163.87 (s), 166.05 (s), and 188.54 (s). Anal. Calcd for
C13H13NO4SCl2: C, 44.6; H, 3.7; N, 4.0; S, 9.2. Found: C,
45.2; H, 3.8; N, 4.0; S, 9.4.
sion was formed, which was stirred for 18 h at rt. Then
600 mL of 4 N HCl solution was added in portions. After
4 h of stirring, all solids were dissolved and the solution
was extracted twice with toluene (2 and 1 L, respectively).
After evaporation of the toluene layers, 400 g (66%) of 10
was recovered. The aqueous phase was concentrated to a
thick suspension of 500 mL. The solid product was filtered,
washed with acetone, and dried. Yield: 330 g of 12 (63%
yield, 92% on used aldehyde). Threo:erythro: 97:3. Mp:
>250 °C. 1H NMR (D2O) δ 2.47 (s, 3H), 4.19 (d, 1H), 5.10
(d, 1H), and 7.35 (2d, 4H) [erythro isomer 4.31 (d) and 5.20
(d)]. In DMSO-d6 the amide protons are observed at δ 7.43
and 7.96. 13C NMR (DMSO-d6): δ 14.54 (q), 58.20 (d),
71.10 (d), 125.41 (d), 127.36 (d), 136.56 (s), 137.51 (s), and
167.83 (s). IR (cm-1): 1699, 1486, 1039, 813, 540.
HRMS: calcd for C10H15N2O2SCl (M+ - HCl) 226.0776,
found: 226.0780. Anal. Calcd for C10H15N2O2SCl: C, 45.7;
H, 5.8; N, 10.7. Found: C, 45.4; H, 5.8; N, 10.6.
threo-3-[4-(Methylsulfonyl)phenyl]serinamide Hydro-
chloride Salt (13). A solution of 4.4 g (40 mmol) of
glycinamide hydrochloride salt in 5 mL of water was made
alkaline (pH 12.5) with 12 mL of 4 N NaOH solution. To
this solution was added 15 mL of MeOH, followed by 14.75
g (80 mmol) of 11. An additional 20 mL of MeOH was
added to this reaction mixture. The heterogeneous mixture
was stirred for 40 h at rt. The thick suspension was acidified
with 15 mL of 4 N HCl solution and stirred for 1 h. The
remaining solid was filtered, resuspended in 100 mL of water,
stirred again for 1 h, and filtered off (7.5 g of impure 11).
The combined filtrates were washed with CHCl3 and
concentrated to a thick suspension. The solid was filtered,
washed with water and MeOH, and dried. Yield: 8.7 g of
13 (29.5 mmol, 74%). Mp: 223-225 °C dec. Threo:
erythro: >95:5. 1H NMR (D2O): δ 3.27 (s, 3H), 4.26 (d,
1H), 5.31 (d, 1H), 7.75 (d, 2H), and 8.03 (d, 2H), [erythro
signals at 4.39 (d) and 5.48 (d)]. In DMSO-d6 the amide
signals are observed at δ 7.52 and 8.03. 13C NMR (D2O):
δ 43.88 (q), 59.08 (d), 71.52 (d), 128.23 (d), 128.29 (d),
139.68 (s), 145.03 (s), and 169.59 (s). IR (cm-1): 1702,
1282, 1145, 544. HRMS: calcd for C10H15N2O4SCl 241.0647
(M+, -HCl, -H2O), found 241.0666. Anal. Calcd for C10-
H15N2O4SCl: C, 40.7; H, 5.1; N, 9.5. Found: C, 40.3; H,
5.1; N, 8.9.
(2S,3R)-N-(Dichloroacetyl)-3-[4-(methylthio)phenyl]-
serine Methyl Ester (9). A solution of 1.05 g (3.0 mmol)
of 8 and 42 mg (1 mol %) of Ru2Cl4‚[(R)-BINAP]2‚N(C2H5)3
in 20 mL of CH2Cl2 was stirred under 1000 psi of H2 pressure
at 50 °C in an autoclave for 66 h. The reaction mixture
was concentrated in vacuo and purified by chromatography
(eluent, CHCl3/1% MeOH). Yield: 30 mg (85 µmol, 3%)
of 9 as a brownish oil. Rf: 0.22 (CHCl3/1% MeOH). 1H
NMR: see rac-9. Diastereomeric ratio threo:erythro: g95:
5. Eethreo: 85% (by HPLC; column, Chiracel OD; eluent,
hexane/i-PrOH, 90:10; flow, 1.0 mL/min; temperature, 20
°C; detection, UV 210 nm). MS(CI): 334/336 (M+ + 1,
-H2O). A 700 mg amount of starting material 8 was
recovered.
