SYNTHESIS
Ethyl [(4R,5S)-2-Oxo-4,5-diphenyloxazolidin-3-yl]acetate (7):
Papers
1164
1H NMR spectra were recorded in CDCl3 solutions on a JEOL JNM-
EX 270 at 270 MHz or a JEOL JNM-PMX60SI at 60 MHz, and chem-
ical shifts are reported in ppm downfield from TMS. IR spectra were
recorded on a Jasco IR 810 using KBr disks. Mps were determined on
a Mitamura Riken Kogyo MEL-TEMP in open capillary tubes and are
uncorrected. Elemental analyses were performed by a Perkin Eleme-
ter PE 2400. Optical rotations were recorded on a Jasco DIP-360.
CH2Cl2 was distilled over P2O5 and then over CaH2, and stored over
molecular sieves. Merck Kieselgel 60 was used for column chroma-
tography. Wako Wakogel B-5F was used for TLC (0.75 mm) on a
glass plate (20 × 20 cm).
NaH (0.66 g, 60% mineral oil dispersion, 20.8 mmol) was placed in a
two necked flask under argon and washed with anhyd hexane (3 ×
5 mL). After addition of DMF (10 mL) to NaH, a solution of 6
(4.96 g, 20.7 mmol) in DMF (30 mL) was added to the suspension, and
the mixture was stirred for 2 h at r.t.. Then, ethyl bromoacetate
(2.74 mL, 24.9 mmol) was added dropwise in a period of 30 min, and
the mixture was stirred for 30 min. The reaction was quenched with
water (10 mL), and water (100 mL) was added to the mixture. Then, the
solution was extracted with CH2Cl2 (3 × 50 mL). The combined ex-
tracts were washed with sat. aq NaCl (50 mL) and dried (MgSO4). After
removal of the solvent under vacuum, the product was isolated by silica
gel column chromatography (hexane/EtOAc 4:1) to give 6.10 g (89%)
of 7 as a white solid; mp 88°C; [α]D –104.2 (c = 1.00, CHCl3).
1H NMR (CDCl3): δ = 1.3 (t, J = 8 Hz, 3H, CH3CH2), 3.5 (d, J = 18
Hz, 1H, NCH2COO), 4.2 (q, J = 8 Hz, 2H, CH3CH2), 4.6 (d, J = 18
Hz, 1H, NCH2COO), 5.0 (d, J = 9 Hz, 1H, PhCHN), 6.0 (d, J = 9 Hz,
1H, PhCHO), 6.8–7.3 (m, 10H, arom).
Imines; General Procedure:
To a stirred solution of an aldehyde (20 mmol) in anhyd CH2Cl2
(30 mL) at 0°C were successively added an amine (20 mmol) and a
large excess of MgSO4. The resulting mixture was stirred for 10 h at r.t..
The filtered solution was evaporated to give the crude imine, which was
recrystallized from anhyd hexane/CH2Cl2 to give the pure imine.
IR (KBr): ν = 1763, 1738, 1417, 1215, 1022, 708 cm–1.
Anal. Calcd for C19H19NO4: C, 70.14; H, 5.89; N, 4.30. Found: C,
70.05; H, 5.97; N, 4.28.
(4R,5S)-4,5-Diphenyloxazolidin-2-one (6):
A
mixture of (+)-(1S,2R)-2-amino-1,2-diphenylethanol [(+)-1]3
[(4R,5S)-2-Oxo-4,5-diphenyloxazolidin-3-yl]acetic Acid (8):
A THF (20 mL) solution of 7 was added to a solution of KOH (2.99 g,
53.3 mmol) in aq MeOH/THF (35 mL, H2O/MeOH/THF, 3:3:8), and
the mixture was stirred for 1 h at r.t.. Then, 1 M aq HCl (100 mL) was
added to the mixture. The organic layer was extracted with Et2O (3 ×
100 mL), and the combined extracts were washed with sat. aq NaCl (50
mL) and dried (MgSO4). After removal of the solvent under vacuum,
the residue was recrystallized from toluene (45 mL) to give 4.56 g
(87%) of 8 as a white solid; mp 168°C; [α]D –123.3 (c = 1.01, CHCl3).
