تفاعل #57363

معادلة التفاعل

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

المردود 82.0%

المذيبات

ethyl acetate

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to room temperature
2. 2
   workup.STIRRINGstirred for another 30 min
3. 3
   درجة الحرارةThe mixture was then cooled to −78° C.
4. 4
   workup.STIRRINGThe resulting mixture was stirred at −78° C. for 30 min
5. 5
   درجة الحرارةto warm to room temperature
6. 6
   workup.STIRRINGstirred for 2 h
7. 7
   استخلاصwas extracted with ethyl acetate
8. 8
   غسيلThe combined organic layers were washed with brine
9. 9
   أخرىevaporated
10. 10
    أخرىportion was purified by a silica gel chromatography (120 g column)
11. 11
    تركيزThe collected fractions were concentrated

الإجراء التجريبي

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.

المصدر