6-Bromo-5-fluoroquinoline → (5-Fluoro-quinolin-6-yl)-acetic acid tert-butyl ester

HRID 655270Notes

Reaction equation

Br[C:2]1[C:3]([F:12])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[C:13]([O-:16])(=[O:15])[CH3:14].[Br-].[C:18]([Zn+2])([CH3:21])([CH3:20])[CH3:19]>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([O:15][C:13](=[O:16])[CH2:14][C:2]1[C:3]([F:12])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2)([CH3:21])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 6-bromo-5-fluoro-quinoline (1.0 g, 4.5 mmol) in tetrahydrofuran (1 mL) was added a solution of tert-butylzincbromide acetate (9 mmol, 20 mL, 10.4 M in tetrahydrofuran) followed by Pd(PPh3)4 (0.52 g, 0.45 mmol). The mixture was heated in a microwave reactor for 30 min at 120° C. The reaction mixture was quenched with a saturated ammonium chloride (60 mL), and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography to afford the title compound (0.83 g, 71%). 1H-NMR (CDCl3, 300 MHz): 8.9 (d, 1H), 8.4 (d, 1H), 7.8 (d, 1H), 7.6 (m, 1H), 7.5 (m, 1H), 3.7 (d, 2H), 1.4 (s, 9H).

Workup

customThe reaction mixture was quenched with a saturated ammonium chloride (60 mL)
extractionextracted with ethyl acetate
dry with materialThe organic layer was dried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-3905cbd81c434a1f89d8eeb2344d4642
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071581B2

Reaction notes

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