1H NMR (CDCl3): δ = 3.6 (d, J = 18 Hz, 1H, NCH2COO), 4.6 (d, J =
18 Hz, 1H, NCH2COO), 5.5 (d, J = 8 Hz, 1H, PhCHN), 6.0 (d, J =
8 Hz, 1H, PhCHO), 7.1–7.4 (m, 10H, arom), 10.6 (s, 1H, CO2H).
IR (KBr): ν = 1750, 1704, 1441, 1223 cm–1.
(4.28 g, 20.0 mmol), K2CO3 (0.28 g, 2.03 mmol), and diethyl carbon-
ate (20 mL, 166 mmol) was heated under reflux for 8 h. The resulting
mixture was washed with water (10 mL) and extracted with CH2Cl2
(300 mL), and then the extract was dried (MgSO4). After removal of
the volatiles under vacuum, the residue was recrystallized from tolu-
ene (45 mL) to give 3.93 g (81%) of 6 as a white solid; mp 237–239°C
(lit.18 mp 232.5–233.5°C).
1H NMR (CDCl3): δ = 5.3 (d, J = 8 Hz, 1H, PhCHN), 5.8 (br s, 1H,
NH), 6.1 (d, J = 8 Hz, 1H, PhCHO), 6.9–7.5 (m, 10H, arom).
IR (KBr): ν = 3275, 1745, 1709, 1238, 717 cm–1.
Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C,
75.30; H, 5.47; N, 5.88.
Table 4. Yields, Properties, and Spectroscopic Data of β-Lactams 5
Prod- Yield
mp (°C)
114–115
202–203
177–178
184–186
181–182
IR (KBr)
1H NMR (CDCl3/TMS)
δ, J (Hz)
ucta
(%)
ν (cm–1)
5a
87
1750, 1502, 1238,
760, 703
3.9 (d, J = 14, 1H, NCH2Ph), 4.8 (d, J = 4, 1H, PhCH), 4.9 (d, J = 14, 1H, NCH2Ph),
5.4 (d, J = 4, 1H, PhOCH), 6.6–7.5 (m, 15H, arom)
5b
5c
5d
5e
88
1750, 1518, 1498,
1245
3.8 (s, 3H, OMe), 5.4 (d, J = 5, 1H, PhCH), 5.6 (d, J = 5, 1H, PhOCH), 6.7–7.8 (m,
14H, arom)
85
1742, 1518, 1242
3.8 (s, 6H, 2OMe), 5.4 (d, J = 5, 1H, p-MeOC6H4CH), 5.6 (d, J = 5, 1H, PhOCH), 6.6–
7.6 (m, 13H, arom)
95
1742, 1518, 1498,
1235
3.8 (s, 3H, OMe), 5.4 (d, J = 5, 1H, p-ClC6H4CH), 5.6 (d, J = 5, 1H, PhOCH), 6.8–7.6
(m, 13H, arom)
quant.
1738, 1518, 1252,
1120, 755
3.8 (s, 3H, OMe), 5.0 (dd, J = 5, 8, 1H, PhCH=CHCH), 5.5 (d, J = 5, 1H, PhOCH), 6.4
(dd, J = 8, 16, 1H, PhCH=CHCH), 6.9 (d, J = 16, 1H, PhCH=CHCH), 6.9–7.8 (m,
14H, arom)
5fb
5g
5h
92
89
89
147–148
185–196
192–195
1745, 1515, 1240,
758
3.8 (s, 3H, OMe), 5.2 (d, J = 5, 1H, PhC≡CCH), 5.5 (d, J = 5, 1H, PhOCH), 6.8–8.1
(m, 14H, arom)
1782, 1765, 1725,
1395, 728, 705
4.2 (d, J = 16, 1H, NCH2Ph), 5.0 (d, J = 5, 1H, PhthNCH), 5.1 (d, J = 16, 1H,
NCH2Ph), 5.5 (d, J = 5, 1H, PhOCH), 7.1–8.1 (m, 14H, arom)
1750, 1723, 1515,
1388, 1250, 835
3.8 (s, 3H, OMe), 5.1 (dd, J = 5, 8, 1H, PhCH=CHCH), 5.7 (d, J = 5, 1H, PhthN), 6.3
(dd, J = 8, 16 Hz, 1H, PhCH=CHCH), 6.6–8.1 (m, 14H, arom + PhCH=CHCH)
a All new compounds gave satisfactory microanalyses: C ± 0.31, H ± 0.30, N ± 0.30.
b Data for the cis-isomer.