Diisopropylamine → Methyl 2,2-dimethyl-3-(4-nitrophenyl)propanoate

Temperature

-50 °C

n-BuLi (1.15M in hexane) (10.1 mL, 11.6 mmol) was added dropwise to a solution of diisopropylamine (1.64 mL, 11.6 mmol) in THF (20 mL) in a dry ice/acetone bath. The mixture was stirred and warmed to ˜−50° C. before being cooled again and methyl 2-methylpropanoate (1.3 mL, 11 mmol) was added over 5 min. The mixture was stirred for 30 min before a solution of the nitrobenzyl bromide (2 g in 15 mL THF) was added dropwise over 20 min. The temperature was kept below −65° C. during the addition then left in the cool bath to warm slowly to RT and stirred for 16 hr. The mixture was quenched with NH4Cl (sat.) and left at RT for 9 days. The quenched reaction mixture was diluted with water and EtOAc and extracted into EtOAc (3×40 mL). The organics were combined, dried with brine, then solid MgSO4, filtered and the solvent removed to afford a crude oil. The oil was dissolved in ˜2 mL DCM and applied to a silica column to afford (i) 1.4 g (64%). 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J=8.8 Hz, 2H), 7.27 (d, J=9.6 Hz, 2H), 3.67 (s, 3H), 2.96 (s, 2H), 1.21 (s, 6H).

1. temperaturebefore being cooled again
2. additionwas added dropwise over 20 min
3. additionThe temperature was kept below −65° C. during the addition
4. waitthen left in the cool bath
5. temperatureto warm slowly to RT
6. stirringstirred for 16 hr
7. customThe mixture was quenched with NH4Cl (sat.)
8. customThe quenched reaction mixture
9. extractionextracted into EtOAc (3×40 mL)
10. dry with materialdried with brine
11. filtrationsolid MgSO4, filtered
12. customthe solvent removed
13. customto afford a crude oil

ORD record

ord-71f9b0ab02874955acc2029047276078

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09060515B2