3250
C. Schjøth-Eskesen and H. H. Jensen
3-(benzyloxy)benzene-1-sulfonyl chloride (7) (1.01 g, 3.6 mmol) in diethy-
lether (12 mL). The biphasic mixture was vigorously stirred at 0ꢂC and
during the night allowed to warm to room temperature. The mixture
was diluted with CH2Cl2 and made acidic by adding an aqueous
solution of 3% hydrochloric acid. The water phase was removed,
and the organic phase was washed three times with a sodium carbo-
nate solution. It was dried over MgSO4, and the solvent was
removed. The residue was dissolved in CH2Cl2 and was again washed
with sodium carbonate three times and dried. Removal of the solvent
gave the title compound (806 mg, 96%) as a light pink oil without
the need for further purification. Rf 0.67 (petrol=EtOAc=Et3N
65.3:32.7:2). [a]D 68.8 (c 1.0, CHCl3). 1H NMR (CDCl3, 400 MHz)
d 7.45–7.31 (m, 8H), 7.21–7.15 (m, 1H), 5.13 (s, 2H), 3.66–3.57 (m,
1H), 3.38–3.31 (m, 1H), 3.15–3.06 (m, 1H), 3.01–2.86 (m, 2H),
2.49–2.30 (m, 2H), 2.11–1.85 (m, 3H), 1.81–1.18 (m, 10H), 0.91
(d, 3H, J 6.0 Hz). 13C NMR (CDCl3, 100 MHz) d 159.0, 138.9,
136.4, 130.3, 128.9, 128.4, 127.7, 120.2, 120.0, 113.5, 70.5, 59.2,
55.8, 54.2, 49.1, 34.4, 33.7, 31.1, 24.2, 22.1. HRMS(ES): calcd. for
1
C25H34N2O3SH 443.2368; found 443.2363. The H NMR data were
similar with those previously reported.[2]
(R)-3-(2-(2-(4-Methylpiperidin-1-yl)ethyl)pyrrolidin-1-ylsulfonyl)phenol
Hydrochloric Salt (SB 269970) (9)
A solution of sulfonamide 8 (1.00 g, 2.3 mmol) in ethanol (30 mL) and
concentrated hydrochloric acid (1.0 mL) was hydrogenated over
palladium on charcoal (10%, 180 mg) at room temperature for 72 h.
During the course of the reaction, more palladium catalyst was added
twice. The reaction mixture was filtered through celite with methanol
and concentrated. The residue was dissolved in hot methanol and filtered.
Removal of the solvent gave a solid, which was purified by flash chroma-
tography (CHCl3=CH3OH 9:1) to give SB 269970 (0.69 g, 79%) as a fine
white powder. Rf 0.38 (CHCl3=CH3OH 9:1). [a]D 35.2 (c 1.0, DMSO). 1H
NMR (DMSO-d6, 400 MHz) d 10.3 (s, 1H), 10.1 (b s, 1H), 7.47 (t, 1H, J
7.6 Hz), 7.32–7.24 (m, 2H), 7.14 (dd, 1H, J 1.6 Hz, J 8.4 Hz), 3.77–3.67
(m, 1H), 3.54–3.40 (m, 2H), 3.35–3.29 (m, 1H), 3.26–2.81 (m, 6H),
2.14–1.88 (m, 4H), 1.70–1.41 (m, 6H), 0.96 (d, 3H, J 6.0 Hz). 13C
NMR (DMSO-d6, 100 MHz) d 158.4, 137.7, 130.8, 120.6, 118.0, 114.2,
58.2, 53.5, 52.1, 48.8, 30.9, 30.5, 29.7, 28.4, 23.7, 21.4. 1H NMR data were
similar to those previously reported.[2] HRMS(ES) calcd. for
C18H28N2O3SH 353.1899; found 353.1893.