Diisopropylamine → 1-(4-Bromobutyl)cyclopentanecarboxylic acid methyl ester

Temperature

0 °C

To a solution of diisopropylamine (150 mmol, 21 mL) in THF (100 mL) at −10° C. was added dropwise a 2.5M solution of n-butyl lithium in hexanes (145 mmol, 58 mL) while maintaining the temperature below 0° C. After the addition was complete, the solution was stirred for 30 min at 0° C., then it was cooled to −70° C. using a dry ice/acetone bath. A solution of methyl cyclopentanecarboxylate (100 mmol, 13.1 g) in THF (20 mL) was added dropwise at −70° C. maintaining the reaction temperature between −60 to −70° C. The mixture was then stirred for 1 h at −50 to −60° C. and a solution of 1,4-dibromobutane (100 mmol, 21.59 g) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 1 h at −60 to −70° C. The cooling bath was removed and the reaction was allowed to equilibrate to room temperature and stirred overnight. The reaction mixture then was poured into a saturated solution of ammonium. chloride (200 mL) and the mixture was extracted with diethyl ether (2×100 mL). The combined extracts were washed with brine (150 mL), dried (MgSO4), filtered and the solution was concentrated under reduced pressure. The resulting residue was distilled at 120-133° C./2.5 mm Hg to obtain 12.8 g (48%) of 1-(4-bromobutyl)cyclopentanecarboxylic acid methyl ester as a colorless oil. HR MS: Obs. mass, 262.0565. Calcd. mass, 262.0568, (M+).

1. temperaturewhile maintaining the temperature below 0° C
2. additionAfter the addition
3. temperatureit was cooled to −70° C.
4. temperaturemaintaining the reaction temperature between −60 to −70° C
5. stirringThe mixture was then stirred for 1 h at −50 to −60° C.
6. stirringthe light brown suspension was stirred for 1 h at −60 to −70° C
7. customThe cooling bath was removed
8. customto equilibrate to room temperature
9. stirringstirred overnight
10. additionThe reaction mixture then was poured into a saturated solution of ammonium
11. extractionchloride (200 mL) and the mixture was extracted with diethyl ether (2×100 mL)
12. washThe combined extracts were washed with brine (150 mL)
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationthe solution was concentrated under reduced pressure
16. distillationThe resulting residue was distilled at 120-133° C./2.5 mm Hg

ORD record

ord-9ca94c78c6ac405c9c8ca62f7d050d86

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06458844B2