Reaktion #57363

Reaktionsgleichung

NH4Cl

sodium bis(trimethylsilyl)amide

(3-benzyloxypropyl)triphenyl-phosphonium bromide

methyl 6-amino-4-(4-fluorophenyl)-5-formyl-2-(1-methylethyl)-3-pyridinecarboxylate

→

methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate

Ausbeute 82.0%

Lösungsmittel

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   workup.STIRRINGstirred for another 30 min
3. 3
   TemperaturThe mixture was then cooled to −78° C.
4. 4
   workup.STIRRINGThe resulting mixture was stirred at −78° C. for 30 min
5. 5
   Temperaturto warm to room temperature
6. 6
   workup.STIRRINGstirred for 2 h
7. 7
   Extraktionwas extracted with ethyl acetate
8. 8
   WaschenThe combined organic layers were washed with brine
9. 9
   Sonstigeevaporated
10. 10
    Sonstigeportion was purified by a silica gel chromatography (120 g column)
11. 11
    EinengenThe collected fractions were concentrated

Vorschrift

To a suspension of (3-benzyloxypropyl)triphenyl-phosphonium bromide (8.55 g, 17.4 mmol) in tetrahydrofuran (15 mL) was added dropwise sodium bis(trimethylsilyl)amide (34.8 mL, 1.0 M in tetrahydrofuran) under nitrogen at −78° C. The reaction was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for another 30 min. The mixture was then cooled to −78° C. and a solution of methyl 6-amino-4-(4-fluorophenyl)-5-formyl-2-(1-methylethyl)-3-pyridinecarboxylate (5.0 g, 15.8 mmol) in tetrahydrofuran (10 mL) was added dropwise over 45 min. The resulting mixture was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for 2 h. The resulting mixture was then poured into a mixture of ice, ethyl acetate, saturated aqueous NH4Cl and was extracted with ethyl acetate. The combined organic layers were washed with brine and evaporated. The residue was equally divided and portion was purified by a silica gel chromatography (120 g column), using 0% to 45% of ethyl acetate in hexanes. The collected fractions were concentrated to provide methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate as a light orange oil (5.79 g, 82%): LCMS (ESI, pos. ion spectrum) m/z 449 (M+H); HPLC (method 3) tR=3.2 min.

Quelle