1340
F. Li et al. / Tetrahedron: Asymmetry 22 (2011) 1337–1341
4.2.4. (R)-3-Benzyl-4-[(S)-hydroxy(4-methylsulfonylphenyl)
methyl]oxazolidin-2-one 8
with brine (3 ꢁ 30 mL), dried over Na2SO4, and concentrated in va-
cuo. The residue was purified by flash column chromatography on
silica gel (AcOEt) to afford 11 as a white powder, yield: 398 mg
To a solution of 6 (500 mg, 2.2 mmol) in anhydrous DMF (2 mL)
was added benzyl isocyanate (350 mg, 2.6 mmol) at rt. After stir-
ring for 10 h at this temperature, 60% NaH (22 mg, 0.44 mmol)
was added portionwise. When the addition was completed, the
reaction mixture was stirred at rt for 1 h. To the reaction mixture
were added CH2Cl2 (20 mL) and H2O (20 mL). The organic layer
was separated, and the aqueous layer was extracted with CH2Cl2
(3 ꢁ 20 mL). The combined organic phase was washed with brine
(3 ꢁ 60 mL), dried over Na2SO4, and evaporated in vacuo. The
residue was purified by chromatography on a silica gel column
(AcOEt/PE = 2:1) to afford 8 as a white powder, yield: 710 mg
(96%); mp 112–113 °C;
½
a 2D0
ꢃ
¼ ꢂ46:6 (c 1.0, ethanol) {lit.1m
½
a 2D0
ꢃ
¼ ꢂ47:1 (c 1.5, ethanol)}; IR (KBr):
m = 3464, 3278, 2936,
2361, 1640, 1402, 1305, 1153, 1064, 771 cmꢂ1 1H NMR (CDCl3):
;
d: 2.75–2.78 (m, 1H, NCH), 3.06 (s, 3H, CH3), 3.41 (dd, 1H,
J = 3.6,9.2 Hz, OCH2), 3.65 (d, 1H, J = 13.2 Hz, CH2Ph), 3.74
(dd, 2H, J = 3.6,9.2 Hz, OCH2), 3.79 (d, 1H, J = 13.2 Hz, CH2Ph),
4.74 (d, 1H, J = 6.8 Hz, OCH), 7.24–7.35 (m, 5H, ArH), 7.58 (d, 2H,
J = 8 Hz, ArH), 7.89 (d, 2H, J = 8 Hz, ArH); MS (ESI): m/z = 336
(M+H)+. Anal. Calcd for C17H21NO4S: C, 60.86; H, 6.30; N, 4.10.
Found: C, 60.84; H, 6.31; N, 4.11.
(90%); mp 143–144 °C; ½a D20
ꢃ
¼ ꢂ1:1 (c 1.0, CHCl3); IR (KBr):
m
= 3415, 1716, 1437, 1321, 1243, 1147, 1096, 960, 770,
4.2.7. (1R,2R)-2-Amino-1-[4-(methylsulfonyl)phenyl]-1,3-
propanediol 12
707 cmꢂ1
;
1H NMR (DMSO-d6): d: 3.18 (s, 3H, CH3), 3.82–3.86
(m, 1H, OCH2), 3.97–4.02 (m, 1H, OCH2), 4.09 (dd, 1H,
J = 4.8,8.4 Hz, NCH), 4.27–4.31 (d, 1H, J = 15.6 Hz, CH2Ph), 4.66–
4.70 (d, 1H, J = 15.6 Hz, CH2Ph), 5.11–5.13 (m, 1H, OCH), 6.11 (d,
1H, J = 4.8 Hz, CHOH), 7.29–7.40 (m, 5H, ArH), 7.53 (d, 2H,
J = 8 Hz, ArH), 7.86 (d, 2H, J = 8 Hz, ArH); 13C NMR (DMSO-d6): d:
44.44, 46.72, 60.04, 61.95, 68.88, 126.74, 127.75, 128.18, 128.53,
129.28, 135.62, 140.18, 145.11, 159.12; MS (ESI): m/z = 362
(M+H)+. Anal. Calcd for C18H19NO5S: C, 59.83; H, 5.29; N, 3.79.
