Sodium Hydroxide → Tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-bromobenzoate

HRID 888419Notes

Reaction equation

HRID 888419 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15](=O)[C:16]([F:19])([F:18])[F:17])[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].C[Si]([N-:25][Si](C)(C)C)(C)C.[Li+].CSC.B.[OH-].[Na+]>C1(C)C=CC=CC=1>[NH2:25][CH:15]([C:13]1[CH:12]=[C:4]([CH:3]=[C:2]([Br:1])[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[C:16]([F:19])([F:18])[F:17]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 2733832Lithium HexamethyldisilazideHCID 12423031(Dimethyl sulfide)trihydroboronHCID 68496903tert-Butyl 3-bromo-5-(trifluoroacetyl)benzoate2×

Product 1

HCID 59539695Tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-bromobenzoateYield 49.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of tert-butyl 3-bromo-5-(trifluoroacetyl)benzoate (3.0 g, 8.5 mmol) in toluene (mL) was slowly added lithium bis(trimethylsilyl)amide (1.0 M in toluene; 25.5 mL, 25.5 mmol). The reaction was stirred at ambient temperature. After 1 h, the reaction was checked by TLC for disappearance of tert-butyl 3-bromo-5-(trifluoroacetyl)benzoate. Borane dimethyl sulfide complex (2.0 M in toluene; 25.5 mL, 51.0 mmol) was added and the mixture was stirred at ambient temperature. After 1 h, aqueous NaOH (1.0 M) was added slowly to quench the reaction. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate) gave the title compound (1.48 g).

Workup

  1. stirringthe mixture was stirred at ambient temperature
  2. waitAfter 1 h
  3. customto quench
  4. customthe reaction
  5. extractionThe mixture was extracted with ethyl acetate (3×)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-3c05b211b92d4e7abd9882b8fe530b92
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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