Dimethylformamide → 1-Chloro-6-methoxy-3-methyl-isoquinoline-4-carbaldehyde

HRID 606312Notes

Reaction equation

[Li]CCCC.Br[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10]([Cl:19])=[N:9][C:8]=1[CH3:20].CN([CH:24]=[O:25])C>C1COCC1>[Cl:19][C:10]1[C:11]2[C:16](=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:7]([CH:24]=[O:25])=[C:8]([CH3:20])[N:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

n-BuLi (12 ml of 1.6 M in hexane) is added dropwise to a solution of 4-bromo-1-chloro-6-methoxy-3-methyl-isoquinoline (4.8 g, 17 mmol) in THF (60 ml) at −78° C. After stirring for 40 min, DMF (4 ml, 51 mmol) is added slowly. The reaction is allowed to warm to 0° C. and the stirring is continued for 1 h. The mixture is then quenched with 1N—HCl (30 ml) and extracted with EtOAc. The combined extracts are dried over Na2SO4 and evaporated. The residue is chromatographed on silica gel eluting with EtOAc/hexane (1:4) to give 2.9 g of 1-chloro-6-methoxy-3-methyl-isoquinoline-4-carbaldehyde. 1H NMR (CDCl3) 10.8 (s, 1H), 8.61 (s, 1H), 8.24 (d, 1H), 7.29 (d, 1H), 4.01 (s, 3H), 2.99 (s, 3H).

Workup

waitthe stirring is continued for 1 h
customThe mixture is then quenched with 1N—HCl (30 ml)
extractionextracted with EtOAc
dry with materialThe combined extracts are dried over Na2SO4
customevaporated
customThe residue is chromatographed on silica gel eluting with EtOAc/hexane (1:4)

Sources & evidence

ORD record: ord-430a20bdee074d54a2da199c33df1690
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915288B2

Reaction notes

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