Bromine → (+/-)-9-Bromo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4-a-diaza-benzocyclohepten-4-one

HRID 1886964Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:17]=[C:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16][N:10]3[C:9](=[O:18])[CH:8]=2)=[N:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:29]Br>O1CCCC1>[Br:29][CH:12]1[C:11]2=[N:17][C:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)=[CH:8][C:9](=[O:18])[N:10]2[CH2:16][CH2:15][O:14][CH2:13]1

Participants

Conditions

Temperature: -40 °C

Procedure

To a solution of 5.00 g (20.47 mmol) of pyrimidin-4-yl-5,6,8,9-tetrahydro-7-oxa-1,4a-diaza-benzocyclohepten-4-one in dry tetrahydrofuran (200 mL) under argon at −40° C. was added 22.52 mL (22.52 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −40° C. for 10 min and 1.10 mL (21.49 mmol) of bromine was added rapidly. The reaction was stirred at −40° C. during 20 minutes and the reaction mixture was quenched with the addition of a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution and dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (cyclohexane/ethyl acetate: 80/20 to 70/30) to afford 2.18 g (33%) of product.

Workup

stirringThe reaction was stirred at −40° C. during 20 minutes
customthe reaction mixture was quenched with the addition of a saturated solution of ammonium chloride
extractionextracted with ethyl acetate
washThe organic phase was washed with saturated sodium chloride solution
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue was purified by flash chromatography (cyclohexane/ethyl acetate: 80/20 to 70/30)

Sources & evidence

ORD record: ord-5f049757adf3446a847167f91016f2a1
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501728B2

Reaction notes

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