Ethyl 4,4,4-trifluoroacetoacetate → HCID 87940055, compound

HRID 1242625Notes

Reaction equation

HRID 1242625 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[C:23]([C:27]([CH2:29][C:30](OCC)=[O:31])=[O:28])([F:26])([F:25])[F:24]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:30](=[O:31])[CH2:29][C:27](=[O:28])[C:23]([F:26])([F:25])[F:24])=[CH:19][CH:20]=2)=[CH:10][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 67793Ethyl 4,4,4-trifluoroacetoacetate2×HCID 14806250HCID 14806250, compound

Product 1

HCID 87940055HCID 87940055, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-15 °C

Procedure

A solution of [4-(4-aminobenzyl)phenyl]carbamic acid tert-butyl ester (1.26 g, 4.2 mmol) in PhMe (15 mL) was treated with a PhMe (10 mL) solution of CF3COCH2CO2Et (0.79 g, 4.3 mmol), before being heated under reflux for 1 h. More CF3COCH2CO2Et (0.40 g, 2.2 mmol) was added, & the mixture was heated under reflux for 1.5 h. The precipitate generated when the mixture was cooled to −15° C. was collected to give {4-[4-(4,4,4-trifluoro-3-oxobutyrylamino)benzyl]phenyl}carbamic acid tert-butyl ester (1.62 g, 90%): m/z (ES−)=435.3 [M−H]−. This compound (1.00 g, 2.3 mmol) was added portionwise with stirring to cold H2SO4 (5 mL) to generate a brown solution. This solution was heated at 90° C. for 1 h, then the cooled mixture was poured onto crushed ice. The aqueous phase was treated with solid NaOH until basic, & the mixture was extracted with Et2O (200 mL). The Et2O extracts were dried (MgSO4), concentrated to a small volume, & triturated with PE to furnish the title compound (0.66 g, 91%): δH ((CD3)2SO)=3.80 (s, 2H), 4.85 (s, 2H), 6.45 (d, 2H), 6.85 (d, 2H), 6.95 (s, 1H), 7.35 (d, 1H), 7.40–7.50 (m, 2H); m/z (ES+)=319.1

Workup

  1. temperaturebefore being heated
  2. temperatureunder reflux for 1 h
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 1.5 h
  5. customwas collected

Sources & evidence

ORD record
ord-bed3ad16f63d4477b4eb626eb90a71b6
Source dataset
uspto-grants-2006_10
Patent number
US07115745B2

Reaction notes

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