1,4-Dioxa-8-azaspiro(4.5)decane → 1-(5-Fluoroquinolin-8-yl)piperidin-4-one

HRID 2242010Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.O1[C:17]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[O:16]CC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCCC1>[F:12][C:5]1[CH:4]=[CH:3][C:2]([N:20]2[CH2:21][CH2:22][C:17](=[O:16])[CH2:18][CH2:19]2)=[C:11]2[C:6]=1[CH:7]=[CH:8][CH:9]=[N:10]2

Participants

Conditions

Temperature: 66 °C

Procedure

To a 2-L reactor with a stirrer, a thermocouple, a condenser and nitrogen inlet were charged 8-bromo-5fluoroquinoline (50 g), tetrahydrofuran (795 g), Pd2(dba)3 (3.78 g), Cymap (1.6 g), and 1,4-Dioxa-8-azaspiro[4.5]decane (47.3 g). the mixture was heated to reflux (66° C.) and the reaction was complete. The reaction mixture was quenched into a 5 L reactor containing 1000 g of water and 640 g of MTBE. The bottom aqueous layer was split off and the organic layer was washed with 5% NaOH (1120 g) and 20% NaCl (2×100 g). The solvent was evaporated, weight 87 g vs 79.4 g by theory.

Workup

temperaturethe mixture was heated
customThe reaction mixture was quenched into a 5 L reactor
additioncontaining 1000 g of water and 640 g of MTBE
customThe bottom aqueous layer was split off
washthe organic layer was washed with 5% NaOH (1120 g) and 20% NaCl (2×100 g)
customThe solvent was evaporated

Sources & evidence

ORD record: ord-0d460ed6d61c44a69675e58821272a43
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07671056B2

Reaction notes

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