3954
T. M. V. D. Pinho e Melo et al. / Tetrahedron 60 (2004) 3949–3955
as an yellow oil (21%). dH 1.92 (3H, s), 3.35–3.50 (3H, m),
4.54–4.61 (1H, m), 7.45–7.51 (2H, m, Ar-H), 7.57–7.63
(1H, m, Ar-H), 7.76–7.79 (1H, m, Ar-H); m/z 205 (Mþ,
100%), 190 (21), 158 (68) and 146 (66). [a]2D5¼269
(c¼0.15, CH2Cl2).
the solvent was purified by column chromatography [ethyl
acetate–hexane (1:1)] giving compound 10 as a white solid
(87.5%). Mp 127.4–129.1 8C (from ethyl acetate–hexane).
dH 3.44 (1H, dd, J¼0.94, 12.7 Hz), 3.63 (1H, dd, J¼7.5,
12.7 Hz), 3.74 (3H, s), 4.88 (1H, dd, J¼1.1, 7.5 Hz), 6.05
(1H, s), 7.12–7.22 (3H, m, Ar-H), 7.31–7.44 (1H, m,
Ar-H); dC 34.0, 53.0, 62.1, 63.0, 116.5, 119.2, 125.1, 125.7,
130.2, 148.2, 149.0, 169.0; m/z 265 (Mþ, 5%), 206 (17) and
179 (100). Anal. Calcd for C12H11NO4S: C, 54.33; H, 4.18;
N, 5.28. Found: C, 53.98; H, 4.43; N, 5.14%. [a]2D5¼þ98
(c¼0.1, CH2Cl2).
4.4.3. Methyl 2-(2-hydroxyphenyl)thiazolidine-4-car-
boxylate 8. L-Cysteine methyl ester hydrochloride (3.45 g,
20 mmol) was dissolved in water (15 mL) and potassium
hydrogen carbonate (2.0 g, 20 mmol) was added following
the addition of a solution of the salicylaldehyde (2.68 g,
22 mmol) in ethanol (15 mL). The reaction mixture was
stirred at room temperature for 30 min. The reaction
mixture was diluted with water and extracted with
dichloromethane. The organic phase was dried and the
solvent was evaporated off giving the methyl 2-(2-hydroxy-
phenyl)thiazolidine-4-carboxylate 8 (60%). Mp 66.7–
4.4.6. (3R,10bR)-5-Oxo-2,3-dihydro-10bH-[1,3]thia-
zolo[3,2-c][1,3]benzoxazine-3-carboxylic acid 11. The
methyl (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo-
[3,2-c][1,3]benzoxazine-3-carboxylate
10
(0.235 g,
1 mmol) and LiI (4 mmol) were dissolved in ethyl acetate
(1.3 mL). The reaction mixture was protected from light and
heated at reflux for 6 h. Water was added (5 mL) and the
solution was acidified with HCl 1 M and extracted with
ethyl acetate. The organic phase was washed with water and
with saturated aqueous solution of NaCl. The organic
solvent was evaporated off. To the residue a saturated
aqueous solution of NaHCO3 was added and the solution
was washed with DCM. The aqueous solution was acidified
with concentrated HCl and extracted with ethyl acetate. The
residue obtained upon removal of the solvent was purified
by column chromatography [ethyl acetate–hexane (1:1)]
giving compound 11 light yellow solid (71%). Mp 173.2–
175.3 8C (from ethyl ether–hexane). dH (CDCl3/DMSO-d6)
3.46–3.51 (1H, m), 3.64 (1H, dd, J¼7.7, 12.7 Hz), 4.81
(1H, dd, J¼1.2, 7.6 Hz), 6.07 (1H, s), 7.09–7.21 (3H, m,
ArH), 7.33–7.38 (1H, m, ArH); dC (CDCl3/DMSO-d6) 36.6,
64.6, 65.6, 119.0, 122.0, 127.5, 128.4, 132.6, 148.5, 151.7,
172.7; m/z [compound 11 treated with CH2N2] 264
[(Mþ2H), 5%], 206 (14) and 179 (100). Anal. Calcd for
C11H9NO4S: C, 52.58; H, 3.61; N, 5.57; S, 12.76. Found: C,
52.41; H, 3.38; N, 5.58; S, 12.83%. [a]2D5¼þ231 (c¼0.1,
MeOH).
68.0 8C (from ethyl ether). n (KBr) 3277 and 1736 cm21
;
dH (two diastereoisomers, ratio 73:27) 3.20–3.25 (1H, m),
3.40–3.47 (1H, m), 3.78 and 3.83 (3H, 2xs), 4.07–4.19 (1H,
m), 5.62 and 5.92 (1H, 2xd, J¼5.7, 4.3 Hz respectively),
6.79–6.94 (2H, m, Ar-H), 7.16–7.26 (2H, m, Ar-H); m/z
239 (Mþ, 19%), 224 (10), 193 (21), 180 (36), 163 (71), 146
(13) and 132 (100). Anal. Calcd for C11H13NO3S: C, 55.21;
H, 5.48; N, 5.85; S, 13.40. Found: C, 55.42; H, 5.72; N,
5.81; S, 13.02%.
