Nitrogen → 4-Allyl-7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine

HRID 1400701Notes

Reaction equation

[F:1][C:2]1[C:3]([B:12]2[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]2)=[CH:4][C:5]2[NH:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.C([O-])([O-])=O.[K+].[K+].N#N.[CH2:29](Br)[CH:30]=[CH2:31]>CN(C=O)C.O>[CH2:31]([N:10]1[CH2:9][CH2:8][O:7][C:6]2[CH:11]=[C:2]([F:1])[C:3]([B:12]3[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]3)=[CH:4][C:5]1=2)[CH:30]=[CH2:29]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.503 g, 1.802 mmol, Ref. WO20100130034) and K2CO3 (0.504 g, 3.65 mmol) in dry DMF (5 mL) was sparged with N2 for 5 min, then treated with allyl bromide (0.8 mL, 9.17 mmol). The reaction tube was sealed then heated (70° C.) for 22 h. The reaction was diluted with water (50 mL) and extracted into EtOAc (50 mL). The organic layer was washed with water, brine, and then dried (Na2SO4), filtered, and concentrated. The residue was purified by biotage (4 g SiO2, 5% (3 CV), 5-40% (15 CV), 40% (2 CV), EtOAc in hexanes), affording the desired product (0.430 g, 1.347 mmol, 74.8% yield) as a clear viscous oil. 1H NMR (500 MHz, CDCl3) δ 7.03 (6, J=5.7 Hz, 1H), 6.51 (d, J=9.9 Hz, 1H), 5.84-5.94 (m, 1H), 5.26-5.31 (m, 1H), 5.24 (m, 1H), 4.25-4.32 (m, 2H), 3.87 (m, 2H), 3.19-3.25 (m, 2H), 1.34 (s, 12H). LCMS (M+H)=319.7.

Workup

customThe reaction tube was sealed
extractionextracted into EtOAc (50 mL)
washThe organic layer was washed with water, brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by biotage (4 g SiO2, 5% (3 CV), 5-40% (15 CV), 40% (2 CV), EtOAc in hexanes)

Sources & evidence

ORD record: ord-db5efb35a7d24d1a91856d4ab85c911e
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906929B2

Reaction notes

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