Hydrochloric Acid → HCID 16730182, compound

HRID 545591Notes

Reaction equation

HRID 545591 reaction equation
[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=1)[CH2:6][N:7]([CH2:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[C:23]1[CH:24]=[C:25]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([O:40]C)=[O:39])=[CH:34][C:33]=2[Cl:42])[C:26]([F:31])=[CH:27][C:28]=1[O:29][CH3:30])[C:8]([O:10][CH3:11])=[O:9].O.[OH-].[Li+].O.Cl>[Cl-].[Na+].O.O1CCOCC1>[F:49][C:46]([F:47])([F:48])[C:44]1[CH:43]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:50])[F:51])[CH:45]=1)[CH2:6][N:7]([CH2:12][C:13]1[CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=[CH:15][C:14]=1[C:23]1[CH:24]=[C:25]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([OH:40])=[O:39])=[CH:34][C:33]=2[Cl:42])[C:26]([F:31])=[CH:27][C:28]=1[O:29][CH3:30])[C:8]([O:10][CH3:11])=[O:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 16730183HCID 16730183, compound

Product 1

HCID 16730182HCID 16730182, compound

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Methyl 2″-{[[3,5-bis(trifluoromethyl)benzyl](methoxycarbonyl)amino]methyl}-2-chloro-6′-fluoro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′, 1″-terphenyl-4-carboxylate (34.7 mg, 0.0486 mmol), lithium hydroxide monohydrate (10 mg, 0.238 mmol), water (0.4 mL) and 1,4-dioxane (1 mL) were stirred at room temperature for 5.5 hours to complete the reaction. Crude mixture was acidified by HCl (aq, 1N, 6 mL). The resulting mixture was worked up with brine and extracted with ethyl acetate. The combined extracts were back-washed with water. The resulting organic layer was dried over Na2SO4, filtered and evaporated in vacuo to afford a clear oil. The resulting oil was purified on SiO2 to afford as a clear glass 2″-{[[3,5-bis(trifluoromethyl)benzyl](methoxycarbonyl)amino]methyl}-2-chloro-6′-fluoro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=699.17; found=700.29 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.95 (d, J=7.5 Hz, 1H), 7.72 (s, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.55-7.46 (m, 1.5H), 7.43-7.34 (m, 2.5H), 7.32-7.25 (m, 1H), 7.07-7.5 (m, 1H), 4.62-4.22 (m, 4H), 3.77 (s, 3H), 3.73 (d, J=17 Hz, 3H), 3.32 (s, 3H).

Workup

  1. customthe reaction
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were back-washed with water
  4. dry with materialThe resulting organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a clear oil
  8. customThe resulting oil was purified on SiO2

Sources & evidence

ORD record
ord-3a5714b2ae764bd39845ab287e629a01
Source dataset
uspto-grants-2011_05
Patent number
US07935727B2

Reaction notes

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