Reaction #46533

Reaction equation

5-bromo-2-(methoxycarbonylmethyl)aminopyridine

tert-butyl acrylate

DIEA

P(o-tol)3

→

title compound

Yield 93.3%

tert-Butyl (E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]acrylate

Yield 93.3%

Solvents

propionitrile

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureat reflux
3. 3
   Concentrationthen was concentrated to dryness
4. 4
   OtherThe residue was purified by flash chromatography on silica gel (40% EtOAc/hexane)

Procedure

A solution of 5-bromo-2-(methoxycarbonylmethyl)aminopyridine (4.69 g, 19.1 mmole, from Preparation 28 (c)), tert-butyl acrylate (11.2 mL, 76.5 mmole), DIEA (6.7 mL, 38.5 mmole), Pd(OAc)2 (215 mg, 1 mmole), and P(o-tol)3 (583 mg, 2 mmole) in propionitrile (100 mL) was purged with Ar, then was heated at reflux. After 18 h, the reaction was allowed to cool to room temperature then was concentrated to dryness. The residue was purified by flash chromatography on silica gel (40% EtOAc/hexane) to give the title compound (5.21 g, 93%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1 H), 7.62 (dd, 1 H), 7.47 (d, J=16.0 Hz, 1 H), 6.48 (d, J=8.7 Hz, 1 H), 6.17 (d, J=15.9 Hz, 1 H), 5.21 (br s, 1 H), 4.20 (d, J=5.4 Hz, 2 H), 3.79 (s, 3 H), 1.52 (s, 1 H).

Source