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5 The reaction was completed in a closed
tube with a bursting disc fitted in the top of the tube. The reaction
was completed behind a blast screen and these important safety measures should
be implemented when completing this reaction particularly when scaling
up the procedure.
6
Typical Procedure
for Heck Reaction
1-Bromo-2-methoxybenzene (0.958
mL, 7.75 mmol), methyl 3-hydroxy-2-methylenebutyrate (0.942 ml,
7.75 mmol) and N-methyldicyclohexylamine
(4.98 mL, 23.26 mmol) were added to a suspension of Pd(dbpf)Cl2 (0.126
g, 0.19 mmol) and TBAC (0.431 g, 1.55 mmol) in DMF (10 ml) under
nitrogen. The resulting suspension was stirred
at 100 ˚C
in a closed tube for 18 h (see ref. 5 for safety measures). The
solution was diluted with EtOAc (50 mL) and extracted with H2O
(50 mL) and brine (2 × 50 mL). The organic
phase was dried over MgSO4, filtered, and evaporated.
The residue was diluted with MeCN (30 mL) and loaded on to a 70
g SCX cartridge. The product was washed through with MeCN (100 mL)
and the filtrate evaporated to give methyl 2-(2-methoxybenzyl)-3-oxo-butanoate
(1.558 g, 85%) as an orange oil. ¹H
NMR (400 MHz, CDCl3): δ = 7.20 (ddd, J = 8.9, 7.6,
2.1 Hz, 1 H, CH), 7.11 (dd, J = 6.8,
3.0 Hz, 1 H, CH) 6.87-6.82 (m, 2 H, CH), 3.92 (dd, J = 8.4, 7.2
Hz, 1 H, CH), 3.83 (s, 3 H, CH3), 3.67 (s, 3 H, CH3),
3.19 (dd, J = 13.9,
7.2 Hz, 1 H, CH2), 3.10 (dd, J = 13.9,
8.2 Hz, 1 H, CH2), 2.18 (s, 3 H, CH3). ¹³C
NMR (125 MHz, CDCl3): δ = 203.1, 169.9,
157.3, 130.8, 128.1, 126.2, 120.5, 110.2, 59.0, 55.2, 52.2, 29.5,
29.4. HRMS (TOF-LCMS): m/z calcd
for C13H17O4 [M + H]+:
237.1121; found: 237.1122.