1,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene) → Ethyl 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate

HRID 1952185Notes

Reaction equation

HRID 1952185 reaction equation
C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=1[NH:37][CH:38]=[C:39]([C:45](OCC)=[O:46])[C:40]([O:42][CH2:43][CH3:44])=[O:41]>>[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:34])([F:35])[F:36])=[C:29]2[C:28]=1[NH:37][CH:38]=[C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:45]2=[O:46]

Participants

3

Reactant 2

HCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)HCID 2797069Diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino)methylene)malonate

Product 1

HCID 13337379Ethyl 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylateYield 65%

Conditions

Temperature
260 °C

Procedure

A 3-neck, 1-L flask was charged with Dowtherm® (200 mL, 8 mL/g), which was degassed at 200° C. for 1 h. The solvent was heated to 260° C. and charged in portions over 10 min with diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino)methylene)malonate 14 (25 g, 0.07 mol). The resulting mixture was stirred at 260° C. for 6.5 hours (h) and the resulting ethanol byproduct removed by distillation. The mixture was allowed to slowly cool to 80° C. Hexane (150 mL) was slowly added over 30 minutes (min), followed by an additional 200 mL of hexane added in one portion. The slurry was stirred until it had reached room temperature. The solid was filtered, washed with hexane (3×150 mL), and then dried under vacuum to provide ethyl 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate 15 as a tan solid (13.9 g, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H), 8.39 (s, 1H), 8.06 (d, J=8.3 Hz, 1H), 7.81 (d, J=8.4 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 1.29 (t, J=7.1 Hz, 3H).

Workup

  1. customwas degassed at 200° C. for 1 h
  2. customthe resulting ethanol byproduct removed by distillation
  3. temperatureto slowly cool to 80° C
  4. additionHexane (150 mL) was slowly added over 30 minutes (min)
  5. additionadded in one portion
  6. stirringThe slurry was stirred until it
  7. customhad reached room temperature
  8. filtrationThe solid was filtered
  9. washwashed with hexane (3×150 mL)
  10. customdried under vacuum

Sources & evidence

ORD record
ord-5243002c7aa74e6f82492a4b7a250403
Source dataset
uspto-grants-2013_03
Patent number
US08404849B2

Reaction notes

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