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

HRID 1620896Notes

Reaction equation

HRID 1620896 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-5288cb0fd00049b0b3edbb3e2a787c1d
Source dataset
uspto-grants-2014_07
Patent number
US08772336B2

Reaction notes

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