Cyanogen Bromide → (R)-4-(6-Bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

HRID 1752461Notes

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:17][S@@](C(C)(C)C)=O)([CH3:16])[C:9]([F:15])([F:14])[C:10]([OH:13])([CH3:12])[CH3:11])[C:5]([F:24])=[CH:4][CH:3]=1.[N:25]#[C:26]Br>C(O)C>[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:16])[C:9]([F:14])([F:15])[C:10]([CH3:11])([CH3:12])[O:13][C:26]([NH2:25])=[N:17]2)[C:5]([F:24])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of (R)-2-methyl-propane-2-sulfinic acid [(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-3-hydroxy-1,3-dimethyl-butyl]-amide (2.95 g, 6.84 mmol) and cyanogen bromide (2.24 g, 20.52 mmol) in dry ethanol (68 ml) was sealed with a glass stopper and heated at 85° C. for 9 hr. The reaction solution was evaporated in vacuo and the crude product was taken up with ethyl acetate and 2M aq. ammonia. The organic phase was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The crude product (2.74 g) was chromatographed over silica gel (toluene/ethyl acetate 6:4) to give the title compound as a colourless solid. 1.19 g (48.9% yield).

Workup

customThe reaction solution was evaporated in vacuo
washThe organic phase was washed with water and brine
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated
customThe crude product (2.74 g) was chromatographed over silica gel (toluene/ethyl acetate 6:4)

Sources & evidence

ORD record: ord-0297fbcf22fe41e0a60ce95174414990
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163011B2

Reaction notes

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