Chlorosulfonic acid → 4-(2-cyano-4-(trifluoromethyl)phenyl)-8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride

HRID 528607Notes

Reaction equation

HRID 528607 reaction equation
[F:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][N:11]([C:12]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:13]=3[C:14]#[N:15])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:24][S:25](O)(=[O:27])=[O:26]>C(Cl)Cl>[C:14]([C:13]1[CH:16]=[C:17]([C:20]([F:23])([F:21])[F:22])[CH:18]=[CH:19][C:12]=1[N:11]1[CH2:10][CH2:9][O:8][C:7]2[C:2]([F:1])=[C:3]([S:25]([Cl:24])(=[O:27])=[O:26])[CH:4]=[CH:5][C:6]1=2)#[N:15]

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 897620162-(8-fluoro-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)benzonitrile

Product 1

HCID 897617434-(2-cyano-4-(trifluoromethyl)phenyl)-8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chlorideYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a vial charged with 2-(8-fluoro-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)benzonitrile (0.168 g, 0.521 mmol) was added DCM (2.085 ml). The resulting solution was cooled in an ice water bath prior to the addition of chlorosulfonic acid (0.139 ml, 2.085 mmol), faster than dropwise. After 30 mins the solution was added to ice water, and mixture was extracted 2× with EtOAc. 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)-8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (0.127 g, 0.302 mmol, 57.9% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.91-3.99 (m, 2 H) 4.52 (dd, J=5.14, 3.67 Hz, 2 H) 6.42 (dd, J=9.19, 1.66 Hz, 1 H) 7.34 (dd, J=9.19, 6.75 Hz, 1 H) 7.60 (d, J=8.51 Hz, 1 H) 7.95 (dd, J=8.56, 1.81 Hz, 1 H) 8.07 (d, J=2.15 Hz, 1 H). m/z (ESI) 443.1 (M+Na)+.

Workup

  1. temperatureThe resulting solution was cooled in an ice water bath
  2. extractionwas extracted 2× with EtOAc
  3. dry with materialThe combined organics were dried with Na2SO4
  4. filtrationfiltered
  5. customdried under reduced pressure
  6. customThe crude material was purified with a 25 g SNAP column

Sources & evidence

ORD record
ord-6b09b22decd0469393b06ff5a94429d2
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

Loading…