Diisopropylamine → Methyl 5-(2,5-Dichlorophenyl)pentanoate

Temperature

0 °C

Diisopropylamine (841 μl, 6 mmol) was added to 20 mL of THF under nitrogen atmosphere and cooled to 0° C. 5.5 ml of 2.5 N n-butyllithium (55.5 mmol) was added and the reaction was stirred for 20 minutes. The reaction was then cooled to −78° C. 2,5-Dichlorotoluene (642 μL, 5 mmol) was added and stirring was continued for 2 hours at −78° C. Trimethyl 4-bromoorthobutyrate (1.14 g, 5 mmol) was added to the reaction mixture in 10 mL THF. The reaction was stirred for 5 minutes at −78° C., allowed to come to room temperature and stirred overnight. The reaction was worked-up by adding 10 mL of saturated KH2PO4, removal of most of the THF on a rotary evaporator followed by partitioning of the aqueous residue between ethyl acetate and 1 N HCl. The organic phase was washed twice with 1 N HCl, once with 5% NaHCO3, dried over sodium sulfate and concentrated to a residue. Flash chromatography (silica gel; hexane/toluene (39/1)) of the residue gave 1.10 g (84%; GC retention time=15.80 minutes) of a water white oil

1. temperatureThe reaction was then cooled to −78° C
2. stirringstirring
3. waitwas continued for 2 hours at −78° C
4. stirringThe reaction was stirred for 5 minutes at −78° C.
5. customto come to room temperature
6. stirringstirred overnight
7. additionby adding
8. custom10 mL of saturated KH2PO4, removal of most of the THF
9. customon a rotary evaporator
10. customby partitioning of the aqueous residue between ethyl acetate and 1 N HCl
11. washThe organic phase was washed twice with 1 N HCl, once with 5% NaHCO3
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated to a residue
14. customFlash chromatography (silica gel; hexane/toluene (39/1)) of the residue gave 1.10 g (84%; GC retention time=15.80 minutes) of a water white oil

ORD record

ord-c765677ec151406db2a98a4265ea827c

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06204005B1