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

Temperature

0 °C

Diisopropylamine (841 ul, 6 mmol) was added to 20 ml of tetrahydrofuran under nitrogen atmosphere and cooled to 0° C. 5.5 ml of 2.5 N n-butyllithium (13 mmol) was added and the reaction was stirred for 20 minutes. The reaction was then cooled to −78° C. 2,5-Dichlorotoluene (642 ul, 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 tetrahydrofuran. 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 tetrahydrofuran 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% sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated to a residue. Flash chromatogaphy (silica gel; hexane/toluene (39/1)) of the residue gave 1.10 g (84%; GC retention time=15.8 minutes) of a water white oil. 1H NMR (300 MHz, CDCl3) delta=7.24 (d, J=8.5 Hz, H3), 7.18 (d, J=2.5 Hz, H6), 7.09 (dd, J=2.5, 8.5 Hz, H4), 3.66 (s, —COOCH3), 2.69 (t, J=7.8 Hz, Ar—CH2—), 2.35 (t, J=7.0 Hz, —CH2—COO—), 1.70-1.55 (m, —CH2—CH2—CH2—CH2—).

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 tetrahydrofuran
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% sodium bicarbonate
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated to a residue
14. customFlash chromatogaphy (silica gel; hexane/toluene (39/1)) of the residue gave 1.10 g (84%; GC retention time=15.8 minutes) of a water white oil

ORD record

ord-0f7c6750b0314066b30a07f2f299e20d

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06204005B1