Nitrogen → trans-2,3,4-Trimethoxycinnamic acid chloride
Reaction equation
N#N.[CH3:3][O:4][C:5]1[C:15]([O:16][CH3:17])=[C:14]([O:18][CH3:19])[CH:13]=[CH:12][C:6]=1/[CH:7]=[CH:8]/[C:9](O)=[O:10].C(Cl)(=O)C([Cl:23])=O>C(Cl)Cl.CN(C=O)C>[CH3:3][O:4][C:5]1[C:15]([O:16][CH3:17])=[C:14]([O:18][CH3:19])[CH:13]=[CH:12][C:6]=1/[CH:7]=[CH:8]/[C:9]([Cl:23])=[O:10]Participants
Procedure
(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve trans-2,3,4-Trimethoxycinnamic acid (50) (200 mg, 0.84 mmol) in anhydrous DCM (4.4 mL) at it and add anhydrous DMF (3 drops, cat. amount). Then add slowly oxalyl chloride (96 μL, 1.09 mmol) stir the turbid mixture for additional 2 h at rt. Remove solvent and dry the residue in oil pump vacuum to obtain trans-2,3,4-Trimethoxycinnamic acid chloride (51) (ca. 0.84 mmol) as an yellow solid. Dissolve acid chloride (51) (108 mg, 0.42 mmol) in anhydrous DCM (4.0 mL) and add it to an ice cooled solution of Methyl 3-amino-4-methylbenzoate (52) (69 mg, 0.42 mmol) in anhydrous DCM (2.0 mL) and anhydrous pyridine (1.2 mL). Stir the resulting reaction mixture at rt overnight. Pour the reaction mixture into ice cooled 1M aqu. HCl, extract with EtOAc (3×), wash the combined organic layer with brine and dry it with Na2SO4. Purify the crude product by filtration through a short pad of silica gel with EtOAc and remove solvent to obtain 4-Methyl-3-[3-(2,3,4-trimethoxy-phenyl)-acryloylamino]-benzoic acid methyl ester (53) (99 mg, 61%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): 2.35 (s, 3H); 3.87 (s, 3H); 3.88 (s, 6H); 3.91 (br.s, 3H); 6.59 (d, 1H, J=15.6 Hz); 6.68 (d, 1H, J=8.6 Hz); 7.08 (br.s, 1H); 7.20-7.29 (m, 2H); 7.77 (br.d, 1H, J=8.6 Hz); 7.90 (d, 1H, J=15.6 Hz); 8.55 (br.s 1H).
Workup
- custom(The following reaction
- customRemove solvent and dry the residue in oil pump vacuum
Sources & evidence
- ORD record
- ord-3732d41c3a7043318b7e1e0a53b1407d
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08367677B2
Reaction notes
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