Methyl 2-bromobenzoate → Methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-oxopropyl)benzoate

HRID 865477Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([CH:20]([OH:23])[CH:21]=[CH2:22])[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1.[Li]OC(C)=O.[Li+].[Cl-].Br[C:32]1[CH:41]=[CH:40][CH:39]=[CH:38][C:33]=1[C:34]([O:36][CH3:37])=[O:35]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([C:20](=[O:23])[CH2:21][CH2:22][C:32]4[CH:41]=[CH:40][CH:39]=[CH:38][C:33]=4[C:34]([O:36][CH3:37])=[O:35])[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

A degassed suspension of 1-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-2-propen-1-ol (Example 80, Step 1, 50.30 g, 156 mmol), LiOAc/2H2O (41.2 g, 404 mmol), LiCl (6.84 g, 161 mmol), Pd(OAc)2 (1.00 g, 4.45 mmol ) and methyl 2-bromobenzoate (33.5 g, 156 mmol) in 300 mL of DMF was stirred at 95° C. for 4 h. The mixture was cooled to r.t (room temperature) and added to 1.8 L of water. The product was extracted with hot EtOAc, dried over Na2SO4 and concentrated. It was dissolved in toluene and filtered through silica with toluene. Recrystallization in 1.2 L of EtOAc:hexanes 1:1 afforded 65.57 g of the title compound. Recrystallization of the mother liquors in 400 mL EtOAc:hexanes 1:3 afforded a further 8.30 g (86% overall yield) of the title material.

Workup

temperatureThe mixture was cooled to r.t (room temperature)
extractionThe product was extracted with hot EtOAc
dry with materialdried over Na2SO4
concentrationconcentrated
dissolutionIt was dissolved in toluene
filtrationfiltered through silica with toluene
customRecrystallization in 1.2 L of EtOAc:hexanes 1:1

Sources & evidence

ORD record: ord-3ff280eb020d435aac24add2bebadf62
Source dataset: uspto-grants-1996_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05565473

Reaction notes

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