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

HRID 528604노트

반응식

HRID 528604 반응식
[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]

참가 물질

4

반응물 2

HCID 24638Chlorosulfonic acidHCID 897620702-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)benzonitrile

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-6021fc6fd4694698a58c3dcab6c436e0
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346798B2

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