1,8-Diazabicyclo(5.4.0)undec-7-ene → Ethyl 6-bromo-1-[(4-methoxyphenyl)methyl]-4-oxoquinoline-3-carboxylate

HRID 1486918Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([CH:26]=1)[C:7]([C:9](=[CH:15][NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:8].C1CCN2C(=NCCC2)CC1>CC(C)=O>[Br:1][C:2]1[CH:26]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:16]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[CH:15]=[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:7]2=[O:8]

Participants

Conditions

Temperature: 20 °C

Procedure

On a larger scale, ethyl 2-(5-bromo-2-fluorobenzoyl)-3-[(4-methoxyphenyl)methylamino]prop-2-enoate (8434 g, (7730 g assumed active), 17.71 mol) was charged to the vessel with acetone (23.2 L) at 15° C. DBU (2.8 L, 18.72 mol) was added over 25 minutes with an observed exotherm from 18-23° C. over the addition. A precipitate formed after ˜25 minutes and the batch continued to exotherm reaching a maximum of 37° C. after 1 h. The reaction was stirred at 20° C. for 16.5 h at which point HPLC indicated consumption of starting material and 96.5% product. The resulting precipitate was collected by filtration washing with TBME (4×3.4 L). The solid was then dried under vacuum at 40° C. to give 6033 g of the desired material as a white solid (81.6% yield over 3 steps, 99.8% purity by HPLC). Analytical data was consistent with that obtained on previous batches.

Workup

customA precipitate formed after ˜25 minutes
customa maximum of 37° C.
customafter 1 h
customconsumption of starting material and 96.5% product
filtrationThe resulting precipitate was collected by filtration
washwashing with TBME (4×3.4 L)
customThe solid was then dried under vacuum at 40° C.

Sources & evidence

ORD record: ord-a169f5f3d87c4b689e03769a3b433bc7
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428503B2

Reaction notes

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