Hydrochloric Acid → 5-(Chloromethyl)-1,3-difluoro-2-(methylthio)benzene

HRID 1838503ノート

反応式

HRID 1838503 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH2:11]O)[CH:5]=[C:6]([F:10])[C:7]=1[S:8][CH3:9].CS([Cl:17])(=O)=O.C(N(C(C)C)CC)(C)C.Cl>ClCCl>[Cl:17][CH2:11][C:4]1[CH:5]=[C:6]([F:10])[C:7]([S:8][CH3:9])=[C:2]([F:1])[CH:3]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 22746033(3,5-Difluoro-4-(methylthio)phenyl)methanol

生成物 1

HCID 227457405-(Chloromethyl)-1,3-difluoro-2-(methylthio)benzene収率 95%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of [3,5-difluoro-4-(methylthio)-phenyl]-methanol (24.0 g, 0.126 mol) in dichloromethane (300 mL) cooled in an ice bath was added methanesulfonylchloride (16.9 g, 0.147 mol) in portions followed by diisopropyl-ethylamine in portions. The mixture was allowed to warm to room temperature, and stirred for 18 hours. 4-dimethyl-aminopyridine was added and the mixture was heated to reflux for 2 hours, cooled, and stirred at room temperature for 18 hours. The mixture was poured into dilute HCl and extracted with dichloromethane once (75 mL) after separating. The combined extracts were washed with dilute sodium chloride, dried using magnesium sulfate, and concentrated. Purification by silica gel chromatography using 5% ethyl acetate in hexanes gave 5-(chloromethyl)-1,3-difluoro-2-(methylthio)benzene as a clear colorless liquid (24.9 g, 95%). 1H NMR (CDCl3/400 MHz) 6.92-6.96 (m, 2H), 4.49 (s, 2H), 2.44 (s, 3H). HRMS m/z 207.9893 (M+, calcd 207.9925).

後処理

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperaturecooled
  4. stirringstirred at room temperature for 18 hours
  5. extractionextracted with dichloromethane once (75 mL)
  6. customafter separating
  7. washThe combined extracts were washed with dilute sodium chloride
  8. customdried
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography

出典と根拠

ORDレコード
ord-c652844a480b4fb4a1e392d8c923a93d
出典データセット
uspto-grants-2004_01
特許番号
US06673818B2

反応ノート

読み込み中…