Diisopropylamine → 1-(2-Methoxyethyl)Cyclopentane Carboxylate Methyl Ester

Temperature

0 °C

To a solution of diisopropylamine (21 mL, 150 mmol) in THF (100 mL) was added dropwise a solution of n-butyl lithium (58 mL, 145 mmol) in hexanes at −10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of methyl cyclopentane carboxylate (12.8 g, 100 mmol) in THF (20 mL) was added dropwise at −70° C. maintaining the internal temperature between −60 to −70° C. After addition, the reaction mixture was stirred for 30 min at −50 to −60° C. Then, a solution of 2-methoxy ethyl bromide (12.5 g, 90 mmol) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 30 min at −60 to −70° C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (250 mL) and was extracted with ether (2×100 mL). The combined extracts were washed with a saturated solution of sodium chloride (100 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum to afford 16.55 g of crude product as a black liquid. Distillation at 70-75° C./1.5 mm Hg afforded 7.98 g of a colorless oil and a further 2.76 g as a light yellow oil for a total yield of 10.74 g (64%). HR MS (C10H18O3): Obs. mass, 186.1257. Calcd. mass, 186.1256 (M+).

1. temperaturewhile maintaining the temperature below 0° C
2. additionAfter addition
3. temperaturemaintaining the internal temperature between −60 to −70° C
4. additionAfter addition
5. stirringthe reaction mixture was stirred for 30 min at −50 to −60° C
6. stirringthe light brown suspension was stirred for 30 min at −60 to −70° C
7. temperatureto warm to room temperature
8. stirringstirred overnight
9. extractionwas extracted with ether (2×100 mL)
10. washThe combined extracts were washed with a saturated solution of sodium chloride (100 mL)
11. dry with materialdried over anhydrous magnesium sulfate
12. filtrationAfter filtration of the drying agent
13. concentrationthe solution was concentrated under vacuum
14. customto afford 16.55 g of crude product as a black liquid
15. distillationDistillation at 70-75° C./1.5 mm Hg

ORD record

ord-8ec901b33bee48388f88f2744b01a10d

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06806365B2