Chlorosulfonic acid → 4-(2-cyano-4-(trifluoromethyl)phenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride

HRID 528604

反応式

HRID 528604 の反応式
[F:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:10]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:11]=3[C:12]#[N:13])[C:4]=2[CH:3]=1.[Cl:24][S:25](O)(=[O:27])=[O:26]>C(Cl)Cl>[C:12]([C:11]1[CH:14]=[C:15]([C:18]([F:20])([F:21])[F:19])[CH:16]=[CH:17][C:10]=1[N:9]1[CH2:8][CH2:7][O:6][C:5]2[CH:22]=[C:23]([S:25]([Cl:24])(=[O:27])=[O:26])[C:2]([F:1])=[CH:3][C:4]1=2)#[N:13]

参加物

4

反応物 2

HCID 24638Chlorosulfonic acidHCID 89762070HCID 89762070、化合物

生成物 1

HCID 897616984-(2-cyano-4-(trifluoromethyl)phenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride収率 74.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a vial charged with 2-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-5-(trifluoromethyl)benzonitrile (1.85 g, 5.74 mmol) was added DCM (23 mL). The resulting solution was cooled in an ice water bath prior to the addition of chlorosulfonic acid (1.526 ml, 22.96 mmol), faster than dropwise. After 30 min of stirring LC-MS of the resulting yellow/brown solution indicated desired product mass as the main mass (M+23) with consumption of starting material. The solution was added to ice water, and extracted 2× with DCM. The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The crude material was purified with a 25 g SNAP column ramping EtOAc in heptane (0-25%, then isocratic at 25%, 10% DCM throughout) providing product as a white foam 4-(2-cyano-4-(trifluoromethyl)phenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (1.80 g, 4.28 mmol, 74.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.87-3.94 (m, 2 H) 4.40-4.49 (m, 2 H) 6.37 (d, J=11.15 Hz, 1 H) 7.50 (d, J=6.46 Hz, 1 H) 7.64 (d, J=8.51 Hz, 1 H) 7.94-8.01 (m, 1 H) 8.09 (dd, J=1.57, 0.59 Hz, 1 H). m/z (ESI) 443.1 (M+Na)+.

後処理

  1. temperatureThe resulting solution was cooled in an ice water bath
  2. customdesired product mass as the main mass (M+23) with consumption of starting material
  3. additionThe solution was added to ice water
  4. extractionextracted 2× with DCM
  5. dry with materialThe combined organics were dried with Na2SO4
  6. filtrationfiltered
  7. customdried under reduced pressure
  8. customThe crude material was purified with a 25 g SNAP column

出典と根拠

ORDレコード
ord-6021fc6fd4694698a58c3dcab6c436e0
出典データセット
uspto-grants-2016_05
特許番号
US09346798B2

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