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

HRID 528604

Reaktionsgleichung

Reaktionsgleichung von HRID 528604
[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]

Komponenten

4

Edukt 2

HCID 24638Chlorosulfonic acidHCID 89762070HCID 89762070, Verbindung

Produkt 1

HCID 897616984-(2-cyano-4-(trifluoromethyl)phenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chlorideAusbeute 74,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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)+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-6021fc6fd4694698a58c3dcab6c436e0
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346798B2

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