perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate → perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate

HRID 528528Notes

Reaction equation

HRID 528528 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([O:25][C:26]3[C:31]([F:32])=[C:30]([F:33])[C:29]([F:34])=[C:28]([F:35])[C:27]=3[F:36])(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.[C:37]([Zn]C#N)#[N:38]>>[C:37]([C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([O:25][C:26]3[C:31]([F:32])=[C:30]([F:33])[C:29]([F:34])=[C:28]([F:35])[C:27]=3[F:36])(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2)#[N:38]

Participants

3

Reactant 2

HCID 89761935perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonateHCID 178514179HCID 178514179, compound

Product 1

HCID 89762001perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonateYield 91.8%

Procedure

A round bottom flask was charged with perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (see EXAMPLE 46, STEP 1) (391 mg, 0.647 mmol), dicyanozinc (380 mg, 3.24 mmol), and palladum (0) bis(tri-tert-butylphosphine) (33.1 mg, 0.065 mmol). The flask was flushed with Ar (g), then DMAC (3235 μL) was added. A reflux condenser was attached, and the flask was lowered into a 60° C. heating bath overnight. The mixture was cooled to room temperature and diluted with water and EtOAc. A small portion of brine was added to break up an emulsion, and the layers were separated. The aq. layer was extracted with EtOAc (2×), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The product was purified by chromatography on silica gel (40 g, 0 to 30% EtOAc/Heptane) to give perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (327 mg, 0.594 mmol) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.50 (d, J=2.2 Hz, 1 H), 8.26-8.13 (m, 1 H), 7.85 (d, J=8.5 Hz, 1 H), 7.43 (d, J=2.2 Hz, 1 H), 7.33 (dd, J=2.3, 8.8 Hz, 1 H), 6.80 (d, J=8.8 Hz, 1 H), 4.45-4.40 (m, 2 H), 3.94 (t, J=4.2 Hz, 2 H). m/z (ESI) 573.2 (M+H)+.

Workup

  1. customThe flask was flushed with Ar (g)
  2. additionDMAC (3235 μL) was added
  3. customA reflux condenser was attached
  4. customwas lowered into a 60° C.
  5. temperatureheating bath overnight
  6. additiondiluted with water and EtOAc
  7. additionA small portion of brine was added
  8. customthe layers were separated
  9. extractionThe aq. layer was extracted with EtOAc (2×)
  10. dry with materialthe combined organic extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe product was purified by chromatography on silica gel (40 g, 0 to 30% EtOAc/Heptane)

Sources & evidence

ORD record
ord-a99e1fcfe5954334aec21925f4ce19f9
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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