T. Prisinzano et al. / Tetrahedron: Asymmetry 15 (2004) 1053–1058
1057
4.10. (R)-())-[2-(Diphenyl)methanesulfinyl]acetamide
(R)-())-3
remove any solid material and then stirred at room
temperature overnight. The solvent was removed under
reduced pressure and H2O added to the residue. The
aqueous mixture was made acidic (pH ¼ 2) by the
addition of concd HCl. The resulting precipitate was
collected by filtration and dried to afford 9.5 g (92%) of 9
as a white solid, mp 105 ꢂC (lit.23 118–120 ꢂC): 1H NMR
(DMSO-d6): d 10.6 (bs, 1H); 8.9 (bs, 1H); 7.1–7.5 (m,
10H); 5.4 (s, 1H); 3.4 (s, 2H); 13C NMR (DMSO-d6):
d 166.3, 141.8, 129.3, 128.7, 128.0, 127.9, 53.7, 32.7.
A mixture of (R)-())-10 (2.0 g, 7.3 mmol), iodomethane
(1.1 g, 8.0 mmol), and K2CO3 (1.1 g, 8.0 mmol) in ace-
tone (125 mL) was heated at reflux overnight. The sol-
vent was removed under reduced pressure and H2O
added to the residue. The aqueous mixture was
extracted with CH2Cl2 (350 mL). The combined CH2Cl2
portion was washed with saturated NaCl (100 mL) and
dried over Na2SO4. Removal of the solvent under
reduced pressure afforded a crude solid that was
recrystallized from isopropyl ether to afford 1.4 g (68%)
of the corresponding methyl ester as a white solid, mp
106–108 ꢂC (lit.29 109–110 ꢂC). A mixture of the ester
(2.0 g, 6.9 mmol), NH4Cl (0.5 g, 8.5 mmol), concd
NH4OH (35 mL), and MeOH (10 mL) was stirred at
room temperature overnight. The resulting precipitate
was collected by filtration and recrystallized from
4.13. [2-(Diphenyl)methanesulfinyl]-N-hydroxy-acetamide
( )-8
A solution of 9 (5.0 g, 18.3 mmol) and 30% H2O2
(2.0 mL, 40 mmol) in acetic acid (50 mL) was stirred at
40 ꢂC overnight. The mixture was poured into H2O (mL)
and a white precipitate formed. The solid was collected
and recrystallized from a mixture of ethyl acetate/iso-
propyl alcohol, 3:2 to afford 3.8 g (72%) of ( )-8 as a
white solid, mp 156–157 ꢂC (lit.23 159–160 ꢂC): 1H NMR
(DMSO-d6): d 10.8 (bs, 1H); 9.1 (bs, 1H); 7.3–7.5 (m,
10H); 5.4 (s, 1H); 3.3 (d, J ¼ 13:2 Hz, 1H); 3.0 (d,
J ¼ 13:2 Hz, 1H); 13C NMR (DMSO-d6): d 161.1, 137.0,
134.9, 129.7, 129.1, 128.5, 128.0, 69.0, 53.8.
diisopropyl ether to afford 1.1 g (55%) of (R)-())-3 as a
22
white solid, mp 156–157 ꢂC (lit.29 153–154 ꢂC): ½aꢁ
D
)76.6 (c ¼ 1:0, CHCl3): 1H NMR (DMSO-d6): d 7.3–7.6
(m, 10H); 7.1 (s, 1H); 5.6 (s, 1H); 5.2 (s, 1H); 3.5 (d,
J ¼ 14:4 Hz, 1H); 3.1 (d, J ¼ 14:4 Hz, 1H); 13C NMR
(DMSO-d6): d 166.4, 137.2, 134.9, 129.7, 129.0, 128.5,
128.0, 68.8, 56.2.
4.11. (S)-(+)-[2-(Diphenyl)methanesulfinyl]acetamide (S)-
(+)-3
Acknowledgements
The authors thank the College of Pharmacy and the
Biological Sciences Funding Program of The University
of Iowa for financial support of this work.
