Acetic Acid → (4-Bromo-6-chloro-quinolin-2-yl)-(2-methoxy-benzyl)-amine

HRID 1949021Notes

Reaction equation

[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[C:4]([NH2:13])[CH:3]=1.[CH3:14][O:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH:18]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[C:4]([NH:13][CH2:18][C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[O:15][CH3:14])[CH:3]=1

Participants

Conditions

Temperature: 40 °C

Procedure

4-Bromo-6-chloro-quinolin-2-ylamine (3.12 g, 12 mmol) was dissolved in 100 mL 1,2-dichloroethane. 2-Methoxybenzaldehyde (1.98 g, 15 mmol) and acetic acid (2.91 g, 48 mmol) were added. The reaction mixture was stirred at 40° C. for 3 h. Sodium triacetoxy borohydride (5.99 g, 25 mmol) was added and stirring was continued at room temperature overnight. The reaction mixture was quenched by addition of 200 mL sat. sodiumbicarbonate solution. The mixture was extracted three times with dichloromethane (200 mL each). The organic phases ware pooled, dried with sodium sulfate, filtered and evaporated. The residue purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100:0->80:20 gradient). (4-Bromo-6-chloro-quinolin-2-yl)-(2-methoxy-benzyl)-amine was obtained as an off-white solid (2.2 g, 48%), MS: m/e=379.1 (M+H+).

Workup

stirringstirring
waitwas continued at room temperature overnight
customThe reaction mixture was quenched by addition of 200 mL sat. sodiumbicarbonate solution
extractionThe mixture was extracted three times with dichloromethane (200 mL each)
dry with materialdried with sodium sulfate
filtrationfiltered
customevaporated
customThe residue purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100:0->80:20 gradient)

Sources & evidence

ORD record: ord-47ca78fdd5c34dd3a0858b5eb7b6c360
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399674B2

Reaction notes

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