p-Toluenesulfonic acid → 3-(Pyrrolidin-1-yl)butan-1-ol

Pyrrolidine (28.159, 0.4 mol), toluene (200 ml), catalytic p-TsOH (200 mg) and ethyl acetoacetate (20 g, 0.15 mol) were refluxed together in a Dean-Stark apparatus under N2 for 3 hours. The reaction was cooled to room temperature and concentrated in vacuo. NaBH4 (3.1 g, 82 mmol) was dissolved in MeOH (50 ml) and cooled to 0-5° C. A portion of the previous crude reaction (5 g, 27 mmol) in MeOH (25 ml) was added to the reaction mixture and stirred for 72 hours. The reaction was quenched with an aqueous solution of NaOH (1% w/w, 50 ml) and concentrated in vacuo. The aqueous phase was extracted with TBME (3×50 ml). The combined organic extracts were dried over MgSO4, filtered, washed with TBME and concentrated in vacuo to give a mixture of the title compound, 3-pyrrolidin-1-yl-butanoic acid ethyl ester and residual TBME (3.5 g). The mixture (3.5 g) in THF (20 ml) was added to a solution of LiALH4 (1M in THF, 33.5 ml, 33.5 mmol) at 0-5° C. under N2. The reaction was allowed to warm to room temperature and stirred for 3 hours. The reaction was quenched with an aqueous solution of NaOH (1% w/w, 50 ml) at 0-5° C., filtered and washed with THF (3×20 ml). The combined organic layers were dried over MgSO4, filtered, washed with THF and concentrated in vacuo to give the title compound as a yellow oil (2 g, 73%).

1. concentrationconcentrated in vacuo
2. temperaturecooled to 0-5° C
3. additionwas added to the reaction mixture
4. customThe reaction was quenched with an aqueous solution of NaOH (1% w/w, 50 ml)
5. concentrationconcentrated in vacuo
6. extractionThe aqueous phase was extracted with TBME (3×50 ml)
7. dry with materialThe combined organic extracts were dried over MgSO4
8. filtrationfiltered
9. washwashed with TBME
10. concentrationconcentrated in vacuo
11. customto give

ORD record

ord-652a2f8d29424460b4da5603e29a79f9

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456164B2