Chlorosulfonic acid → 4-(4-Cyano-2-Methoxyphenyl)-6-Fluoro-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonyl Chloride

HRID 528610ノート

反応式

HRID 528610 の反応式
[F:1][C:2]1[CH:21]=[CH:20][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=3[O:18][CH3:19])[C:4]=2[CH:3]=1.[Cl:22][S:23](O)(=[O:25])=[O:24]>C(Cl)Cl>[C:14]([C:13]1[CH:16]=[CH:17][C:10]([N:9]2[CH2:8][CH2:7][O:6][C:5]3[CH:20]=[C:21]([S:23]([Cl:22])(=[O:25])=[O:24])[C:2]([F:1])=[CH:3][C:4]2=3)=[C:11]([O:18][CH3:19])[CH:12]=1)#[N:15]

参加物

4

反応物 2

HCID 24638Chlorosulfonic acidHCID 897619874-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile

生成物 1

HCID 897618034-(4-Cyano-2-Methoxyphenyl)-6-Fluoro-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonyl Chloride

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-78 °C

実験手順

To a vial charged with 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile (0.234 g, 0.823 mmol) was added DCM (3.29 ml). The resulting solution was cooled to −78° C. and chlorosulfonic acid (0.137 ml, 2.058 mmol) was added faster than dropwise. After 30 min the mixture was warmed to 0° C. and the mixture was allowed to stir and warm to rt over 3 hr. LC-MS indicated conversion to the desired product mass (M+23). The reaction mixture was added to ice carefully and EtOAc was used to wash reaction vial. The resulting mixture was extracted with EtOAc (2×). The layers were separated and the cloudy aqueous phase was diluted with brine and extracted once more with EtOAc. The combined organics were dried with Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified with a 40 g silicycle HP column ramping EtOAc in heptane (0-50%) providing product 4-(4-cyano-2-methoxyphenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (0.093 g, 0.243 mmol, 29.5% yield) as a light yellow solid. m/z (ESI) 405.2 (M+Na)+.

後処理

  1. temperatureAfter 30 min the mixture was warmed to 0° C.
  2. temperaturewarm to rt over 3 hr

出典と根拠

ORDレコード
ord-7ed94cec860345058a93a67c663114c8
出典データセット
uspto-grants-2016_05
特許番号
US09346798B2

反応ノート

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