Hydrochloric Acid → HCID 25010574, compound

HRID 2093168Notes

Reaction equation

HRID 2093168 reaction equation
[F:1][C:2]([F:50])([F:49])[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:38]4[C:39]([C:44]([O:46]C)=[O:45])=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:33]=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+].O.Cl>C(O)C>[F:50][C:2]([F:1])([F:49])[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:38]4[C:39]([C:44]([OH:46])=[O:45])=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:33]=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14797Potassium HydroxideHCID 86630537HCID 86630537, compound

Product 1

HCID 25010574HCID 25010574, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-2-carboxylate (50 mg, 0.07 mmol), aqueous potassium hydroxide (1.1 mL, 3M, 3.3 mmol), water (1.5 mL) and ethanol (3.6 mL) were stirred at 20° C. for 23 hours. The reaction mixture was acidified by HCl (aq., 1N). Volatiles were removed under reduced pressure. The resulting mixture was worked up with ethyl acetate, washed with brine. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to an oil. This oil was purified by a reverse-phase preparative HPLC (column: Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN (0.1% v/v TFA buffered)/H2O (0.1% v/v TFA buffered) gradient mixture to afford 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-2-carboxylic acid. LCMS calc.=697.15; found=698.16 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 7.94 (t, J=7.0 Hz, 1H), 7.85 (d, J=7.0 Hz, 1H), 7.68-7.63 (m, 2.5H), 7.63-7.59 (m, 1.5H), 7.59-7.54 (m, 1H), 7.47-7.35 (m, 4H), 7.14 (dd, J=8.0, 2.0 Hz, 1H), 7.04 (d, J=8.5 Hz, 1H), 5.53 (d, J=8.0 Hz, 0.4H), 5.42 (d, J=8.0 Hz, 0.6H), 5.02 (d, J=15.5 Hz, 0.6H), 4.85 (d, J=15.5 Hz, 0.4H), 4.11-4.02 (m, 0.4H), 3.87-3.77 (m, 3.6H), 0.99 (d, J=6.5 Hz, 0.6H), 0.93 (d, J=7.0 Hz, 0.4H), 0.58 (d, J=7.0 Hz, 1.2H), 0.54 (d, J=6.5 Hz, 1.8H).

Workup

  1. customVolatiles were removed under reduced pressure
  2. washwashed with brine
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. customThis oil was purified by a reverse-phase preparative HPLC (column: Kromasil 100-5C18, 100×21.1 mm)
  7. washeluting with a MeCN (0.1% v/v TFA buffered)/H2O (0.1% v/v TFA buffered) gradient mixture

Sources & evidence

ORD record
ord-bc172a17da934a0d849f6848762820f6
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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