1H), 7.42-7.30 (m, 2H), 7.13 (d, J=2.5 Hz, 0.6H), 7.10 (d, J=9.0 Hz, 0.6H), 7.17 (d, J=8.5 Hz, 0.4H), 5.22 (d, J=4.5 Hz, 1H), 4.82, 4.77 (d, J=16 Hz, 1H), 4.27, 4.22 (d, J=16 Hz, 1H), 3.87 (s, 1.8H), 3.59 (s, 1.2H), 3.49-3.43 (m, 0.4H), 3.32-3.25 (m, 0.6H), 0.86 (d, J=6.0 Hz, 1.2H), 0.73 (d, J=6.5 Hz, 1.8H).

Workup

  1. customAliquot at reaction time=22 min
  2. customcompletion of reaction
  3. customReaction crude
  4. customVolatiles were removed from the crude mixture
  5. customThe resulting mixture was purified by a preparative reverse phase 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
  7. customevaporated in vacuo
  8. customto afford a colorless glass
  9. washwashed with water
  10. customThe organic layer was separated
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8fee7d0a2c6e4a95ba1c63900b6ab5ed
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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