Found: C, 59.86; H, 5.30; N, 3.80.
To a stirred solution of 4.4% formic acid–MeOH (50 mL) were
added 11 (1.37 g, 4.1 mmol) and 10% Pd/C (500 mg) at rt. under
nitrogen atmosphere. After stirring for 10 h, Pd/C was filtered
and the solvent was removed under reduced pressure. The residue
was purified by chromatography on a silica gel column (CH2Cl2/
MeOH = 2:1) to afford 12 as a white solid, yield: 944 mg (94%);
mp 141.7–142 °C; ½a D25
ꢃ
¼ ꢂ20:1 (c 1.0, ethanol) {lit.7 mp 141–
142 °C; ½a 2D5
ꢃ
¼ ꢂ19:8 (c 1.0, ethanol)}; IR(KBr):
m = 3369, 2923,
1642, 1590, 1408, 1300, 1150, 1046, 838, 769 cmꢂ1 1H NMR
;
(DMSO-d6): d: 2.68 (dd, 1H, J = 6,10.8 Hz, CH2), 3.14 (dd, 1H,
J = 6,10.8 Hz, CH2), 3.17 (s, 3H, CH3), 4.61 (d, 1H, J = 4.4 Hz, OCH),
5.43 (br, 1H, OH), 7.56 (d, 2H, J = 8 Hz, ArH), 7.84 (d, 2H, J = 8 Hz,
ArH); MS (ESI): m/z = 246 (M+H)+. Anal. Calcd for C10H15NO4S: C,
48.90; H, 6.18; N, 5.64. Found: C, 48.87; H, 6.19; N, 5.65.
4.2.5. (R)-((R)-3-Benzyl-2-oxooxazolidin-4-yl)[4-(methyl
sulfonyl)phenyl]methyl acetate 10
To a stirred solution of 8 (820 mg, 2.28 mmol) and Et3N
(690 mg, 6.84 mmol) in anhydrous CH2Cl2 (25 mL) was added
dropwise MsCl (520 mg, 4.56 mmol) at 0 °C. After the addition
was complete, stirring was continued for 2 h at rt, and quenched
with 2 M aq HCl (25 mL). The organic phase was separated and
washed with brine (3 ꢁ 25 mL), dried over Na2SO4, and concen-
trated in vacuo to give 9, which was used directly without further
purification.
4.2.8. (4R,5R)-2-(Dichloromethyl)-5-[4-(methylsulfonyl)
phenyl]oxazole-4-methanol 13
To a stirred solution of dichloroacetonitrile (500 mg, 4.6 mmol)
in i-PrOH (5 mL) were added 12 (1.0 g, 4.1 mmol) and concd. HCl
(0.1 mL). The mixture was stirred for 2 h at 70 °C and then agitated
for 14 h at 50 °C. After evaporating the solvent, the residue was
purified by flash column chromatography on silica gel (AcOEt/
PE = 1:2) to afford 13 as a white powder, yield: 1.2 g (87%); mp
Next, a solution of DBU (700 mg, 4.56 mmol) and glacial AcOH
(550 mg, 9.11 mmol) in anhydrous toluene (5 mL) was stirred for
1.5 h at rt, after which 9 was added and the reaction mixture
was heated to 90 °C for 8 h. The resulting mixture was cooled to
rt, diluted with CH2Cl2 (40 mL) and washed with aq HCl (2 M,
30 mL), aq K2CO3 (10% W/V, 30 mL), and brine (30 mL) succes-
sively. The organic phase was dried over Na2SO4, and concentrated
in vacuo. The residue was purified by flash chromatography
(AcOEt/PE = 1:1) to afford 10 as a white solid, yield: 850 mg
144.1–144.5 °C; ½a D20
ꢃ
¼ þ10:9 (c 1.0, ethanol) {lit.1l mp 144–
145 °C; ½a 2D0
ꢃ
¼ þ11:1 (c 5.13, ethanol)}; IR (KBr):
m = 3365, 3005,
2922, 1666, 1299, 1271, 1217, 1150, 1085, 985, 763 cmꢂ1 1H
;
NMR (DMSO-d6): d: 3.21 (s, 3H, CH3), 3.53–3.74 (m, 2H, CH2),
4.04 (m, 1H, NCH), 5.14 (t, 1H, J = 5.6 Hz, OH), 5.72 (d, 1H,
J = 6.4 Hz, OCH), 7.24 (s, 1H, Cl2CH), 7.58 (d, 2H, J = 8 Hz, ArH),
7.97 (d, 2H, J = 8 Hz, ArH); MS (ESI): m/z = 338 (M+H)+. Anal. Calcd
for C12H13Cl2NO4S: C, 42.63; H, 3.89; N, 4.08. Found: C, 42.65; H,
3.88; N, 4.09.
