2-Bromophenol → 3-(2-Bromophenoxy)pyrrolidine

1-tert-Butyloxycarbonyl-3-hydroxypyrrolidine (1 g), 2-bromophenol (710 mg) and triphenylphosphine (1.29 g) were dissolved in tetrahydrofuran (15 ml) and the mixture cooled in an ice bath before dropwise addition of diisopropyl azodicarboxylate (0.96 ml). The mixture was allowed to warm to room temperature over 3 h, concentrated in vacuo, partitioned between ether (50 ml) and water (50 ml) and the aqueous phase was extracted further with ether (50 ml). The combined organic phases were washed with water (2×25 ml), brine (2×25 ml), dried (MgSO4) and concentrated in vacuo. The product was dissolved in dichloromethane (10 ml) and trifluoroacetic acid (5 ml) was added and the reaction stirred for 1 h. The mixture was concentrated in vacuo and the residue was purified by cation exchange chromatography eluting with ammonia/methanol/dichloromethane mixtures. This gave the title compound as a pale orange oil (437 mg).

1. concentrationconcentrated in vacuo
2. custompartitioned between ether (50 ml) and water (50 ml)
3. extractionthe aqueous phase was extracted further with ether (50 ml)
4. washThe combined organic phases were washed with water (2×25 ml), brine (2×25 ml)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. dissolutionThe product was dissolved in dichloromethane (10 ml)
8. additiontrifluoroacetic acid (5 ml) was added
9. concentrationThe mixture was concentrated in vacuo
10. customthe residue was purified by cation exchange chromatography
11. washeluting with ammonia/methanol/dichloromethane mixtures

ORD record

ord-23a7051504ff4f85882258bee14f84c5

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07125896B2