Helvetica Chimica Acta – Vol. 89 (2006)
357
980 mg (37%). IR: 3288s (br.), 2971s, 1738vs, 1711vs, 1471w, 1378s, 1356m, 1244s, 1094s, 1040s, 925w. 1H-
NMR: 0.97 (s, Me2C); 1.59–1.71 (m, CH2); 1.99 (s, MeCO); 2.21 (s, CH2); 4.01 (br. s, CH2O); 10.41 (br. s,
COOH). 13C-NMR: 20.7 (q, MeCO); 27.2 (q, Me2C); 32.0 (s, Me2C), 37.6, 43.9 (2t, 2 CH2); 66.6 (t, CH2O);
171.1 (s, C=O); 177.3 (s, COOH). ESI-MS: 211 (100, [M+Na]+).
4. 4-[1-Methyl-1-(N-methyl-N-phenylcarbamoyl)ethylcarbamoyl]-3,3-dimethylbutyl Acetate (10). To
a soln. of 8 (376 mg, 2 mmol) in dry THF (20 ml), 9 (365 mg, 2.1 mmol) was added. The mixture was stir-
red at r.t. overnight, and the solvent was evaporated i.v., CC (CH2Cl2/MeOH 40 :1) yielded 622 mg (86%)
of 10. Colorless powder. M.p. 98.1–99.48. 1H-NMR: 0.97, 1.41 (2s, 2 Me2C); 1.62 (t, J=7.1, CH2); 1.99 (s,
MeCO); 2.08 (s, CH2); 3.19 (s, MeN); 3.10 (t, J=7.1, CH2O); 6.55 (s, NH); 7.20–7.39 (m, 5 arom. H). 13C-
NMR: 20.8 (q, MeCO); 26.3, 27.0 (2q, 2 Me2C); 33.0 (s, Me2C); 41.3 (t, CH2); 42.3 (q, MeN); 48.2 (t, CH2);
58.1 (s, Me2C); 68.7 (t, CH2O); 127.8, 128.0, 129.3 (3d, 5 arom. CH); 144.6 (s, arom. C); 169.8, 171.6, 173.2
(3s, 3 C=O). ESI-MS: 385 (100, [M+Na]+]).
5. 5-Hydroxy-3,3-dimethyl-N-[1-methyl-1-(N-methyl-N-phenylcarbamoyl)ethyl]pentanamide (11). A
soln. of 9 (362 mg, 1 mmol) in THF/H2O 2 :1 (20 ml) was treated with 4 equiv. of LiOH at r.t. for 4 h.
Evaporation of the solvent i.v., extraction of the residue with CH2Cl2, drying (MgSO4), evaporation
i.v., and washing with Et2O yielded 11, which was used without further purification. Yield: 298 mg
1
(93%) of 11. White solid. M.p. 128.4–126.08. H-NMR: 0.99, 1.46 (2s, 2 Me2C); 1.60 (t, J=7.1, CH2);
2.00 (s, CH2); 3.17 (s, MeN); 3.18 (t, J=7.1, CH2O); 6.51 (s, NH); 7.18–7.36 (m, 5 arom. H). 13C-
NMR: 26.4, 28.8 (2q, 2 Me2C); 32.8 (s, Me2C); 41.4 (t, CH2); 42.4 (q, MeN); 48.2 (t, CH2); 58.2 (s,
Me2C); 69.7 (t, CH2O); 127.8, 128.0, 129.3 (3d, 5 arom. CH); 144.5 (s, arom. C); 171.7, 173.3 (2s,
2 C=O). ESI-MS: 343 (100, [M+Na]+).
6. 2-[(5-Chloro-3,3-dimethylpentanoyl)amino]-2-methylpropanoic Acid (12). A suspension of 11 (80
mg, 0.25 mmol) in dry toluene (30 ml) was heated to 1008, and HCl gas was bubbled through the suspen-
sion for 4–6 min. Then, the mixture was allowed to cool to r.t. while bubbling N2 through it (ca. 20 min).
The solvent was evaporated, and the white residue was washed with CH2Cl2 (3×15 ml) and dried in h.v.:
36 mg (59%) of 12. M.p. 118.9–121.08. IR: 3320vs, 2980s, 1722vs, 1620s, 1561s, 1466s, 1428s, 1389m,
1
1246m, 1232m, 1166s, 1092m, 1051w, 945w. H-NMR ((D6)DMSO): 0.97, 1.33 (2s, 2 Me2C); 1.68–1.79
(m, CH2); 1.97 (s, CH2); 3.60–3.69 (m, CH2Cl); 7.82 (br. s, NH); 11.81 (br. s, COOH). 13C-NMR
((D6)DMSO): 24.8, 27.2 (2q, 2 Me2C); 33.4, 42.5 (2t, 2 CH2); 54.6 (t, CH2Cl); 55.7 (s, Me2C); 169.9,
175.4 (2s, 2 C=O). ESI-MS: 274 (25, [M(37Cl)+Na]+), 272 (100, [M(35Cl)+Na]+), 214 (10, [MÀCl]+).
7. X-Ray Crystal-Structure Determination of 12 (Table and Figs. 1 and 2)3). All measurements were
performed on a Nonius KappaCCD area-detector diffractometer [15] using graphite-monochromated
MoKa radiation (l 0.71073 Å) and an Oxford Cryosystems Cryostream 700 cooler. The data collection
and refinement parameters are given in the Table, and views of the molecules are shown in Figs. 1 and
2. Data reduction was performed with HKL Denzo and Scalepack [16]. The intensities were corrected
for Lorentz and polarization effects, and an absorption correction based on the multi-scan method
[17] was applied. Equivalent reflections, other than Friedel pairs, were merged. The structure was solved
by direct methods using SIR92 [18], which revealed the positions of all non-H-atoms. The non-H-atoms
were refined anisotropically. The OH and amide H-atoms were placed in the positions indicated by a dif-
ference electron-density map, and their positions were allowed to refine together with individual iso-
tropic displacement parameters. All remaining H-atoms were placed in geometrically calculated posi-
tions and refined using a riding model where each H-atom was assigned a fixed isotropic displacement
parameter with a value equal to 1.2Ueq of its parent C-atom (1.5Ueq for the Me groups). Refinement
of the structure was carried out on F2 using full-matrix least-squares procedures, which minimized the
function Sw(Fo2 –Fc2)2. A correction for secondary extinction was applied. Refinement of the absolute
structure parameter [19][20] yielded a value of 0.01(6), which confirms that the refined model represents
the true absolute structure. Neutral atom scattering factors for non-H-atoms were taken from [21], and
3
)
CCDC-286116 contains supplementary crystallographic data for this paper. These data can be
obtained free of charge form the Cambridge Crystallographic Data Centre (CCDC), via http://