Methanesulfonyl chloride → HCID 21477178, compound

Temperature

0 °C

To a flame-dried flask containing a solution of 1-(3-bromophenyl)propanol of Preparation 38 (3.50 g) and triethylamine (4.54 mL) in dry methylene chloride (18 mL) at 0° C. under nitrogen is added methanesulfonyl chloride (1.39 mL) over 1 min. The resulting mixture is stirred at 0° C. for 2 hrs, diluted with water (8 mL), and the layers are separated. The aqueous phase is extracted with methylene chloride (25 mL) and the combined organic phase is washed with saline (5 mL), dried over sodium sulfate, and concentrated under reduced pressure to give an oily intermediate. A mixture containing the intermediate and lithium bromide (1.42g) in acetone (50 mL) under nitrogen is refluxed for 4 hrs, cooled to RT, concentrated to remove acetone, re-diluted with methylene chloride (40 mL) and water (20 mL), and the layers are separated. The aqueous phase is extracted with methylene chloride (40 mL) and the combined organic phase is washed with saline (15 mL), dried over sodium sulfate, and concentrated to give a crude oil which is then chromatographed on silica gel (70-230 mesh, 250 g), eluting with ethyl acetate/hexane (5/95). Pooling of fractions with an Rf =0.63 by TLC (ethyl acetate/hexane, 25/75) and removal of solvent under reduced pressure gives the title compound.

1. additionTo a flame-dried flask containing
2. customthe layers are separated
3. extractionThe aqueous phase is extracted with methylene chloride (25 mL)
4. washthe combined organic phase is washed with saline (5 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give an oily intermediate
8. temperatureis refluxed for 4 hrs
9. temperaturecooled to RT
10. concentrationconcentrated
11. customto remove acetone
12. additionre-diluted with methylene chloride (40 mL) and water (20 mL)
13. customthe layers are separated
14. extractionThe aqueous phase is extracted with methylene chloride (40 mL)
15. washthe combined organic phase is washed with saline (15 mL)
16. dry with materialdried over sodium sulfate
17. concentrationconcentrated
18. customto give a crude oil which
19. customis then chromatographed on silica gel (70-230 mesh, 250 g)
20. washeluting with ethyl acetate/hexane (5/95)
21. customPooling of fractions with an Rf =0.63 by TLC (ethyl acetate/hexane, 25/75) and removal of solvent under reduced pressure

ORD record

ord-ae9350a2bb6345e7991a7e566d4b407c

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05686486