chromatography (TLC) was carried out using aluminium sheets
pre-coated with silica gel 60F (Merck 5554). Column chromatog-
raphy was carried out using silica gel 60 (Merck 9385, 0.040–
and the organic phase was decanted off and then dried (K
2
CO ),
3
filtered and concentrated in vacuo. GC–MS revealed three major
+
products: 5 [RT = 6.36 min; MS: m/z = 135 (M , 22%), 120
0
.063 mm). Melting points were measured on a Reichert melting
(100%), 93 (8%), 77 (12%)], 4 [RT = 7.19 min; MS: m/z = 135
+
point apparatus equipped with a microscope and are uncorrected.
(M , 21%), 106 (100%), 77 (19%)], 6 [RT = 8.90 min; MS: m/z =
1
13
+
H NMR (300 MHz) and C NMR (75 MHz) spectra were
recorded on a Varian instrument. Samples were dissolved in CDCl
151 (M , 12%), 120 (100%), 93 (6%), 77 (16%)]. The amines 4 and 5
3
were isolated from the aminoalcohol 6 by column chromatography
purchased from Cambridge Isotope Labs. Gas chromatography–
mass spectrometry (GC–MS) was performed on an HP 5890
Gas chromatograph/5972 Mass Selective Detector or an HP
(SiO
2
, CH
2
Cl –EtOAc 1 : 1), and the product assignment was then
2
1
confirmed by H NMR spectroscopy.
6
890 Gas chromatograph/5973 Mass Selective Detector; RT =
Entries 2–5, Table 1. The amide 1 in THF was added to a
retention time. Fast atom bombardment (FAB) spectra were
obtained on a Jeol JMS-HX 110 Tandem Mass Spectrometer in the
positive ion mode using 3-nitrobenzyl alcohol (NBA) as matrix.
Microanalyses were performed at the Microanalytical Laboratory
at the Department of Chemistry, University of Copenhagen.
suspension (entry 2) or solution (1 M, entries 3–5) of LiAlH in
4
THF. The addition was performed under inert atmosphere. The
concentration of amide was the same in entries 2–5 after complete
addition (1.85 g in a total of 52 mL THF for entry 2; 1.84 g in a
total of 50 mL THF for entries 3–5). The mixture was hydrolyzed
with conc. aqueous NaOH (ca. 5 mL) (Caution), and the mixture
stirred for 1 h. To the resulting gel was added another portion of
Synthesis of 1-(phenylcarbamoyl)ethyl acetate (9)
Et
of Na
2
O (100 mL), and the organic phase was filtered through a layer
SO and concentrated in vacuo.
To a solution of 2-chloro-N-phenylpropanamide 1 (5.46 g,
2
4
2
3
9.7 mmol) in DMF (60 mL) was added NaOAc (2.95 g,
6.0 mmol). The mixture was refluxed overnight, whereupon the
Reduction of 1-(phenylcarbamoyl)ethyl tosylate (2). Performed
(1 M) in THF.
precipitate was filtered off and washed with DMF. The filtrate was
concentrated at reduced pressure using an oil pump. The residue
in a similar way, using a solution of LiAlH
4
was subjected to column chromatography (SiO
2
, 5% MeOH in
Reduction of 2-methyl-N-phenylaziridine (3). Performed in a
CH Cl ) to provide the product (5.3 g, 86%) as white solid. Mp
2
2
similar way, using a solution of LiAlH (1 M) in THF and the
additive given in Table 2.
4
◦
1
1
3
1
20–121 C. H NMR (300 MHz, CDCl
3
): d = 1.57 (d, J = 7.5 Hz,
H), 2.21 (s, 3 H), 5.34 (q, J = 7.5 Hz, 1 H), 7.14 (t, J = 7.9 Hz,
H), 7.34 (t, J = 7.9 Hz, 2 H), 7.54 (d, J = 8.2 Hz, 2 H), 7.81
1
3
References
(
s, 1 H). C NMR (75 MHz, CDCl
3
): d = 18.0, 21.4, 71.2, 120.3,
+
1
25.1, 129.3, 137.2, 168.4, 169.7. MS(FAB): m/z = 207 (M ).
1
A. Uffer and E. Schlittler, Helv. Chim. Acta, 1948, 31, 1397–1400.
2 K. Suzuki, K. Okano, K. Nakai, Y. Terao and M. Sekiya, Synthesis,
983, 723–725.
A. Hassner, G. J. Matthews and F. W. Fowler, J. Am. Chem. Soc., 1969,
1, 5046–5054.
4 N. De Kimpe, R. Verh e´ , L. De Buyck and N. Schamp, J. Org. Chem.,
980, 45, 5319–5325.
5 N. De Kimpe, R. Verh e´ , L. De Buyck and N. Schamp, J. Org. Chem.,
981, 46, 2079–2081; N. De Kimpe, R. Verhe, L. De Buyck and N.
