Reaktion #325923

Reaktionsgleichung

1-(3-bromophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine

9-BBN

ethyl hept-6-enoate

potassium phosphate

→

ethyl 7-(3-(1-amino-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)phenyl)heptanoate

Ausbeute 54.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cooling bath was removed
2. 2
   workup.STIRRINGstirred for an additional 5 min
3. 3
   Sonstigeprepared
4. 4
   TemperaturThe resulting yellow solution was heated
5. 5
   Temperaturunder reflux for 20 h
6. 6
   TemperaturThe reaction mixture was cooled
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   ExtraktionThe residue was extracted between water (10 mL) and ether (10 mL)
9. 9
   WaschenThe ether layer was washed twice with water
10. 10
    Trocknendried over Na2SO4
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigeThe residue was purified by silica gel flash chromatography (2% to 10% EtOAc in Heptane)

Vorschrift

To a solution of ethyl hept-6-enoate (156 mg, 1 mmol) in dry THF (4 mL) cooled in an ice water bath was added a solution of 9-BBN (0.5 M in THF, 2.0 mL, 1 mmol). The cooling bath was removed and the reaction mixture was stirred for 1 h at room temperature. To the reaction mixture was added an aqueous solution of potassium phosphate (3 M, 0.66 mL, 2 mmol) and stirred for an additional 5 min. To the reaction mixture was added a solution of 1-(3-bromophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine, prepared as described in Procedure 1, (0.2 M in THF, 3 mL, 0.6 mmol), followed by tris-(dibenzylideneacetone) dipalladium(0) (45 mg, 0.04 mmol). The resulting yellow solution was heated under reflux for 20 h. The reaction mixture was cooled and concentrated under reduced pressure. The residue was extracted between water (10 mL) and ether (10 mL). The ether layer was washed twice with water, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (2% to 10% EtOAc in Heptane) to yield ethyl 7-(3-(1-amino-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)phenyl)heptanoate (169 mg, 54% yield). LCMS: RT=3.61 min, Purity 84% [M+H] 516.3 (Sunfire-S5-C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm).

Quelle