Ammonium Chloride → Ethyl 4-chloro-3-hydroxy-5-phenyl-2-(4-fluoro-2-trifluoromethylbenzoylamino)pent-4-enoate

HRID 506488Notes

Reaction equation

HRID 506488 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:7])=[C:4]([C:17]([F:20])([F:19])[F:18])[CH:3]=1.C([N-]C(C)C)(C)C.[Li+].Cl[C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[CH:32]=[CH:33][CH:34]=[O:35].[NH4+].[Cl-:41]>C1COCC1>[Cl:41][C:33](=[CH:32][C:31]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:30]=1)[CH:34]([OH:35])[CH:9]([NH:8][C:6](=[O:7])[C:5]1[CH:15]=[CH:16][C:2]([F:1])=[CH:3][C:4]=1[C:17]([F:18])([F:19])[F:20])[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 30140422-ChlorocinnamaldehydeHCID 59432157Ethyl (4-fluoro-2-trifluoromethylbenzoylamino)acetate

Product 1

HCID 72297221Ethyl 4-chloro-3-hydroxy-5-phenyl-2-(4-fluoro-2-trifluoromethylbenzoylamino)pent-4-enoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-75 °C

Procedure

At −75° C., 5.0 g (0.0170 mol) of ethyl (4-fluoro-2-trifluoromethylbenzoylamino)acetate dissolved in THF were added dropwise to 25.0 ml (0.050 mol) of a 2M solution of lithium diisopropylamide in THF. After 1 h at −75° C., 3.50 g (0.021 mol) of 2-chlorocinnamaldehyde dissolved in THF were added dropwise, and the mixture was stirred at −75° C. for 1 h. Saturated NH4Cl solution was added dropwise and the mixture was warmed to RT and extracted with CH2Cl2. The combined organic phases were washed and dried, and the solvent was removed. The residue was purified chromatographically (SiO2, cyclohexane/ethyl acetate). This gave 7.5 g (96% of theory) of the title compound as a colorless solid (diastereomer mixture) which was reacted further without further purification.

Workup

  1. additionwere added dropwise
  2. temperaturethe mixture was warmed to RT
  3. extractionextracted with CH2Cl2
  4. washThe combined organic phases were washed
  5. customdried
  6. customthe solvent was removed
  7. customThe residue was purified chromatographically (SiO2, cyclohexane/ethyl acetate)
  8. customThis gave 7.5 g (96% of theory) of the title compound as a colorless solid (diastereomer mixture) which was reacted further without further purification

Sources & evidence

ORD record
ord-c28b6902540445b687345a44a4ead64e
Source dataset
uspto-grants-2010_08
Patent number
US07786046B2

Reaction notes

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