Found: C, 63.67; H, 6.26; N, 6.70. C11
H, 6.32; N, 6.76%.
H
13NO requires C, 63.76;
3
1
3
9
Synthesis of 2-hydroxy-N-phenylpropanamide (8)
1
To a suspension of compound 9 (735 mg, 3.55 mmol) in
1
dioxane (40 mL) was added Na
20 mL). The mixture was refluxed overnight. After cooling to
room temperature, the mixture was extracted with Et
O (3 ×
0 mL). The combined organic phase was dried (Na SO ), filtered,
2
CO
3
(5.31 g, 50.1 mmol) in H
2
O
Schamp, Bull. Soc. Chim. Belg., 1983, 92, 233–239.
N. De Kimpe, R. Verh e´ and N. Schamp, Bull. Soc. Chim. Belg., 1975,
84, 701–707.
(
6
2
2
2
4
7 N. De Kimpe, R. Verh e´ , L. De Buyck and N. Schamp, Recl. Trav. Chim.
Pays-Bas, 1977, 96, 242–246.
and concentrated in vacuo. Drying at oil pump provided the
analytically pure product as white crystals in nearly quantitative
8
9
K. Ichimura and M. Ohta, Bull. Chem. Soc. Jpn., 1967, 40, 432.
K. Ichimura and M. Ohta, Bull. Chem. Soc. Jpn., 1970, 43, 1443–1450.
◦
1
yield. Mp 50–52 C. H NMR (300 MHz, CDCl
3
): d = 1.53 (d, J =
10 J. Cleophax, J. Hildesheim, A.-M. Sepulchre and S. D. G e´ ro, Bull. Soc.
Chim. Fr., 1969, 153–156.
6
8
8
1
6
8
.9 Hz, 3 H), 2.55 (s, 1 H), 4.37 (q, J = 6.9 Hz, 1 H), 7.12 (t, J =
1
1 K. Kitahonoki, K. Kotera, Y. Matsukawa, S. Miyazaki, T. Okada,
H. Takahashi and Y. Takano, Tetrahedron Lett., 1965, 6, 1059–1065;
K. Kotera, T. Okada and S. Miyazaki, Tetrahedron, 1968, 24, 5677–
5690; K. Kotera, Y. Matsukawa, H. Takahashi, T. Okada and K.
Kitahonoki, Tetrahedron, 1968, 24, 6177–6184; K. Kotera, S. Miyazaki,
H. Takahashi, T. Okada and K. Kitahonoki, Tetrahedron, 1968, 24,
.2 Hz, 1 H), 7.33 (t, J = 8.2 Hz, 2 H), 7.56 (d, J = 8.2 Hz, 2 H),
1
3
.44 (s, 1 H). C NMR (75 MHz, CDCl
3
): d = 21.4, 69.1, 119.9,
+
24.7, 129.2, 137.3, 172.4. MS(FAB): m/z = 165 (M ). Found: C,
5.40; H, 6.65; N, 8.45. C
.48%.
9
H
11NO requires C, 65.44; H, 6.71; N,
2
3
1
681–3696; H. Tanida, T. Okada and K. Kotera, Bull. Chem. Soc. Jpn.,
973, 46, 934–938.
1
1
2 K. Kotera, Y. Takano, A. Matsuura and K. Kitahonoki, Tetrahedron,
970, 26, 539–556.
Reduction of 2-chloro-N-phenylpropanamide (1)
1
3 J. L. Pierre, H. Handel and P. Baret, Tetrahedron, 1974, 30, 3213–3223;
P. Baret, P. M. Bourgeois, C. Gey and J. L. Pierre, Tetrahedron, 1979, 35,
Entry 1, Table 1. To a solution of the amide 1 (9.15 g,
2
4
9.8 mmol) prepared according to Suzuki in Et
2
O (100 mL)
1
89–196; J. M. Concell o´ n, J. R. Su a´ rez, S. Garc ´ı a-Granda and M. R.
was added LiAlH
reaction mixture on an ice bath under an inert atmosphere. Then
the mixture was refluxed for 20 h, cooled, and diluted with Et
4
(5.70 g, 150 mmol) over 1 h, cooling the
D ´ı az, Angew. Chem., Int. Ed., 2004, 43, 4333–4336; L. Yu, A. Kokai
and A. K. Yudin, J. Org. Chem., 2007, 72, 1737–1741.
4 D. Tanner, H. M. He and P. Somfai, Tetrahedron, 1992, 48, 6069–6078;
D. Tanner and P. Somfai, Tetrahedron Lett., 1987, 28, 1211–1214; D.
Tanner and T. Groth, Tetrahedron, 1997, 53, 16139–16146; D. Tanner
and O. R. Gautun, Tetrahedron, 1995, 51, 8279–8288.
1
2
O
(
55 mL), and hydrolyzed with aqueous 10% NaOH (ca. 50 mL).
To the resulting gel was added another portion of Et O (100 mL),
2
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