Hydrochloric Acid → HCID 11510336, compound

HRID 1992950Notes

Reaction equation

HRID 1992950 reaction equation
[C:1]1([C:7]2[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]=2[O:21][C:22]2[CH:29]=[CH:28][C:25](C=O)=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:30]([OH:36])(=[O:35])[CH2:31][C:32](O)=O.Cl>N1C=CC=CC=1.N1CCCCC1>[C:1]1([C:7]2[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]=2[O:21][C:22]2[CH:23]=[CH:24][C:25](/[CH:32]=[CH:31]/[C:30]([OH:36])=[O:35])=[CH:28][CH:29]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 867Malonic AcidHCID 86087146HCID 86087146, compound

Product 1

HCID 11510336HCID 11510336, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 8082PiperidineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
85 °C

Procedure

4-{[2-Phenyl-3-(trifluoromethyl)-1-naphthalenyl]oxy}benzaldehyde (183) (92 mg, 0.24 mmol) was dissolved in pyridine (3 mL). To this solution was added malonic acid (74 mg, 0.70 mmol) and 1 drop of piperidine. The reaction mixture was heated at 85° C. overnight, cooled and poured into 5 N HCl (20 mL). The mixture was extracted with EtOAc. The combined organic extract was washed with 5 N HCl, water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a light brown viscous oil, which upon trituration with 1% MeOH in hexanes, yielded 83 mg (81%) of the title compound (184) as a white solid. mp 210-211° C. 1H NMR (400 MHz, CH3OH-d4): δ 6.28 (d, J=15.9 Hz, 1H), 6.56 (d, J=8.8 Hz, 2H), 7.10-7.30 (m, 5H), 7.37 (d, J=8.7 Hz, 2H), 7.53 (d, J=16.0 Hz, 1H), 7.60-7.72 (m, 2H), 7.89 (d, J=8.1 Hz, 1H), 8.16 (d, J=8.1 Hz, 1H), 8.36 (s, 1H). LCMS (APCI): m/z 435 (M+H)+, m/z 433 (M−H)−. Anal. Calc for C26H17F3O3.⅙H2O: C, 71.39; H, 3.99. Found: C, 71.50; H, 3.94.

Workup

  1. temperaturecooled
  2. extractionThe mixture was extracted with EtOAc
  3. extractionThe combined organic extract
  4. washwas washed with 5 N HCl, water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give the crude product as a light brown viscous oil, which upon trituration with 1% MeOH in hexanes

Sources & evidence

ORD record
ord-92bbec45015a47a3ac5eccf88f3e1ad2
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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