반응 #1796

반응 방정식

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

용매

THF

THF

반응 조건

후처리

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

실험 절차

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.

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