1,4-Dibromobutane → 1-Pyrrolidineethanol,beta-methyl-,(betaS)-(9CI)

Potassium carbonate (41.4 g, 0.30 moles) was added to a solution of (S)-(+)-2-amino-1-propanol (11.27 g, 0.15 moles, Aldrich) in anhydrous acetonitrile (1.5 L) then 1,4-dibromobutane (17.9 mL, 0.15 moles, Aldrich) was added. The resulting mixture was refluxed for 24 hours then cooled to room temperature and filtered. The filtrate was concentrated under vacuum to a straw-colored solid which was dissolved in dichloromethane (150 mL) and again concentrated under vacuum to afford a straw-colored solid. This crude material, believed to be a mixture of the hydrobromide salt and the free base of the product, was again dissolved in dichloromethane (200 mL). Solid potassium carbonate and the mixture was stirred vigorously for 3 hours then filtered and concentrated under vacuum to afford a straw-colored solid. This solid, believed to still be partially the hydrobromide salt, was partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL). The layers (upper layer organic, lower layer aqueous) were separated and the aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to an amber oil. This crude product was purified by short-path vacuum distillation to afford the title compound as a colorless liquid (bp 53–54.5° C. at 1.5 mm Hg). NMR: (CDCl3, 600 MHz) δ 3.59 & 3.36 (2H, 2 dd, J=4, 10 Hz, H1), 2.64–2.72 (1H, m, H2), 2.54–2.62 (4H, m, H2′ & H5′), 1.72–1.80 (4H, m, H3′ & H4′),1.04 (3H, d, J=7 Hz, H3); MS (electrospray): m/e 130 (M+H), 112 (M−OH). [α]D+0.9°

1. temperatureThe resulting mixture was refluxed for 24 hours
2. filtrationfiltered
3. concentrationThe filtrate was concentrated under vacuum to a straw-colored solid which
4. dissolutionwas dissolved in dichloromethane (150 mL)
5. concentrationagain concentrated under vacuum
6. customto afford a straw-colored solid
7. filtrationthen filtered
8. concentrationconcentrated under vacuum
9. customto afford a straw-colored solid
10. customwas partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL)
11. customThe layers (upper layer organic, lower layer aqueous) were separated
12. extractionthe aqueous layer was extracted with dichloromethane (2×100 mL)
13. dry with materialThe combined organic layers were dried over magnesium sulfate
14. filtrationfiltered
15. customevaporated to an amber oil
16. distillationThis crude product was purified by short-path vacuum distillation

ORD record

ord-0b0351c712da48598b70df6cbd468ba6

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07138426B2