Busulfan → Butyl methanesulfonate

A mixture of 1.00 g (2.18 mmol) of 5-(4′-hydroxyphenyl)-7-(dimethylamino)tetrahydrobenzo-thiepine-1,1-dioxide (obtained from Example 1402, Step 10), 2.68 g (10.88 mmol) of busulfan, and 1.50 g (10.88 mmol) of potassium carbonate in 20 mL of acetone was stirred at reflux overnight. The mixture was concentrated in vacuo and the crude was dissolved in 30 mL of ethyl acetate. The insoluble solid was filtered off and the filtrate was concentrated in vacuo. The resulting white foam was chromatographed through silica gel column, and eluted with 30% ethyl acetate/hexane to give 1.02 g (77%) of butyl mesylate intermediate as a white solid: 1H NMR (CDCl3) δ0.90 (m, 6H), 1.20-1.67 (m, 12H), 1.98 (m, 4H), 2.22 (m, 1H), 2.83 (s, 6H), 3.04 (s, 3H), 3.08 (ABq, 2H), 4.05 (t, J=5.55 Hz, 2H), 4.11 (d, J=6.90 Hz, 1H), 4.35 (t, J=6.0 Hz, 2H), 5.49 (s, 1H), 6.00 (d, J=2.4 Hz, 1H), 6.52 (dd, J=9.0 Hz, 2.7 Hz, 1H), 6.93 (d, J=9.0 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.90 (d, J=9.0 Hz, 1H)

1. temperatureat reflux overnight
2. concentrationThe mixture was concentrated in vacuo
3. dissolutionthe crude was dissolved in 30 mL of ethyl acetate
4. filtrationThe insoluble solid was filtered off
5. concentrationthe filtrate was concentrated in vacuo
6. customThe resulting white foam was chromatographed through silica gel column
7. washeluted with 30% ethyl acetate/hexane

ORD record

ord-6dd13cea9df4455597315f2dc5e64fa9

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06262277B1