asc.wiley-vch.de
1 h via a syringe pump. The reaction mixture was stirred at ±
78 °C for additional 2 h. The reaction was quenched with sa-
turated NH4Cl (30 mL) and the resulting mixture was ex-
tracted with ethyl acetate (3 ´ 50 mL). The combined organ-
ic layer was dried over anhydrous MgSO4. Solvent was
evaporated, and the resulting solid was recrystallized from
hexanes:ethyl acetate (90:10) to give a white crystalline 7b
(yield: 2.2 g, 84%); [a]3D0: ±128.7 (c 1.2, CH2Cl2); 1H NMR
(500 MHz, CDCl3): d = 7.46±7.20 (comp, 5 H), 4.93 (dd,
J = 11.5 Hz, 2.5 Hz, 1 H), 3.81 (t, J = 11.5 Hz, 1 H), 3.55±3.46
(comp, 2 H), 3.38 (dq, J = 14.0 Hz, 2.0 Hz, 1 H), 3.22±3.14
(comp, 2 H), 1.45 (d, J = 5.5 Hz, 1 H), 1.06 (d, J = 5.5 Hz, 1 H),
1.05 (t, J = 7.0 Hz, 3 H), 0.85 (s, 3 H), 0.83 (t, J = 7.0 Hz, 3 H);
13C NMR (125 MHz, CDCl3): d = 172.0, 137.0, 128.6, 128.4,
126.9, 70.1, 41.7, 39.8, 39.6, 30.3, 20.7, 17.8, 13.2, 12.3; IR
(CHCl3): n = 3401 (OH), 1610 cm±1 (C=O); HRMS: calcd. for
(1R,2S)-1-Phenyl-2-methyl-2-(aminomethyl)-N,N-di-
ethylcyclopropanecarboxamide (9b): Prepared using the
same procedure as described in literature.[4] A mixture of
8b (100 mg, 0.35 mmol) and 10% Pd/C (10 mg) in MeOH
(10 mL) was stirred under 2 atm of hydrogen pressure for
1 h. The catalyst was filtered through a plug of celite. The fil-
trate was evaporated and the residue was purified by col-
umn chromatography on silica gel (CHCl3:MeOH:28%
NH4OH = 90:20:0.5) to give free amine 9 b (yield: 75 mg,
82%); 1H NMR (500 MHz, CDCl3): d = 7.45±7.39 (comp, 2 H),
7.33±7.26 (comp, 2 H), 7.24±7.21 (comp, 1 H), 3.56 (dq,
J = 14.0 Hz, 7.0 Hz, 1 H), 3.47 (dq, J = 14.0 Hz, 7.0 Hz, 1 H),
3.36 (dq, J = 14.0 Hz, 7.0 Hz, 1 H), 3.15 (dq, J = 14.0 Hz,
7.0 Hz, 1 H), 2.89 (d, J = 13.0 Hz, 1 H), 2.54 (d, J = 13.0 Hz,
1 H), 2.20 (br s, 2 H), 1.39 (d, J = 5.0 Hz, 1 H), 1.04 (d,
J = 5.0 Hz, 1 H), 1.03 (t, J = 7.0 Hz, 3 H), 0.86 (s, 3 H), 0.80 (t,
J = 7.0 Hz, 3 H); 13C NMR (125 MHz, CDCl3): d = 170.9, 137.6,
128.8, 128.1, 126.5, 50.6, 41.5, 39.2, 21.5, 18.0, 13.3, 12.3.
The hydrochloride salt of 9 b was obtained by addition of
HCl (1 M solution in ether): mp: 151±153 °C; [a]2D6: ±167.1 (c
0.12, MeOH); 1H NMR (300 MHz, CD3OD): d = 7.43±7.20
(comp, 5 H), 4.78 (br s, 3 H), 3.55±3.11 (comp, 5 H), 2.62 (d,
J = 13.5 Hz, 1 H), 1.70 (d, J = 6.0 Hz, 1 H), 1.29 (d, J = 6.0 Hz,
1 H), 0.95 (t, J = 6.9 Hz, 3 H), 0.75 (s, 3 H), 0.71 (t, J = 6.9 Hz,
3 H); 13C NMR (62.5 MHz, CD3OD): d = 172.9, 137.1, 129.9,
128.8, 49.1, 43.3, 41.8, 40.9, 26.3, 23.4, 18.2, 13.3, 12.5; HRMS:
calcd for C16H25N2O: 261.1967; found: 261.1968.
C16H24NO2: 262.1807; found: 262.1809.
