Hydrochloric Acid → Ethyl 2-(2-chloro-4-cyanophenyl)-3-(dimethylamino)acrylate

HRID 526434Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][C:3]=1[CH2:10][C:11]([O:13][C:14]([CH3:17])(C)C)=[O:12].Cl.O1CCOCC1.ClC1C=C(C#N)C=CC=1CC(OCC)=O.C(O[CH:43](OCC)[N:44]([CH3:46])[CH3:45])C>C(O)C.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][C:3]=1[C:10](=[CH:43][N:44]([CH3:46])[CH3:45])[C:11]([O:13][CH2:14][CH3:17])=[O:12]

Participants

Conditions

Temperature: 60 °C

Procedure

Combined tert-butyl 2-(2-chloro-4-cyanophenyl)acetate (274 mg, 1.089 mmol) and 4N HCl in dioxane (0.136 mL, 0.544 mmol) in ethanol (2.51 mL). The mixture was stirred for 16 hours at 60° C., then concentrated by rotary evaporation and combined with ethyl 2-(2-chloro-4-cyanophenyl)acetate (0.243 g, 1.086 mmol) and 1,1-diethoxy-N,N-dimethylmethanamine (0.931 mL, 5.43 mmol) in DMF (2.173 mL) and stirred for 16 hours at 100° C. The reaction was concentrated in rotary evaporation and purified on a NH silica gel column eluting with hexanes and EtOAc to give the title compound (164 mg, 54%) as a yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 1.04-1.29 (m, 1H) 3.96-4.31 (m, 1H) 7.38 (d, J=7.8 Hz, 1H) 7.49 (dd, J=7.8, 1.8 Hz, 1H) 7.63-7.71 (m, 1H).

Workup

concentrationconcentrated by rotary evaporation
stirringstirred for 16 hours at 100° C
concentrationThe reaction was concentrated in rotary evaporation
custompurified on a NH silica gel column
washeluting with hexanes and EtOAc

Sources & evidence

ORD record: ord-46d66fee614c4e1d88c5068f66daffc2
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345713B2

Reaction notes

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