13C NMR (75 MHz, CDCl3): δ 14.9, 17.5, 27.6, 45.9, 63.8, 74.4,
117.6, 127.9, 127.9, 128.8, 159.1. HRMS calcd for C15H19NO2,
245.1416; found, 245.1415.
dicyclohexylurea. After this had stirred at room temperature for
15 min, the resulting solution of the MTPA anhydride was filtered
through a pipet capped with cotton wool and added to samples of
(R)-12 (50 mg, 0.19 mmol). The resulting clear colorless solutions
were stirred at room temperature for 20 h and then quenched with
satd aqueous NaHCO3 (3 mL). The reaction mixture was extracted
with CHCl3 (3 × 5 mL). The combined organic layers were washed
with brine and dried over Na2SO4. The solvent was evaporated,
and the residue was chromatographed on silica gel (hexane/EtOAc
) 4:1) to give compound 12 (79 mg, 87%) as an oil, with care
being taken not to exercise a mechanical separation of one of the
Methyl 3-Benzyl-4-isopropyl-2-oxooxazolidine-5-carboxylate
(7). To a solution of acid 6 (1.4 g, 5.3 mmol) in DMF (26 mL)
was added K2CO3 (1.5 g, 10.6 mmol) and CH3I (0.7 mL, 10.6
mmol) at 0 °C. After being stirred for 2 h at room temperature, the
reaction mixture was added to a mixture of EtOAc (10 mL) and 1
N HCl (5 mL). The reaction mixture was extracted with EtOAc (3
× 15 mL), and the combined organic layers were washed with brine
and dried over Na2SO4. The solvent was evaporated, and the residue
was chromatographed on silica gel (hexane/ EtOAc ) 2/1) to give
compound 7 (1.25 g, 85%) as an oil. IR (KBr): 3252, 2954, 1755,
1
diastereoisomers over the other. H NMR (500 MHz, CDCl3): δ
0.88 (m, 6H), 1.43 (s, 10 H), 3.55 (s, 3H), 3.69 (s, 3H), 3.94 (m,
1H), 4.52 (d, 1H, J ) 10.3 Hz), 5.34 (s, 1H), 7.45 (m, 3H), 7.70
(m, 2H). 13C NMR (125 MHz, CDCl3): δ 19.7, 19.8, 28.6, 30.4,
53.0, 56.1, 74.2, 80.1, 127.9, 128.8, 130.2, 132.4, 155.7, 166.4,
168.6. 19F NMR (473 MHz, CDCl3): -72.08 {s (>99%), CF3},
-72.48 {s (<1%), CF3}.
1
1586 cm-1. H NMR (300 MHz, CDCl3): δ 0.74∼0.91 (6H, m),
2.06 (1H, m), 3.50 (1H, t, J ) 3.6 Hz), 4.05 (1H, d, J ) 15.3 Hz),
4.60 (1H, d, J ) 3.1 Hz), 4.91 (1H, d, J ) 15.3 Hz), 7.25∼7.63
(5H, m). 13C NMR (75 MHz, CDCl3): δ 14.8, 17.5, 28.0, 46.2,
52.9, 62.3, 71.1, 127.9, 128.1, 128.9, 135.3, 157.0, 170.0. HRMS
calcd for C15H19NO4, 277.1314; found, 277.1315.
(2S,3S)-3-Amino-2-hydroxy-isopentanoic Acid (2). To a solu-
tion of 10 (80 mg, 0.10 mmol) in 95% EtOH (1.5 mL) was added
4 N KOH (1.5 mL). The reaction mixture was refluxed for 12 h,
cooled to room temperature, and then quenched with 10% HCl (3
mL), filtered, and evaporated. The residue was dissolved in MeOH
(3 mL) without further purification and mixed with Dowex 50W-
X8 (1 g). The mixture was filtered and then washed with MeOH.
The remaining residue was diluted with 3 N NH4OH solution. The
solution was evaporated and then coevaporated with toluene to give
Methyl 4-Isopropyl-2-oxooxazolidine-5-carboxylate (8). To a
solution of compound 7 (0.8 g, 2.88 mmol) in Et2O (3 mL) was
slowly added a solution of Li (80 mg, 11.5 mmol) in liquid ammonia
(8 mL) at -70 °C under argon. After being stirred for 5 min at the
same temperature, it was quickly quenched with water (10 mL).
The reaction mixture was extracted with EtOAc (3 × 8 mL), and
the combined organic layers were washed with brine and dried over
Na2SO4. The solvent was evaporated, and the residue was chro-
matographed on silica gel (hexane/ EtOAc ) 1/1) to give compound
compound 2 (15 mg, 82%) as a solid. Mp 215-216 °C; [R]20
D
1
8 (0.41, 76%) as an oil. IR (KBr): 2954, 2504, 1755 cm-1. H
+19.2 (c 0.5, MeOH). IR (KBr): 2986, 1768, 1641 cm-1. 1H NMR
(300 MHz, D2O): δ 0.87 (6H, m), 2.02 (1H, m), 3.82 (1H, t, J )
3.4 Hz), 4.51 (1H, d, J ) 3.4 Hz). 13C NMR (75 MHz, D2O): δ
18.3, 19.6, 29.2, 49.5, 70.4, 174.4. HRMS calcd for C6H13NO3,
147.0895; found, 147.0892.