A mixture of (S)-(+)-10 (1.0 g, 3.6 mmol), iodomethane
(0.6 g, 4.0 mmol), and K2CO3 (0.7 g, 4.0 mmol) in ace-
tone (80 mL) was heated at reflux overnight. The solvent
was removed under reduced pressure and H2O added to
the residue. The aqueous mixture was extracted with
CH2Cl2 (350 mL). The combined CH2Cl2 portion was
washed with saturated NaCl (100 mL) and dried over
Na2SO4. Removal of the solvent under reduced pressure
afforded a crude solid that was recrystallized from iso-
propyl ether to afford 0.7 g (65%) of the corresponding
methyl ester as a white solid, mp 106–108 ꢂC (lit.29 109–
110 ꢂC). A mixture of the ester (0.7 g, 2.3 mmol), NH4Cl
(0.2 g, 2.8 mmol), concd NH4OH (15 mL), and MeOH
(2 mL) was stirred at room temperature overnight. The
resulting precipitate was collected by filtration and
recrystallized from diisopropyl ether to afford 0.4 g
(54%) of (S)-(+)-3 as a white solid, mp 153–154 ꢂC (lit.29
References and notes
1. Becker, P. M.; Schwartz, J. R.; Feldman, N. T.; Hughes,
R. J. Psychopharmacology 2004, 171, 133–139.
2. Nishino, S.; Mignot, E. Prog. Neurobiol. 1997, 52, 27–
78.
3. Scammell, T. E. Ann. Neurol. 2003, 53, 154–166.
4. Pliszka, S. R. CNS Spectrosc. 2003, 8, 253–258.
5. Spencer, T.; Biederman, J. J. Atten. Disord. 2002, 6 (Suppl.
1), S109–S119.
6. Teitelman, E. Am. J. Psychiatry 2001, 158, 970–971.
7. Webster, L.; Andrews, M.; Stoddard, G. Pain Med. 2003,
4, 135–140.
8. Gold, L. H.; Balster, R. L. Psychopharmacology 1996, 126,
286–292.
22
1
153–154 ꢂC): ½aꢁ +76.7 (c ¼ 0:99, CHCl3): H NMR
D
(DMSO-d6): d 7.3–7.6 (m, 10H); 7.1 (s, 1H); 5.6 (s, 1H);
5.2 (s, 1H); 3.5 (d, J ¼ 14:4 Hz, 1H); 3.1 (d, J ¼ 14:4 Hz,
1H); 13C NMR (DMSO-d6): d 166.4, 137.2, 134.9, 129.7,
129.0, 128.5, 128.0, 68.8, 56.2.
9. Teitelman, E. Am. J. Psychiatry 2001, 158, 1341.
10. Ferraro, L.; Antonelli, T.; OꢀConnor, W. T.; Tanganelli,
S.; Rambert, F. A.; Fuxe, K. Biol. Psychiatry 1997, 42,
1181–1183.
11. Ferraro, L.; Antonelli, T.; Tanganelli, S.; OꢀConnor,
W. T.; Perez de la Mora, M.; Mendez-Franco, J.;
Rambert, F. A.; Fuxe, K. Neuropsychopharmacology
1999, 20, 346–356.
12. Malcolm, R.; Book, S. W.; Moak, D.; DeVane, L.;
Czepowicz, V. Am. J. Addict 2002, 11, 247–249.
13. Dackis, C. A.; Lynch, K. G.; Yu, E.; Samaha, F. F.;
Kampman, K. M.; Cornish, J. W.; Rowan, A.; Poole, S.;
White, L.; OꢀBrien, C. P. Drug Alcohol Depend. 2003, 70,
29–37.
4.12. 2-Benzhydrylsulfanyl-N-hydroxyacetamide 9
A solution of hydroxylamine hydrochloride (5.3 g,
75.6 mmol) in MeOH (40 mL) was added to a solution of
potassium hydroxide (7.5 g, 133.7 mmol) in MeOH
(40 mL). The resulting solution was then treated with a
solution of 7 (10.8 g, 37.7 mmol) in MeOH (40 mL). The
resulting mixture was stirred for 15 min and filtered to