(92%); mp 185–186 °C; ½a D20
ꢃ
¼ ꢂ3:5 (c 1.0, CHCl3); dr >20:1 (1H
NMR does not show the erythro isomer’s signals); IR (KBr):
m
= 3474, 1748, 1648, 1492, 1376, 1299, 1220, 1144, 1088, 949,
769, 675 cmꢂ1 1H NMR (CDCl3): d: 2.08 (s, 3H, CH3), 3.05 (s, 3H,
;
SO2CH3), 4.00–4.06 (m, 2H, OCH2), 4.07–4.11 (m, 1H, NCH), 4.20
(d, 1H, J = 14.4 Hz, CH2Ph), 4.86 (d, 1H, J = 15.2 Hz, CH2Ph), 5.89
(d, 1H, J = 4.8 Hz, OCH), 7.21–7.22 (d, 2H, J = 6.8 Hz, ArH), 7.30–
7.39 (m, 3H, ArH), 7.44 (d, 2H, J = 8.4 Hz, ArH), 7.93 (d, 2H,
J = 8.4 Hz, ArH); 13C NMR (CDCl3): d: 20.85, 44.43, 48.05, 57.14,
63.68, 127.81, 128.07, 128.22, 129.04, 135.70, 141.29, 141.35,
158.32, 169.27; MS (ESI): m/z = 404 (M+H)+. Anal. Calcd for
4.2.9. Florfenicol 1
To a stirred solution of 13 (4.3 g, 12.8 mmol), Et3N (3.9 g,
38.4 mmol), and Et3Nꢀ3HF (3.1 g, 19.2 mmol) in anhydrous THF
(50 mL) was added dropwise PBSF (5.8 g, 19.2 mmol) at rt. After
the addition was complete, the mixture was stirred for 12 h at this
temperature. The solvent was removed, and then CH2Cl2 (50 mL)
and H2O (50 mL) were added. The organic layer was separated
and the aqueous layer was extracted with CH2Cl2 (3 ꢁ 50 mL).
The combined organic layer was then washed with brine
(3 ꢁ 50 mL), dried over Na2SO4 and evaporated under reduced
pressure. The residue was dissolved in i-PrOH (26 mL) and H2O
(14 mL), and then refluxed for 3 h after the mixture was treated
with NaOAc to pH 5. When the hydrolysis was complete, the
temperature was cooled to rt. After removal of the solvent under
vacuum, the residue was purified by flash column chromatogra-
phy on silica gel (AcOEt/PE = 1:1) to afford 1 as a white solid,
C20H21NO6S: C, 59.57; H, 5.25; N, 3.40. Found: C, 59.55; H, 5.26;
N, 3.41.
4.2.6. (2R,3R)-2-Benzylamino-3-(4-methylsulfonylphenyl)-
propane-1,3-diol 11
To a stirred solution of 10 (500 mg, 1.24 mmol) in MeOH
(10 mL) was added 4 M aq KOH (10 mL), and the mixture was re-
fluxed for 1 h under argon atmosphere. After being cooled to room
temperature, MeOH was evaporated and the residue was extracted
with CH2Cl2 (3 ꢁ 10 mL). The combined organic phase was washed
yield: 4.15 g (91%); mp 150–151.5 °C; ½a D20
¼ ꢂ18:1 (c 1.0, DMF)
ꢃ