Hydrochloric Acid → (4-bromophenyl)-(S)-1-pyrrolidin-2-ylmethylamine

温度

100 °C

2.45 g (10.00 mmol) of potassium phosphate monohydrate was added under argon to a mixture of 1.42 g (5.00 mmol) of 1-bromo-4-iodobenzene, 1.00 g (5.00 mmol) of tert-butyl (S)-2-aminomethylpyrrolidine-1-carboxylate, 48 mg (0.25 mmol) of CuI, and 97 mg (0.50 mmol) of N,N-diethylsalicylamide in 5 mL of DMF and the mixture was stirred for 160 hours at 100° C. The reaction mixture was cooled to RT, combined with 100 mL of 4M aqueous HCl, and stirred for 1 hour at RT. The aqueous phase was washed with MTBE, made basic with concentrated aqueous ammonia, and exhaustively extracted with MTBE. The combined organic extracts were dried over magnesium sulfate, filtered through activated charcoal, and evaporated down in vacuo. The crude product was purified by MPLC (Hyperprep HS C18, 8 μm, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v). The eluates were evaporated down in vacuo and the residue was neutralized with sat. aqueous sodium bicarbonate solution. The aqueous phase was extracted with DCM, dried over magnesium sulfate and evaporated down in vacuo. Yield: 0.20 g (16% of theoretical); C11H15BrN2 (M=255.2); calc.: molpeak (M+H)+: 255/257 (Br); found: molpeak (M+H)+:255/257 (Br); HPLC-MS: 3.90 minutes (method B).

1. temperatureThe reaction mixture was cooled to RT
2. stirringstirred for 1 hour at RT
3. washThe aqueous phase was washed with MTBE
4. extractionexhaustively extracted with MTBE
5. dry with materialThe combined organic extracts were dried over magnesium sulfate
6. filtrationfiltered through activated charcoal
7. customevaporated down in vacuo
8. customThe crude product was purified by MPLC (Hyperprep HS C18, 8 μm, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v)
9. customThe eluates were evaporated down in vacuo
10. extractionThe aqueous phase was extracted with DCM
11. dry with materialdried over magnesium sulfate
12. customevaporated down in vacuo
13. custom3.90 minutes (method B)

ORDレコード

ord-c4a2cf3e57f14155852b03723d0a3f39

出典データセット

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07592358B2