N-bromobutanimide → (S)-1-(5-Bromo-6-methoxypyridin-2-yl)pyrrolidin-3-ol

HRID 1054904Notes

Reaction equation

[CH3:1][O:2][C:3]1[N:8]=[C:7]([N:9]2[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10]2)[CH:6]=[CH:5][CH:4]=1.[Br:15]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[Br:15][C:4]1[CH:5]=[CH:6][C:7]([N:9]2[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10]2)=[N:8][C:3]=1[O:2][CH3:1]

Participants

Conditions

Temperature: 8 °C

Procedure

To a solution of (3S)-1-(6-methoxypyridin-2-yl)pyrrolidin-3-ol (1.6 g, 8.24 mmol) in chloroform (90 mL), was added N-bromosuccinimide (1.47 g, 8.24 mmol) at 0° C. with an ice bath. The reaction was allowed to stir at room temperature (8° C.) for 5 hour. TLC (petroleum ether/ethyl acetate) showed that the reaction was complete. The reaction mixture was evaporated to remove chloroform, dissolved in DCM (20 mL) and diluted with water (15 mL). The resulting mixture was separated and the aqueous phase was extracted with dichloromethane (25 mL*3). The combined organic phase was washed with brine, dried over sodium sulfate and evaporated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether, 0-25% to give the title compound (187 mg, 8.5%) as a yellow gum. 1H NMR (400 MHz, CDCl3) ppm 7.46 (d, 1 H) 5.77 (d, 1 H) 4.44-4.59 (m, 1 H) 3.92 (s, 3 H) 3.37-3.61 (m, 4 H) 1.96-2.24 (m, 3 H).

Workup

customThe reaction mixture was evaporated
customto remove chloroform
dissolutiondissolved in DCM (20 mL)
additiondiluted with water (15 mL)
customThe resulting mixture was separated
extractionthe aqueous phase was extracted with dichloromethane (25 mL*3)
washThe combined organic phase was washed with brine
dry with materialdried over sodium sulfate
customevaporated in vacuo
customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether, 0-25%

Sources & evidence

ORD record: ord-6c7a33351cd846989f615d196520051c
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394285B2

Reaction notes

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