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

HRID 578961Notes

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, 3 H) 2.54-2.86 (m, 6 H) 3.50 (s, 3 H) 7.10 (d, J=7.83 Hz, 1 H) 7.62 (s, 1 H) 7.63-7.66 (m, 1 H). 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-0b6b1f50bec34d878f55bf09d6ddddc2
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040522B2

Reaction notes

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