反应 #1796

反应方程式

methyl 5-fluoro-2-methoxy-4-hydroxybenzoic acid

triphenylphosphine

(S)-(-)-1-(4-pyridyl)-ethanol

→

methyl 5-fluoro-2-methoxy-4-[1-(S)-(4-pyridyl)ethoxy]benzoate

溶剂

THF

THF

反应条件

后处理

1. 1
   workup.ADDITIONTo this was added, dropwise over a period of 1 h
2. 2
   温度to warm to ambient temperature overnight
3. 3
   过滤The reaction was filtered
4. 4
   其他the solvent was removed under reduced pressure
5. 5
   其他The residue was chromatographed on a silica gel column
6. 6
   其他the solvent removed under reduced pressure
7. 7
   其他to afford
8. 8
   其他The residue was rechromatographed on a preparative HPLC
9. 9
   其他the solvent removed under reduced pressure

实验过程

A stirred solution of methyl 5-fluoro-2-methoxy-4-hydroxybenzoic acid (250 mg, 1.25 mmol, see Scheme II) in THF (15 mL) was treated with triphenylphosphine (494 mg, 1.88 mmol) and cooled to 0° C. under Argon. To this was added, dropwise over a period of 1 h, a solution of (S)-(-)-1-(4-pyridyl)-ethanol (232 mg, 1.88 mmol) and N,N'-diethylazodicarboxylate (300 μL, 1.88 mmol) in THF (5 mL). The reaction was allowed to warm to ambient temperature overnight with stirring. The reaction was filtered and the solvent was removed under reduced pressure. The residue was chromatographed on a silica gel column packed in 1:1 CH2Cl2 :EtOAc and elated with same. The appropriate fractions were combined and the solvent removed under reduced pressure to afford an impure mixture of 5-fluoro-2-methoxy-4-[1-(S)-(4-pyridyl)ethoxylbenzoate. The residue was rechromatographed on a preparative HPLC using a gradient of 95:5 to 5:95 water:acetonitrile (0.1% TFA added). The appropriate fractions were combined and the solvent removed under reduced pressure to afford the methyl 5-fluoro-2-methoxy-4-[1-(S)-(4-pyridyl)ethoxy]benzoate.

来源