Arora et al.
mass spectrum (FAB), theory for (C9H9O4P) M + Na 235.0131,
found 235.0130.
tert-Butyl 3-Acetamidopropylcarbamate 23. 1H NMR (CDCl3)
δ 6.57 (br t, 1H, NH), 5.14 (br t, 1H, NH), 3.27 (q, J ) 6 Hz, 2H,
CH2), 3.16 (q, J ) 6 Hz, 2H, CH2), 1.99 (s, 3H, CH3),1.61 (q, J )
6 Hz, 2H, CH2), 1.44 (s, 9H, CH3); 13C NMR (CDCl3) δ 170.8,
156.9, 79.4, 37.2, 36.1, 30.2, 28.4, 23.4; high resolution mass
spectrum (FAB), theory for (C14H17O3N) M + H 217.1547, found
217.1540 (also theory for M + Na 239.1366, found 239.1374).
(S)-O-Benzoyl-N-(1-phenylethyl)hydroxylamine 24. A solution
of benzoyl peroxide (BPO, 8.25 mmol) in CH2Cl2 (5 mL/mmol
BPO) was added quickly to a mixture of S-(1-phenylethyl) amine
(8.25 mmol) and a pH 10.5 buffer solution (5 mL/mmol amine) at
room temperature. TLC was used to monitor the consumption of
starting material. After the reaction was complete, the aqueous
layer was extracted twice with CH2Cl2. The organic layers were
combined, dried over anhydrous Na2SO4, filtered, and concen-
trated to give the crude product, which was subjected to flash
column chromatography with 70% CH2Cl2/hexane. Yield 75%;
Rf 0.34 (7:3; CH2Cl2:hexane); 1H NMR (CDCl3) δ 7.90 (m, 2H,
CH), 7.45-7.21 (m, 8H, CH), 4.29 (q, J ) 6.5 Hz, 1H, CH),
1.48 (m, 3H, CH3); 13C NMR (CDCl3) δ 166.7, 133.3, 129.3,
128.6, 128.5, 127.9, 127.1, 60.9, 19.8; high resolution mass
spectrum (FAB), theory for (C14H17O3N) M + H 242.1176, found
242.1176 (also theory for M + Na 264.0995, found 264.1012).
Anal. Calcd. theory for (C15H15NO2): C, 74.67; H, 6.27; N, 5.81.
Found: C, 74.55; H, 6.34; N, 5.63.
General Procedure for Coupling of r-Keto Phosphonic
Acids with N-Benzoyloxyamines. The N-Benzoyloxyamine (0.13
mmol) and the R-ketophosphonic acid or its derivative (0.27 mmol)
were dissolved in tert-butyl alcohol and water (1:1 v/v, 5 mL). The
solution was heated to 40 °C for 15 h and the solvent was removed
under high vacuum. The oily residue was dissolved in CH2Cl2 (10
mL) and washed with aq Na2CO3 (10 mL). The organic layer was
separated, dried over anhydrous Na2SO4, filtered, and concentrated
to provide the crude reaction mixture. The required amide was
purified either by column chromatography or by preparative TLC.
The amides 3a, 3b, 20, 21, 22, and 23 were synthesized by using
the above method. Of these, the amides 3a,7 3c,17 20,18 and 2119
are known and their spectral data matched the literature values.
Beyond the NMR spectra shown in the Supporting Information for
21, a high resolution mass spectrum was obtained for compound
21: (FAB) theory for (C12H15O3N) M + Na 244.0944, found
244.0962. Elemental Anal. for 21, theoretical for C12H15O3N: C,
65.14; H, 6.83; N, 6.33. Found: C, 64.91; H, 6.93; N, 6.33.
3-Acetylaminopropionic Acid Ethyl Ester 20. 1H NMR
(CDCl3) δ 6.15 (br s, 1H, NH), 4.15 (q, J ) 7.2 Hz, 2H, OCH2),
3.52 (q, J ) 6 Hz, 2H, NCH2), 2.53 (t, J ) 6 Hz, 2H, NCH2), 1.96
(s, 2H, PhCH2), 1.27 (t, J ) 7.2 Hz, 3H, CH3); 13C NMR (CDCl3)
δ 171.5, 168.8, 59.6, 33.8, 32.9, 22.3, 13.1; IR (CDCl3): 1727, 1675,
1194 cm-1; high resolution mass spectrum (FAB), theory for
(C7H13N1O3) M + H 160.0968, found M + 1 160.0981. Anal.
Calcd. theory for (C7H13N1O3 ·0.2H2O): C, 51.65; H, 8.30; N, 8.60.
Found: C, 51.55; H, 8.43; N, 8.47.
Competition Experiment with 4b and 24. The N-Benzoy-
loxyamines 4b (0.34 mmol) and 24 (0.34 mmol) and the R-keto-
phosphonic acid disodium salt 10 (0.68 mmol) were dissolved in
tert-butyl alcohol and water (1:1 v/v, 5 mL). The solution was
heated to 40 °C for 15 h and the solvent was removed under high
vacuum. The oily residue was dissolved in CH2Cl2 (10 mL) and
washed with aq Na2CO3 (10 mL). The organic layer was separated,
dried over anhydrous Na2SO4, filtered, and concentrated to provide
the crude reaction mixture. Dibenzyl ether (100 µL) was added as
3-(3-Phenylacryloylamino)propionic Acid Ethyl Ester 22. 1H
NMR (CDCl3) δ 7.63 (d, J ) 16 Hz, 1H, CH), 7.50 (m, 2H, ArH),
7.36 (m, 3H, ArH), 6.38 (d, J ) 16 Hz, 1H, CH), 6.35 (br s, 1H,
NH), 4.18 (q, J ) 7 Hz, 2H, CH2), 3.66 (q, J ) 6 Hz, 2H, CH2),
2.62 (t, J ) 6 Hz, 2H, CH2), 1.28 (t, J ) 7 Hz, 3H, CH3); 13C
NMR (CDCl3) δ 170.4, 163.2, 138.6, 132.2, 127.1, 126.6, 125.2,
1
an internal standard and the H NMR spectrum was recorded to
118, 58.3, 32.4, 31.4, 11.6; IR (CDCl3) 1725, 1670, 1203 cm-1
;
determine the percent yield of the product formed (via relative
integration).
high resolution mass spectrum (FAB), theory for (C14H17O3N) M
+ H 248.1281, found 248.1288 (also theory for M + Na 270.1101,
found 270.1116).
1
Supporting Information Available: H NMR for 1a, 1b,
3a, 3c, 4, 5b, 8, 16, 17, 18, 19, 20, 21, 22, 23, and 24 in CDCl3
and R-ketophosphonic acids 9, 10, 11, 12, and 13 in D2O and
13C NMR spectra of the new compounds 13 (D2O), 22 (CDCl3),
23 (CDCl3), and 24 (CDCl3). This material is available free of
(17) Yoo, W. J.; Li, C. J. Highly Efficient Oxidative Amidation of Aldehydes
with Amine Hydrochloride Salts. J. Am. Chem. Soc. 2006, 128, 13064–13065.
(18) Li, X.-G.; Kanerva, L. T. Lipases in ꢀ-Dipeptide Synthesis in Organic
Solvents. Org. Lett. 2006, 8, 5593–5596.
(19) Katritzky, A. L.; Strah, S.; Belyakov, S. A. The Preparation of
Functionalized Amines and Amides Using Benzotriazole Derivatives and
Organozinc Reagents. Tetrahedron 1998, 54, 7167–7178.
JO800223J
6186 J. Org. Chem. Vol. 73, No. 16, 2008