Tetrahydrofuran → 1-(6-Bromo-2-methylpyridin-3-yl)-2-oxopyrrolidin-3-yl acetate

HRID 705499

Reaction equation

Br[CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([CH3:14])=[N:9][C:10]([Br:13])=[CH:11][CH:12]=2)[C:3]1=[O:15].C1COCC1.[CH3:21][C:22]([O-:24])=[O:23].[K+]>C1OCCOCCOCCOCCOCCOC1.C(OCC)(=O)C>[C:22]([O:24][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([CH3:14])=[N:9][C:10]([Br:13])=[CH:11][CH:12]=2)[C:3]1=[O:15])(=[O:23])[CH3:21]

Participants

Conditions

Temperature: 70 °C

Procedure

A 500 mL round-bottom flask was charged with crude 3-bromo-1-(6-bromo-2-methylpyridin-3-yl)pyrrolidin-2-one from step A (18.5 g), THF (50 mL), 18-Crown-6 (576 mg, 2.18 mmol) and KOAc (12.84 g, 131 mmol). The mixture was heated at 70° C. under argon overnight. After cooling the reaction mixture to room temperature, ethyl acetate (50 mL) was added. The organic layer was separated and washed with water (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated to a dark solid, which was purified by flash chromatography (silica gel, 20-100% ethyl acetate/hexane) to give 1-(6-bromo-2-methylpyridin-3-yl)-2-oxopyrrolidin-3-yl acetate (8.9 g, 65% yield for two steps) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.38 (q, J=8.3 Hz, 3H), 5.43 (t, J=8.2 Hz, 1H), 3.47-4.03 (m, 3H), 2.62-2.90 (m, 1H), 2.38-2.56 (m, 4H), 2.06-2.32 (m, 5H); MS (ESI) 314 (M+H).

Workup

temperatureAfter cooling the reaction mixture to room temperature
customThe organic layer was separated
washwashed with water (50 mL), brine (50 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated to a dark solid, which
customwas purified by flash chromatography (silica gel, 20-100% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-e8ba83085ec043ac92cb45a36c825e95
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174965B2

Linked notes

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