Dimethylformamide dimethyl acetal → Methyl 2-(4-cyano-3-fluoro-2-methylphenyl)-3-(dimethylamino)acrylate

HRID 526459Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:5]([CH3:14])[C:4]=1[F:15])#[N:2].CO[CH:18](OC)[N:19]([CH3:21])[CH3:20].[Cl-].[Li+]>O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=[CH:18][N:19]([CH3:21])[CH3:20])[C:10]([O:12][CH3:13])=[O:11])=[C:5]([CH3:14])[C:4]=1[F:15])#[N:2]

Participants

Conditions

Temperature: 10 °C

Procedure

Combined methyl 2-(4-cyano-3-fluoro-2-methylphenyl)acetate (10.0 g, 48.3 mmol), 1,1-dimethoxy-N,N-dimethylmethanamine (17.25 g, 145 mmol), and solid lithium chloride (0.205 g, 4.83 mmol) and heated to 105° C. for 1.5 h. The mixture was cooled to 10° C. and water (210 mL) was added slowly. The solid was collected by vacuum filtration, dissolved in DCM and was purified by column chromatography to afford the title compound (7.95 g, 63%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.07 (d, J=2.53 Hz, 3H) 2.54-2.86 (m, 6H) 3.50 (s, 3H) 7.10 (d, J=7.83 Hz, 1H) 7.62 (s, 1H) 7.63-7.66 (m, 1H). ESI-MS m/z [M+H]+ 263.2.

Workup

filtrationThe solid was collected by vacuum filtration
dissolutiondissolved in DCM
customwas purified by column chromatography

Sources & evidence

ORD record: ord-5c592f8210f54834a936553cbc3d798b
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345713B2

Reaction notes

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