Sodium hydride → HCID 89761522, compound

HRID 528514

Reaction equation

HRID 528514 reaction equation
[O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2.[H-].[Na+].[Br:13][C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:15]=1F>CN(C=O)C>[Br:13][C:14]1[CH:19]=[C:18]([C:20]([F:21])([F:22])[F:23])[CH:17]=[CH:16][C:15]=1[N:4]1[CH2:5][CH2:6][O:1][C:2]2[CH:10]=[CH:9][CH:8]=[CH:7][C:3]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1442953-Bromo-4-fluorobenzotrifluorideHCID 5850963,4-Dihydro-2H-1,4-benzoxazine

Product 1

HCID 89761522HCID 89761522, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask under nitrogen, 3,4-dihydro-2H-benzo[b][1,4]oxazine (Tyger Scientific Inc., Ewing, N.J., 0.457 mL, 3.70 mmol) was dissolved in DMF (18.50 mL) and at room temperature, NaH (60% dispersion in mineral oil) (0.326 g, 8.14 mmol) was added, and the reaction was stirred for 15 minutes. 2-Bromo-1-fluoro-4-(trifluoromethyl)benzene (Alfa Aesar, Ward Hill, Mass., 0.790 mL, 5.55 mmol) was then added, and the reaction was stirred overnight at room temperature until complete conversion to the desired product. The reaction was then quenched with saturated aqueous ammonium chloride solution, and extracted with EtOAc (×2). The combined organics were washed with brine, dried over sodium sulfate, and concentrated to give material, which was purified via silica gel MPLC (Biotage Isolera One; PuriFlash HP, 15μ, 25 g (Biotage, Uppsala, Sweden)), eluting with 0 to 100% ethyl acetate in heptanes. Fractions containing clean product were collected and concentrated under a vacuum to yield 1.73 g of 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (INTERMEDIATE B) as an orange oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.62-3.69 (m, 2H) 4.28 (t, J=4.21 Hz, 2H) 6.30 (dd, J=7.87, 1.71 Hz, 1 H) 6.71 (dtd, J=18.67, 7.42, 7.42, 1.71 Hz, 2H) 6.85 (dd, J=7.78, 1.81 Hz, 1 H) 7.59 (d, J=8.41 Hz, 1 H) 7.81 (dd, J=8.41, 1.56 Hz, 1 H) 8.13 (d, J=1.66 Hz, 1 H). m/z (ESI) 357.0 (M+H)+.

Sources & evidence

ORD record
ord-6d4dedf5aa9d473eaeef10a167f33214
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Linked notes

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