4.4.4. Methyl (2R,4R)-N-chlorocarbonyl-2-(2-hydroxy-
phenyl)thiazolidine-4-carboxylate 9. The methyl 2-(2-
hydroxyphenyl)thiazolidine-4-carboxylate
8
(3.75 g,
15.7 mmol) was dissolved in dichloromethane (20 mL)
and potassium hydrogen carbonate (1.57 g, 15.7 mmol) and
a solution of the phosgene in toluene (10 mL, 18.84 mmol)
was added dropwise. The reaction mixture was stirred at
room temperature for 6 h. The reaction mixture was diluted
with water and extracted with ethyl acetate. The organic
phase was dried and the solvent was evaporated off giving
the
methyl
(2R,4R)-N-chlorocarbonyl-2-(2-hydroxy-
phenyl)thiazolidine-4-carboxylate 9 as a white solid
(67%). Mp 145.2–146.9 8C. n (KBr) 3285, 1746 and
1698 cm21. dH (two rotamers) (CDCl3/DMSO-d6) 3.22–
3.41 (2H, m), 3.86 and 3.89 (3H, 2xs), 4.83 and 5.07 (1H,
dd, J¼6.4, 9.4 Hz and approx. t, J¼6.4 Hz, respectively),
6.49 and 6.56 (1H, 2xs), 6.83–6.90 (2H, m, Ar-H), 7.10–
7.18 (1H, m, Ar-H), 7.79–7.86 (1H, m, Ar-H); dC (two
rotamers): major: (CDCl3/DMSO-d6) 31.7, 52.7, 63.8, 66.1,
115.0, 119.1, 125.6, 126.4, 128.7, 147.7, 153.3, 168.8;
minor: 32.4, 52.9, 64.2, 66.8, 115.3, 119.2, 124.2, 126.0,
128.9, 147.7, 153.7, 169.5. m/z 265 [(Mþ2HCl), 4%], 264
(6), 206 (15) and 179 (100). Anal. Calcd for C12H12NO4SCl:
C, 47.77; H, 4.01; N, 4.64; S, 10.62. Found: C, 47.89; H,
4.23; N, 4.57; S, 10.93%. [a]2D5¼þ197 (c¼0.1, CH3-
COCH3).
4.4.7. 5-Acetyl-2-phenyl-2,3-dihydrothiazole 14. A sol-
ution of (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1,3]thia-
zolo[3,2-c][1,3]benzoxazine-3-carboxylic acid 11 (0.75 g,
3 mmol) in Ac2O (5 mL) was heated, in a sealed tube, at
150 8C for 2 h. The reaction was cooled to room temperature
and was diluted with dichloromethane (50 mL). The organic
phase was washed with saturated aqueous solution of
NaHCO3 and with water, dried (MgSO4) and evaporated off.
The crude product was purified by flash chromatography
[ethyl acetate–hexane (1:3)] giving compound 14 as a white
solid (4%). Mp 73.5–74.5 8C (from dichloromethane–
hexane). n (KBr) 1745, 1690 and 1639 cm21. dH 2.40
(1H, s), 4.70 (1H, s), 4.75 (1H, m, NH), 6.73 (1H, s), 7.10–
7.22 (3H, m, Ar-H), 7.32–7.39 (2H, m, Ar-H); dC 30.6, 56.9,
97.4, 116.3, 120.7, 125.3, 125.4, 130.2, 130.3, 148.5, 194.3;
m/z (CI–CH4) 206 [(MHþ), 28%], 137 (5) and 75 (100).
4.4.5. Methyl (3R,10bR)-5-oxo-2,3-dihydro-10bH-
[1,3]thiazolo[3,2-c][1,3]benzoxazine-3-carboxylate 10.
The
methyl
(2R,4R)-N-chlorocarbonyl-2-(2-hydroxy-
phenyl)thiazolidine-4-carboxylate 9 (0.84 g, 2.8 mmol)
was dissolved in ethyl acetate (15 mL). DBU (2 mmol)
was added and the reaction mixture was heated at 50 8C for
2 h. Water was added (15 mL) and the solution was
extracted with ethyl acetate. The organic phase was washed
with water and dried. The residue obtained upon removal of
4.5. X-ray structure determination of methyl (3R,9bS)-5-
oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-
carboxylate 1a
Crystal data. C12H11NO3S, M¼249.28, tetragonal, space
˚
group P41212 (#92), a¼b¼9.424(8), c¼26.209(12) A,