Water → HCID 25009157, compound

HRID 2093210Notes

Reaction equation

HRID 2093210 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[Cl: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>C(Cl)Cl>[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[Cl: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

6

Reactant 4

HCID 962WaterHCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 57704785HCID 57704785, compound

Product 1

HCID 25009157HCID 25009157, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

methyl 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-chloro-6′-fluoro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (84.5 mg, 0.11 mmol), lithium hydroxide monohydrate (46.2 mg, 1.1 mmol), water (1 mL) and 1,4-dioxane (2 mL) were stirred at room temperature. LCMS of aliquot at reaction time was 2 hrs indicated completion of reaction. Volatiles were removed under reduced pressure. Crude mixture was dissolved in MeCN and acidified by HCl (1N, aq.) to afford a clear solution. This solution was purified by a 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. Corresponding fractions were pooled & evaporated in vacuo to afford a colorless glass. This glass was dissolved in DCM and washed with water. Organic extracts were combined, dried/Na2SO4, filtered and evaporated to afford the title compound. LCMS (ESI) calc.=749.10; found=750.06 (M+1)+. 1H NMR (CDCl3, 500 MHz, 1:1 mixture of atropisomers): δ 8.21 (dd, J=10, 2 Hz, 1H), 8.03 (dd, J=8, 2 Hz, 1H), 7.86 (s, 1H), 7.73-7.68 (m, 1.5H), 7.68-7.62 (m, 2.5H), 7.48 (t, J=7.5 Hz, 1H), 7.41 (dd, J=11, 8 Hz, 1H), 7.17 (dd, J=8.5, 2 Hz, 1H), 6.86 (dd, J=11, 3.5 Hz, 1H), 6.60 (d, J=8 Hz, 0.5H), 5.40 (d, J=8 Hz, 0.5H), 4.94 (t, J=15 Hz, 1H), 4.18 (d, J=16 Hz, 0.5H), 3.95 (d, J=16 Hz, 0.5H), 3.87 (s, 3H), 3.85-3.74 (m, 1H), 0.56 (d, J=6.5 Hz, 1.5H), 0.46 (d, J=6.5 Hz, 1.5H).

Workup

  1. customLCMS of aliquot at reaction time
  2. customcompletion of reaction
  3. customVolatiles were removed under reduced pressure
  4. dissolutionCrude mixture was dissolved in MeCN
  5. customto afford a clear solution
  6. customThis solution was purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  7. washeluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
  8. customevaporated in vacuo
  9. customto afford a colorless glass
  10. washwashed with water
  11. dry with materialdried/Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-4f24f0322f734327a5a588359ebf9054
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

Loading…