Ethyl bromoacetate → Ethyl 2-((3-(1,3-dioxolan-2-yl)quinolin-6-yl)oxy)acetate

HRID 1499097Notes

Reaction equation

HRID 1499097 reaction equation
Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:14][CH3:15])[CH:8]=2)[N:3]=1.B(Br)(Br)Br.N1C2C(=[CH:25][C:26]([OH:30])=CC=2)C=CC=1.BrC[C:33]([O:35][CH2:36][CH3:37])=[O:34].C(=O)([O-])[O-].[Cs+].[Cs+]>ClCCl.CC(C)=O>[O:13]1[CH2:25][CH2:26][O:30][CH:12]1[C:11]1[CH:2]=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([O:14][CH2:15][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:6][CH:5]=2

Participants

8

Reactant 5

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 113746-HydroxyquinolineHCID 25134Boron tribromideHCID 6890792-Chloro-6-methoxyquinoline-3-carbaldehyde

Product 1

HCID 90117698Ethyl 2-((3-(1,3-dioxolan-2-yl)quinolin-6-yl)oxy)acetate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

The masked aldehyde 3-(1,3-dioxolan-2-yl)-quinolin-6-ol LPO 55016 was obtained via a similar method as for SSA 48104 from 2-chloro-6-hydroxyquinoline-3-carbaldehyde LPO 50188A. LPO 50188A itself was prepared by treatment of 2-chloro-6-methoxyquinoline-3-carbaldehyde by boron tribromide (BBr3) in dichloromethane. Finally quinolin-6-ol LPO 55016 was O-alkylated by treatment with ethyl 2-bromoacetate and cesium carbonate as a base in acetone for 2 hours at 85° C. to yield ethyl 2-((3-(1,3-dioxolan-2-yl)quinolin-6-yl)oxy)acetate LPO 55070A (reaction scheme 2). The masked aldehyde 3-(1,3-dioxolan-2-yl)-8-(trifluoromethyl)quinolin-5-ol LPO 50180C was prepared by radical trifluoromethylation of dioxolane TTA 46034 using a methodology developed by Langlois B. et al., Tetrahedron Lett., (32), 51, 7525-7528, 1991 and modified by Baran P. et al., PNAS, 108, 35, 14411-14415, 2011 (reaction scheme 2).

Sources & evidence

ORD record
ord-13861697832d437dbb599426cf171b50
Source dataset
uspto-grants-2015_12
Patent number
US09200016B2

Reaction notes

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