反応 #43783

反応方程式

161

7-{4-[2-(N-Benzyl-N-methylamino)-1-chloroethylidene]piperidin-1-yl}-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid trifluoroacetic acid salt

1-chloroethyl chloroformate

→

72

収率 27.3%

7-[4-(1-Chloro-2-methylaminoethylidene)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid trifluoroacetic acid salt

収率 27.3%

溶媒

1,2-dichloroethane

反応条件

後処理

1. 1
   温度the reaction mixture was warmed
2. 2
   温度to reflux temperature
3. 3
   濃縮it was concentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (5 mL)
5. 5
   workup.ADDITIONadjusted to pH>7 by the addition of NaHCO3 and water at room temperature
6. 6
   workup.STIRRINGstirred overnight
7. 7
   濃縮The resulting mixture was concentrated in vacuo
8. 8
   その他the residue purified by HPLC (reverse phase C-18 column, 35-90% acetonitrile/water containing 0.1% trifluoroacetic acid)

実験手順

A solution of 161 (160 mg, 0.24 mmol) was dissolved in 1,2-dichloroethane (4 mL) and was treated with 1-chloroethyl chloroformate (0.8 mL, 7.3 mmol) under nitrogen. After 5 min, the reaction mixture was warmed to reflux temperature and the reaction mixture was allowed to stir for 3 h. The resulting mixture was allowed to cool to room temperature, and then it was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (5 mL), adjusted to pH>7 by the addition of NaHCO3 and water at room temperature and stirred overnight. The resulting mixture was concentrated in vacuo and the residue purified by HPLC (reverse phase C-18 column, 35-90% acetonitrile/water containing 0.1% trifluoroacetic acid) to afford the trifluoroacetic acid salt of 72 (37 mg, 27%) as a yellow solid. MS 450 (M+H).

出典