4
06
O. Josse et al.
SHORT PAPER
3
-(N-tert-Butoxycarbonyl)aminopropanethioacyl N-Phthalim-
After evaporation under vacuum, the residue was dissolved in
ide (7)
CH Cl (20 mL) and extracted with H O (3 × 7 mL, HPLC grade).
2
2
2
To a mixture of 6 (2.5 g, 12.2 mmol) and K CO (2.029 g,
Lyophilization of the aqueous phases gave pure 8 (trifluoroacetate
salt) as a yellow amorphous solid; yield: 1.405 g (95%); mp 60.2Ð
61.2¡C.
2
3
1
4.7 mmol) in THF (30 mL), cooled at 0¡C, was added dropwise
(within 4 h, stirring under argon atmosphere) a solution of phthaloyl
dichloride (2.11 mL, 14.7 mmol) in THF (30 mL). After the addi-
tion was complete, the mixture was further stirred for 3 h at 20¡C,
1
H NMR (D O, 300 MHz): d = 1.10 (t, 3 H, J = 7.5 Hz, SCH CH ),
2
2
3
3
.07 (q, 2 H, J = 7.5 Hz, SCH CH ), 3.15 (t, 2 H, J = 6.2 Hz,
2 3
then poured into H O (50 mL) and extracted with EtOAc (3 × 15
2
CH CS Et), 3.29 (t, 2 H, J = 6.2 Hz, CH NH ).
2
2
2
2
mL). Drying (MgSO ), concentration and purification by flash
4
13
C NMR (D O, 50 MHz): d = 12.17 (SCH CH ), 31.79
chromatography on silica gel (EtOAc/hexane, 30:70; R 0.72 for
2
2
3
f
(
2
(
SCH CH ), 39.87 (CH CS Et), 47.61 (CH NH ), 117.18 (q, J =
EtOAc/hexane, 50:50) gave pure 7 as an amorphous red solid;
yield: 2.660 g (65%). No melting point could be determined due to
decomposition.
2 3 2 2 2 2
88.7 Hz, CF CO H), 163.59 (q, J = 35.4 Hz, CF CO H), 235.38
3 2 3 2
CS Et).
2
1
IR (KBr): n = 3000Ð2600, 1670 (C=O, carboxylate salt), 1522Ð
H NMR (CDCl /TMS, 200 MHz): d = 1.39 (s, 9 H, t-C H ), 3.48
3
4
9
+
Ð1
1
539 (NH ), 1456, 1435, 1136, 1196, 910, 839, 798, 723 cm .
(
t, 2 H, J = 5.7 Hz, CH CSNphth), 3.63 (dt, 2 H, J = 5.7, 6.1 Hz,
3
2
CH NHBoc), 4.95 (br t, 1 H, NH), 7.83Ð7.88 (m, 2 H
8
), 7.96Ð
+
2
arom
MS (FAB/glyc.): m/z (%) = 150.0 (MH , 73.6), 133.0 (100), 121.0
.01 (m, 2 Harom).
(46.3), 105.0 (17.3), 87.0 (19.8), 58.9 (28.8), 29.8 (28.0).
13
C NMR (CDCl /TMS, 50 MHz): d = 28.21 [(CH ) C], 38.61
+
3
3 3
HRMS (FAB): m/z calcd for C H NS (MH without counter-ion)
5
11
2
(
1
(
CH CSNphth), 49.33 (CH NHBoc), 79.32 [(CH ) C], 124.57,
2 2 3 3
150.0411, found 150.0411.
30.66, 135.39, 155.68 (OCONH), 164.54 (phth-C=O), 209.91
C=S).
Anal. Calc. for C H F NO S : C 31.93; H 4.59; N 5.32; S 24.35.
7
12
3
2 2
Found: C 31.98; H 4.49; N 5.23; S 23.97.
IR (KBr): n = 3349 (NH), 2970, 1724 (C=O, Ft), 1684 (OCONH),
1
Ð1
531, 1456, 1367, 1319, 1252, 1163, 1014, 872 cm .
Acknowledgement
MS (CI/CH -N O): m/z (%) = 333.0 ([M Ð H]Ð, 43.2), 185.9 (5.0),
4
2
1
46.9 (15.0), 145.9 (100).
This work was supported by the Fonds National de la Recherche
ScientiÞque (F.N.R.S., Belgium), the Fonds J. Maisin (U.C.L., Bel-
gium) and the Fonds pour la Formation ˆ la Recherche dans
lÕIndustrie et lÕAgriculture (F.R.I.A., Belgium).
+
HRMS (FAB): m/z calcd for C H N O S (MH ) 335.1066, found
1
6
19
2
4
3
35.1070.
