Hydrochloric Acid → HCID 67386941, compound

HRID 1799045Notes

Reaction equation

HRID 1799045 reaction equation
[O:1]1[CH2:5][C:4](=[O:6])[NH:3][C:2]1=[O:7].[Li+].[Cl-].C([Li])(C)(C)C.CCCCC.[CH:20]([C:22]1[CH:40]=[CH:39][C:25]([O:26][C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30]([C:37]#[N:38])=[CH:29][CH:28]=2)=[C:24]([O:41][CH3:42])[CH:23]=1)=O.Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C1COCC1>[O:7]=[C:2]1[NH:3][C:4](=[O:6])[C:5](=[CH:20][C:22]2[CH:40]=[CH:39][C:25]([O:26][C:27]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:30]([C:37]#[N:38])=[CH:29][CH:28]=3)=[C:24]([O:41][CH3:42])[CH:23]=2)[O:1]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8003PentaneHCID 973892,4-OxazolidinedioneHCID 433294Lithium ChlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 51050036HCID 51050036, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 67386941HCID 67386941, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of oxazolidine-2,4-dione (50.5 mg, 0.50 mmol), LiCl (128 mg, 3.0 mmol) and anhydrous THF (5.0 mL) cooled to −78° C. was added dropwise 1.7 M tert-butyllithium solution in pentane (0.616 mL, 1.05 mmol). After stirring at −78° C. for 20 minutes, the reaction mixture was warmed to 0° C. for 5 minutes. The mixture was recooled to −78° C. and a solution of 4-(4-formyl-2-methoxy-phenoxy)-naphthalene-1-carbonitrile (Example 19a) was added dropwise. After stirring at −78° C. for 15 minutes, 1 N HCl (1.05 mL, 1.05 mol) was added dropwise. The reaction mixture was allowed to warm up to room temperature. After evaporation of most of the solvent, p-toluenesulfonic acid monohydrate (85 mg, 0.5 mmol) and toluene (25 mL) were added. The mixture was heated to reflux with a Dean-Stark trap for 5 hours. After removal of solvent, the residue was taken up with a mixture of DMF and methanol and purified on a preparative HPLC [Waters XTerra® Prep MS O8 OBD™ Column (5 μm, 30×50 mm) using a gradient mixture of 0.1% aqueous TFA and acetonitrile]. 1H NMR (400 Hz, DMSO-d6) δ 12.45 (s, 1H), 8.43 (d, 1H), 8.16 (s, 1H), 8.11 (d, 1H), 8.00 (d, 1H), 7.88 (t, 1H), 7.77 (t, 1H), 7.65 (d, 1H), 7.32 (d, 1H), 7.09 (s, 1H), 6.63 (d, 1H), 3.73 (s, 3H); LC/MS (m/z) [M+1]+ 386.9 (calculated for C22H14N2O6, 386.1).

Workup

  1. temperaturethe reaction mixture was warmed to 0° C. for 5 minutes
  2. customwas recooled to −78° C.
  3. stirringAfter stirring at −78° C. for 15 minutes
  4. temperatureto warm up to room temperature
  5. additionwere added
  6. temperatureThe mixture was heated
  7. temperatureto reflux with a Dean-Stark trap for 5 hours
  8. customAfter removal of solvent
  9. additionthe residue was taken up with a mixture of DMF and methanol
  10. custompurified on a preparative HPLC [Waters XTerra® Prep MS O8 OBD™ Column (5 μm, 30×50 mm)
  11. additiona gradient mixture of 0.1% aqueous TFA and acetonitrile]

Sources & evidence

ORD record
ord-c0c6e163e7af4172ba3c6c259ce24acf
Source dataset
uspto-grants-2013_01
Patent number
US08344009B2

Reaction notes

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