Sodium Iodide → Ethyl 3-(4-methoxyphenyl)-2,2-dimethylpropanoate

Ethyl iso-butyrate (35.0 g, 0.30 mol) was added to a solution of lithium N,N-diisopropyl amide (prepared from N,N-diisopropylamine (38.1 g, 0.38 mol) and n-BuLi (207 mL, 0.33 mol, 1.6 M solution in hexanes)) in dry tetrahydrofuran (1 L) at −78° C. over a 30 min period under N2 atmosphere. After the addition was complete, the reaction was stirred for 1 h after which HMPA (100 mL), NaI (67.0 g, 0.44 mol) and 4-methoxybenzyl chloride (39.3 g, 0.25 mol) were added sequentially. The reaction was then warmed to room temperature and stirred for additional 16 h before quenching at 0° C. with saturated NH4Cl solution (250 mL) and the mixture was extracted with EtOAc (2×1 L). The combined organic layers were washed successively with 2 N HCl (2×300 mL), saturated sodium bicarbonate solution (2×300 mL), and brine (400 mL), dried over Na2SO4 and filtered. Concentration of the filterate and purification of the resulting residue by flash column chromatography (silica gel, 100:0 to 96:4 hexane/EtOAc) afforded 54.0 g (90%) of ethyl 2,2-dimethyl-3-(4-methoxyphenyl)propanoate as a light yellow oil; 1H NMR (200 MHz, CDCl3) δ 7.03 (d, J=8.7 Hz, 2H), 6.79 (d, J=8.7 Hz, 2H), 4.10 (q, J=7.3 Hz, 2H), 3.78 (s, 3H), 2.78 (s, 2H), 1.23 (t, J=7.3 Hz, 3H), 1.15 (s, 6H).

1. additionAfter the addition
2. additionwere added sequentially
3. custombefore quenching at 0° C. with saturated NH4Cl solution (250 mL)
4. extractionthe mixture was extracted with EtOAc (2×1 L)
5. washThe combined organic layers were washed successively with 2 N HCl (2×300 mL), saturated sodium bicarbonate solution (2×300 mL), and brine (400 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customConcentration of the filterate and purification of the resulting residue by flash column chromatography (silica gel, 100:0 to 96:4 hexane/EtOAc)

ORD record

ord-42f339b949e74a1db296e4f76c68fd4a

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902394B2