N,N-Dimethylglycine → 3-(5-Formyl-2-methoxy-phenoxy)-benzonitrile

HRID 332578Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6].I[C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[C:16]#[N:17].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O>[Cu]I.O1CCOCC1>[CH:5]([C:4]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:2]([CH:3]=1)[O:1][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[C:16]#[N:17])=[O:6]

Participants

Conditions

Temperature: 100 °C

Procedure

In a 350 mL pressure vessel equipped with a stir bar was placed 3-hydroxy-4-methoxy-benzaldehyde (15) (1.5 g, 9.86 mmol), 3-iodo-benzonitrile (3.39 g, 14.8 mmol), cesium carbonate (3.21 g, 9.86 mmol), N,N-dimethylglycine (275 mg, 1.97 mmol), copper(I) iodide (188 mg, 0.986 mmol) and 1,4-dioxane (55 mL). The mixture was heated to 100° C. for 46 hours. The reaction was cooled to room temperature, quenched with water (300 mL) and then extracted with ethyl acetate (3×200 mL). The organic portions were combined, washed with brine (300 mL), dried (MgSO4) and concentrated. The crude material was purified by silica gel column chromatography utilizing 35%, 50%, 75% ethyl acetate/hexanes to produce 1.09 g (42% yield) of (16) as a white solid.

Workup

customIn a 350 mL pressure vessel equipped with a stir bar
temperatureThe reaction was cooled to room temperature
customquenched with water (300 mL)
extractionextracted with ethyl acetate (3×200 mL)
washwashed with brine (300 mL)
dry with materialdried (MgSO4)
concentrationconcentrated
customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-7a2fe04db1af45a7a321260c6f33f946
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877816B2

Reaction notes

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