When the reaction was repeated with freshly prepared Ru2-
Cl4‚[(R)-BINAP]2‚N(C2H5)3, 9 was obtained in 67% yield
and eethreo 15%.
4-(Methylsulfonyl)benzaldehyde (11). To a solution of
10 (50 g, 0.33 mol) and HC(OCH3)3 in 700 mL of MeOH
was added p-TsOH (0.5 g, 3 mmol). After 1.5 h of stirring
at rt, KO-t-Bu (0.40 g, 3 mmol) was added. The mixture
was concentrated in vacuo to give the dimethyl acetal in
quantitative yield as a viscous colorless oil. 1H NMR: δ
2.45 (s, 3H), 3.30 (s, 6H), 5.35 (s, 1H), 7.25 (d, 2H), and
7.35 (d, 2H).
To an ice-cooled solution of the acetal (65 g, 0.32 mol)
in 600 mL of CH2Cl2 was added dropwise over 30 min a
solution of m-CPBA in CH2Cl2 (prepared by dissolving 235
g of 50% m-CPBA in 1200 mL of CH2CL2, extraction with
300 mL of water, and drying over Na2SO4) in such a way
that the solvent did not reflux. The reaction mixture was
stirred for 16 h. The mixture was filtered and washed with
CHCl3. The filtrate was washed with 1 N NaOH solution,
0.25 M NaI solution, 1 N NaOH solution, 0.25 M Na2S2O3
solution, and water. After drying (Na2SO4) and concentration
in vacuo, the sulfone acetal (59.8 g, 0.26 mol, 81%) was
obtained as an oil, which crystallized on standing. 1H
NMR: δ 3.10 (s, 3H), 3.35 (s, 6H), 5.52 (s, 1H), 7.65 (d,
2H), and 7.95 (d, 2H).
To a solution of the sulfone acetal (59.7 g, 0.26 mol) in
THF (600 mL) was added 600 mL of a 4% H2SO4 solution
in 45 min. The mixture was stirred for 16 h at rt, 300 mL
of saturated NaHCO3 was added, and the product was filtered
off. Yield of 11: 44.6 g (0.24 mol, 93%) as a white
crystalline solid. Mp: 158-159 °C. 1H NMR: δ 3.21 (s,
3H), 7.99 (d, 2H), 8.18 (d, 2H), and 10.15 (s, 1H). (Overall
yield: 75%.)
threo-3-[4-(Methylthio)phenyl]serinamide Hydrochlo-
ride Salt (12). A solution of 221 g (2 mol) of glycinamide
hydrochloride salt in 1500 mL of water was brought to pH
12.5 with 570 mL of 4 N NaOH solution. To this solution
at 25 °C was added dropwise a solution of 608 g (4 mol) of
10 in 1500 mL of MeOH at such a speed that the temperature
rose to 35-40 °C. To the suspension formed was added an
additional 100 mL of MeOH. After 2-3 h a thick suspen-
The identical compound was made by oxidation of threo-
3-[4-(methylthio)phenyl]serinamide hydrochloride salt (12):
570 mg of 12 was suspended in 10 mL of AcOH. To this
was added 12 mL of peracetic acid (made by mixing 3 parts
of AcOH with 1 part of 30% H2O2). After 2 h reaction time
excess peroxides were decomposed with 10% Pd/C by
stirring for 2 h at 40 °C. The Pd/C was filtered off, and the
solution was concentrated. The residue was washed with
MeOH and dried. Yield: 400 mg (62%) of a white solid,
identical to the material described above.
Lipase-Catalysed Resolution of 7
To a solution of 100 mg of 7 in 3 mL of 50 mM KH2-
PO4/K2HPO4 buffer (pH 7.5) was added 10 mg of lipase (20
µL in the case of alcalase). The mixtures were stirred for 3
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