Ethyl 3-(N-tert-Butoxycarbonyl)aminopropanedithioate (3)
To a cold (0¡C) solution of 7 (2.6 g, 7.7 mmol) in CH Cl (25 mL),
were added dropwise successively (stirring under argon atmo-
2
2
References
sphere) ethanethiol (2.88 mL, 38.8 mmol) and Et N (1.081 mL,
(1) Metzner P. Phosphorus, Sulfur, Silicon 1991, 59, 1.
(2) Metzner P. Synthesis 1992, 1185.
(3) Ramadas, S. R.; Srinivasan, P. S.; Ramachandran, J.; Sastry,
3
7
.7 mmol). The mixture was allowed to reach 20¡C within 1 h and
left for another 1 h at 20¡C. After addition of 4 N NaOH (75 mL),
the mixture was rapidly extracted with CH Cl (3 × 25 mL). Drying
V.V.S.K. Synthesis 1983, 605.
2
2
(
MgSO ), concentration and purification by flash chromatography
(4) Voss, J. Comprehensive Organic Synthesis, Trost, B. M.;
Fleming, F., Eds.; Pergamon Press: Oxford, 1991, Vol 6, Chap
2.5, p 453.
4
on silica gel (EtOAc/hexane, 10:90; R 0.75 for EtOAc/hexane,
f
3
0:70), gave pure 3 as a yellow oil; yield: 1.452 g (75%).
1
(5) Cava, M. P.; Levinson, M. I. Tetrahedron 1985, 41, 5061.
H NMR (CDCl /TMS, 300 MHz): d = 1.32 (t, 3 H, J = 7.5 Hz,
3
(6) Pedersen, B.S.; Scheibye, S.; Clausen, K.; Lawesson, S.-O.
SCH CH ), 1.44 (s, 9 H, t-C H ), 3.16 (t, 2 H, J = 6.3 Hz,
CH CS Et), 3.22 (q, 2 H, J = 7.5 Hz, SCH CH ), 3.57 (dt, 2 H, J =
6
2
3
4
9
Bull. Soc. Chim. Belg. 1978, 87, 293.
2
2
2
3
(
(
7) Poupaert, J.; Bruylants, A.; Crooy, P. Synthesis 1972, 622.
8) Storer, A. C.; Ozaki, Y.; Carey, P. R. Can. J. Chem. 1982, 60,
.0, 6.3 Hz, CH NHBoc), 4.90 (br t, 1 H, J = 6.0 Hz, NHBoc).
2
13
C NMR (CDCl /TMS, 50 MHz): d = 11.96 (SCH CH ), 28.25
3
2
3
1
99.
[
(
(CH ) C], 30.58 (SCH CH ), 40.55 (CH CS Et), 51.03
3 3 2 3 2 2
(9) Kohrt, A.; Hartke, K. Liebigs Ann. Chem. 1992, 595.
CH NHBoc), 79.21 [(CH ) C], 155.62 (OCONH), 235.61 (CS Et).
2
3 3
2
(
10) Neugebauer, W.; Pinet, E.; Kim, M.; Carey, P. R. Can. J.
IR (Film): n = 3353 (NH), 2975, 1699 (OCONH), 1507, 1456,
Chem. 1996, 74, 341.
(11) Clausen, K.; Thorsen, M.; Lawesson, S.-O. J. Chem. Soc.,
Perkin Trans. 1 1984, 785.
12) Hartke, K.; Barrmeyer, S. J. Prakt. Chem. 1996, 338, 251.
13) Nozaki, S.; Muramatsu, I. Bull. Chem. Soc. Jpn. 1988, 61,
2647.
Ð1
1
365, 1250, 1168, 911 cm .
MS (CI/CH -N O): m/z (%) = 248.0 ([M Ð H]Ð, 100), 186.0 (10.7),
4
2
(
(
1
30.9 (9.1), 118.9 (19.8), 115.9 (78.6), 41.8 (34.0).
Anal. Calc. for C H NO S : C 48.16; H 7.68; N 5.62; S 25.71.
1
0
19
2 2
Found: C 48.24; H 7.72; N 5.74; S 25.63.
(
14) Brain, C. T.; Hallett, A.; Ko, S. Y. J. Org. Chem. 1997, 62,
3
808.
Ethyl 3-Aminopropanedithioate (8)
(15) Brain, C. T.; Hallett, A.; Ko, S. Y. Tetrahedron Lett. 1998, 39,
The dithioester 3 (1.4 g, 5.6 mmol) was dissolved in cold (0¡C) tri-
fluoroacetic acid (10 mL) and left 1 h under an argon atmosphere.
127.
Synthesis 1999, No. 3, 404–406 ISSN 0039-7881 © Thieme Stuttgart · New York