Diisopropylamine → Ethyl 2-butylhexanoate

Temperature

-40 °C

Diisopropylamine (45.5 g, 450 mmol) was dissolved in anhydrous THF 150 mL and cooled to −40° C. in an acetonitrile/dry ice bath under nitrogen protection. 2.5M n-butyllithium (n-BuLi)/hexane solution (126 mL, 315 mmol) was added with stirring. After the addition, the mixture was kept in the ice water bath for 30 minutes, cooled down to −78° C. in an acetone/dry ice bath, and ethylhexanoate (43.3 g, 300 mmol) was added dropwise. The reaction mixture was stirred at the same temperature for 1 hour and then, iodobutane (60.7 g, 330 mmol) in 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) (11.5 g, 90 mmol) was added dropwise. The resulting solution was warmed to −40° C., stirred for 2 hours, and kept at room temperature overnight. The reaction mixture was quenched with a saturated NH4Cl aqueous solution, and concentrated via rotary evaporation. Into the flask, 200 mL of Et2O and 200 mL of water were added. After acidification of the mixture using a 2N HCl aqueous solution, the organic layer was separated, washed with 10% (v/v) HCl aqueous solution (150 mL×2), and concentrated via rotary evaporation. The resulting crude yellow oil was purified via vacuum distillation. The compound 16 was collected as colorless oil (45.0 g, 75%). 1H NMR (CDCl3): δ 0.86-0.90 (6H, m), 1.07-1.62 (12H, m), 1.25 (3H, t), 2.27-2.32 (1H, m), 4.12 (2H, q). MS (EI): calcd, 200.3. found M+H+, 201.2.

1. additionAfter the addition
2. temperaturecooled down to −78° C. in an acetone/dry ice bath
3. stirringThe reaction mixture was stirred at the same temperature for 1 hour
4. temperatureThe resulting solution was warmed to −40° C.
5. stirringstirred for 2 hours
6. customThe reaction mixture was quenched with a saturated NH4Cl aqueous solution
7. concentrationconcentrated via rotary evaporation
8. additionInto the flask, 200 mL of Et2O and 200 mL of water were added
9. customthe organic layer was separated
10. washwashed with 10% (v/v) HCl aqueous solution (150 mL×2)
11. concentrationconcentrated via rotary evaporation
12. distillationThe resulting crude yellow oil was purified via vacuum distillation
13. customThe compound 16 was collected as colorless oil (45.0 g, 75%)

ORD record

ord-1bcf0362302544c7b014e299ed7b9ff5

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09153785B2