(1R,2S)-1-Phenyl-2-(azidomethyl)-N,N-diethylcyclopro-
panecarboxamide (8a):[4] 1H NMR (250 MHz, CDCl3):
d = 7.35±7.14 (comp, 5 H), 3.62±3.41 (comp, 2 H), 3.37 (d,
J = 7.2 Hz, 2 H), 3.29±3.05 (comp, 2 H), 1.97 (dtd, J = 9.0 Hz,
7.2 Hz, 6.2 Hz, 1 H), 1.57 (dd, J = 6.2 Hz, 5.0 Hz, 1 H), 1.21 (dd,
J = 9.0 Hz, 5.0 Hz, 1 H), 1.13 (t, J = 7.0 Hz, 3 H), 0.66 (t,
J = 7.0 Hz, 3 H); 13C NMR (62.5 MHz, CDCl3): d = 169.0, 140.1,
128.6, 126.6, 126.2, 51.9, 41.7, 39.4, 34.7, 23.6, 19.6, 12.3, 12.2.
(1R,2S)-1-Phenyl-2-methyl-2-(azidomethyl)-N,N-di-
ethylcyclopropanecarboxamide (8b): Prepared using the
same procedure as that described in literature.[4] To a DMF
(5 mL) solution of 7b (104 mg, 0.4 mmol) was added NaN3
(0.52 g, 8.0 mmol), Ph3P (0.63 g, 2.4 mmol), and CBr4
(0.40 g, 1.2 mmol) at 0 °C. The resulting reaction mixture
was allowed to warm to room temperature and stirred for
3 h. Water (10 mL) was added and the resulting mixture
was extracted with ethyl acetate (3 ´ 10 mL). The organic so-
lution was washed with H2O (10 mL) and brine (10 mL),
then dried over anhydrous MgSO4. The residue was purified
by column chromatography on silica gel (hexanes:ethyl
acetate = 5:1) to give 8b as a colorless oil (yield: 113 mg,
99%); [a]2D6:±110.9 (c 3.0, CH2Cl2); 1H NMR (500 MHz,
CDCl3): d = 7.41 (d, J = 7.5 Hz, 2 H), 7.32 (t, J = 7.5 Hz, 2 H),
7.25 (d, J = 7.5 Hz, 1 h ), 3.69 (d, J = 13.0 Hz, 1 H), 3.49 (dq,
J = 14.0 Hz, 7.0 Hz, 1 H), 3.43 (dq, J = 14.0 Hz, 7.0 Hz, 1 H),
3.34 (dq, J = 14.0 Hz, 7.0 Hz, 1 H), 3.25 (d, J = 13.0 Hz, 1 H),
3.18 (dq, J = 14.0 Hz, 7.0 Hz, 1 H), 1.48 (d, J = 5.5 Hz, 1 H),
1.27 (d, J = 5.5 Hz, 1 H), 1.03 (t, J = 7.0 Hz, 3 H),0.86 (s, 3 H),
0.80 (t, J = 7.0 Hz, 3 H); 13C NMR (125 MHz, CDCl3):
d = 169.7, 136.9, 128.8, 128.4, 127.0, 59.3, 41.5, 39.3, 21.9,
Acknowledgements
The support of the National Institutes of Health (GM 46503)
and the National Science Foundation is gratefully acknowl-
edged.
References
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;
HRMS: calcd for C16H22N4O: 287.1872; found: 287.1861.
(1R,2S)-1-Phenyl-2-(aminomethyl)-N,N-diethylcyclo-
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propanecarboxamide (9a):[4] 1H NMR (500 MHz, CDCl3):
d = 7.31±7.16 (comp, 5 H), 3.55 (dq, J = 14.0 Hz, 7.0 Hz, 1 H),
3.48 (dq, J = 14.0 Hz, 7.0 Hz, 1 H), 3.25 (dq, J = 14.0 Hz,
7.0 Hz, 1 H), 3.19 (dq, J = 14.0 Hz, 7.0 Hz, 1 H), 2.80 (dd,
J = 13.0 Hz, 7.5 Hz, 1 H), 2.70 (dd, J = 13.0 Hz, 7.0 Hz, 1 H),
2.18 (br s, 2 H), 1.75 (dddd, J = 8.5 Hz, 7.5 Hz, 7.0 Hz, 6.5 Hz,
1 H), 1.33 (dd, J = 6.5 Hz, 5.0 Hz, 1 H), 1.20 (dd, J = 8.5 Hz,
5.0 Hz, 1 H), 1.11 (t, J = 7.0 Hz, 3 H), 0.69 (t, J = 7.0 Hz, 3 H);
13C NMR (125 MHz, CDCl3): d = 170.0, 140.9, 128.5, 126.0,
125.8, 43.5, 41.5, 39.1, 34.7, 29.4, 19.2, 12.6, 12.2.
302
Adv. Synth. Catal. 2001, 343, 299±302