2,2,2-Trifluoroacetophenone → HCID 67298723, compound

HRID 1009233Notes

Reaction equation

HRID 1009233 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([CH2:7][CH:8]([CH3:10])[CH3:9])[NH2:6].[F:12][C:13]([F:23])([F:22])[C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=O.C(N(C(C)C)CC)(C)C.[BH3-]C#N.[Na+].[OH-].[Na+]>ClCCl.CO.Cl[Ti](Cl)(Cl)Cl>[F:12][C:13]([F:22])([F:23])[CH:14]([NH:6][C@H:5]([C:4]([O:3][CH3:2])=[O:11])[CH2:7][CH:8]([CH3:10])[CH3:9])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

9

Reactant 5

HCID 99052,2,2-TrifluoroacetophenoneHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2723695Leucine methyl ester hydrochlorideHCID 5003444Sodium cyanoborohydride

Product 1

HCID 67298723HCID 67298723, compound

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalyst2×HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of L-leucine methyl ester hydrochloride (975 mg, 5.37 mmol) in dichloromethane (30 mL) was added 2,2,2-trifluoroacetophenone (0.75 mL, 5.34 mmol) and diisopropylethylamine (3.5 mL, 20 mmol). TiCl4 (0.55 mL, 5.0 mmol) in 0.45 mL dichloromethane was added dropwise, and the mixture was stirred overnight. Additional TiCl4 (0.4 mL, 3.6 mmol) was then added and the mixture was stirred 3 h. A solution of NaCNBH3 (1050 mg, 16.7 mmol) in MeOH (20 mL) was added and the mixture was stirred 2 h. Poured into 1N NaOH and extracted with ethyl acetate (2×). The organic phase was washed with 1N NaOH and brine, then dried over MgSO4 and evaporated. Purification by ISCO column chromatography (gradient 30% to 90% ethyl acetate/hexanes) provided methyl N-(2,2,2-trifluoro-1-phenylethyl)-L-leucinate.

Workup

  1. stirringthe mixture was stirred 3 h
  2. stirringthe mixture was stirred 2 h
  3. extractionextracted with ethyl acetate (2×)
  4. washThe organic phase was washed with 1N NaOH and brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customPurification by ISCO column chromatography (gradient 30% to 90% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-981c23b65404481881066efbd344ba05
Source dataset
uspto-grants-2011_07
Patent number
US07973037B2

Reaction notes

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