NMR (300 MHz, CDCl3): δ 0.89∼0.94 (6H, m), 2.08 (1H, m),
3.49 (1H, t, J ) 3.5 Hz), 3.76 (3H, s), 4.07 (1H, d, J ) 15.3 Hz),
4.60 (1H, d, J ) 3.6 Hz), 4.98 (1H, d, J ) 15.2 Hz), 7.25∼7.45
(5H, m). 13C NMR (75 MHz, CDCl3): δ 14.7, 17.5, 28.0, 46.2,
52.8, 62.3, 71.1, 127.9, 128.1, 128.8, 135.9, 157.0, 170.0. HRMS
calcd for C8H13NO4, 187.0845; found, 187.0792.
(2R,3S)-3-Amino-2-hydroxy-isopentanoic Acid (1). Compound
9 was hydrolyzed with 4 N KOH in 95% EtOH (1.5 mL) for 10 h,
using the same procedure as compound 2. The residue was
hydrogenated with 20% Pd(OH)2/C (10 mg) in MeOH (2 mL) at
room temperature for 12 h. The reaction mixture was filtered and
evaporated. The residue was dissolved in MeOH (3 mL) and mixed
with Dowex 50W-X8 (1 g). The mixture was filtered and then
washed with MeOH. The remaining residue was diluted with 3 N
NH4OH solution. The solution was evaporated and then coevapo-
rated with toluene to give compound 1 (18 mg, 62%) as a solid.
(4S,5R)-Methyl-3-benzyl-4-isopropyl-2-oxooxazolidine-5-car-
boxylate (9). To a solution of compound 7 (60 mg, 0.22 mmol) in
THF (2 mL) was added slowly dropwise 1.0 M LHMDS (0.4 mL,
0.44 mmol) at -78 °C. After being stirred for 30 min, TBP (0.22
g, 0.88 mmol) in THF (0.4 mL) was added slowly dropwise to the
reaction mixture over 5 min at -78 °C. The reaction mixture was
maintained at -78 °C for 4 h and then quenched with satd aqueous
NaHCO3 (2 mL). The reaction mixture was extracted with EtOAc
(3 × 5 mL). The combined organic layers were washed with brine
and dried over Na2SO4. The solvent was evaporated, and the residue
was chromatographed on silica gel (hexane/EtOAc ) 2:1) to give
compound 9 (51 mg, 85%) as an oil. [R]20D -37.5 (c 0.5, CHCl3).
Mp 208-209 °C; [R]20 -11.3 (c 0.5, MeOH). IR (KBr): 2954,
D
1
1755, 1600 cm-1. H NMR (300 MHz, D2O): δ 0.97 (6H, m),
1.77 (1H, m), 3.45 (1H, t, J ) 6.5 Hz), 4.07 (1H, d, J ) 4.8 Hz).
13C NMR (75 MHz, D2O): δ 15.5, 17.8, 28.4, 49.8, 71.3, 174.6.
HRMS calcd for C6H13NO3, 147.0895; found, 147.0892.
1
IR (KBr): 3252, 2954, 1755 cm-1. H NMR (300 MHz, CDCl3):
δ 0.89∼0.94 (6H, m), 2.08 (1H, m), 3.49 (1H, t, J ) 3.5 Hz), 3.76
(3H, s), 4.07 (1H, d, J ) 15.3 Hz), 4.60 (1H, d, J ) 3.6 Hz), 4.98
(1H, d, J ) 15.2 Hz), 7.25∼7.45 (5H, m). 13C NMR (75 MHz;
CDCl3): δ 14.7, 17.5, 28.0, 46.2, 52.8, 62.3, 71.1, 127.9, 128.1,
128.8, 135.9, 157.0, 170.0. HRMS calcd for C15H19NO4, 277.1314;
found, 277.1315.
Acknowledgment. This work was supported by the Korea
Science and Engineering Foundation (KOSEF) through the
Regional Animal Industry Research Center at Jinju National
University, Jinju, Korea. We are also grateful for the financial
support of the Brain Korea 21 Program.
Representative Example of the Preparation of Mosher’s
Ester. Preparation of (R)-(+)-R-Methoxy-R-trifluoromethyl-R-
phenylacetic Acid Ester (12). DCC (78 mg, 0.38 mmol) was added
to a solution of (R)-(+)-MTPA in acetonitrile (1.5 mL), which
immediately resulted in the formation of a white precipitate of N,N-
Supporting Information Available: General procedures, prod-
uct characterization data, and NMR spectra. This material is
JO060309M
J. Org. Chem, Vol. 71, No. 13, 2006 5011