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T. Shimada et al. / Tetrahedron: Asymmetry 16 (2005) 3807–3813
lene (8.19 g, 34.5 mmol) in THF (20 mL) under an Ar
atmosphere, and the mixture was stirred at rt for
30 min. To the mixture, cooled down to 0 ꢁC, was added
a solution of diethyl oxalate (15.32 g, 104.8 mmol) in
THF (40 mL) at ꢀ78 ꢁC drop by drop over a period
of 1 h. The mixture was stirred at ꢀ78 ꢁC for 2 h and
then at 0 ꢁC for 2 h. Saturated NH4Cl aq (50 mL) was
added to the solution, and the aqueous layer extracted
with ethyl acetate (3 · 100 mL). The combined organic
layers were washed with satd NaCl aq (50 mL), dried
over anhydrous MgSO4, filtered, and concentrated
under reduced pressure to give crude ethyl 6-methoxy-2-
naphthylglycoxylate 2 as a yellow oil. The precipitation
of the oil with hexane/AcOEt (20/1, 630 mL) and the
successive silica gel chromatography (eluent, hexane/
AcOEt = 10/1–9/1) of the residue, recovered upon con-
centrating the filtrate, afforded 2 (8.77 g, 34.0 mmol,
98%) as a white solid. An aliquot was distilled by using
a kugelrohr for the following analyses (3 mmHg; oven
temperature, 120 ꢁC). IR (KBr) cmꢀ1: 3070–2840,
1725, 1680, 1619, 1198, 1175, 1154, 1127, 1095, 1022,
923, 910, 854, 836. 1H NMR (300 MHz, CDCl3) d
1.46 (t, J = 7 Hz, 3H), 3.97 (s, 3H), 4.49 (q, J = 7 Hz,
2H), 7.18 (s, 1H), 7.23 (d, J = 9 Hz, 1H), 7.81 (d,
J = 9 Hz, 1H), 7.78 (d, J = 9 Hz, 1H), 8.03 (d,
J = 9 Hz, 1H), 8.48 (s, 1H). 13C NMR (75 MHz, CDCl3)
d 14.11, 55.45, 62.25, 105.91, 120.05, 124.80, 127.55,
127.58, 127.79, 131.59, 133.23, 138.27, 160.61, 164.13,
186.01. Anal. Calcd for C15H14O4: C, 69.76; H, 5.46.
Found: C, 69.82; H, 5.55.
158.14, 173.97. Anal. Calcd for C15H16O4: C, 69.22; H,
6.20. Found: C, 69.31; H, 6.43.
4.3. (R)-Enriched 6-methoxy-2-naphthylglycolic acid,
(R)-enriched 6-MNGA
A solution of crude 3 (19.40 g, 74.5 mmol) in a mixture
of 12 M KOH aq (10 mL) and 2-propanol (250 mL) was
stirred at 50 ꢁC for 10 min. The solution was concen-
trated under reduced pressure, in order to remove 2-pro-
panol, acidified with 3 M HCl aq (200 mL), and
extracted with 2-butanone (3 · 400 mL). The combined
organic layers were dried over anhydrous Na2SO4, fil-
tered, and concentrated under reduced pressure to give
(R)-enriched 6-MNGA (16.91 g, 72.8 mmol, 98%) as a
pale yellow solid. The ee of (R)-enriched 6-MNGA was
determined by a HPLC analysis (Daicel Chiralcel OJ-
RH; eluent, HClO4 aq (pH 2):CH3CN = 8:2; flow rate,
0.5 mL/min; t1 [(S)-isomer] = 45.1 min, t2 [(R)-iso-
mer] = 39.3 min; the enantiomeric excess, 39%).
4.4. Enantiopure (R)-6-methoxy-2-naphthylglycolic acid,
(R)-6-MNGA
To
a solution of (R)-enriched 6-MNGA (1.69 g,
7.3 mmol, 39% ee) in a mixture of H2O (3 mL) and
EtOH (7 mL) was added (R)-1-phenylethylamine
(PEA) (0.88 g, 7.3 mmol), and the mixture stirred under
reflux for 6 h. After being cooled to rt, the mixture was
left standing overnight, and the deposited colorless crys-
tals were collected by filtration. The salt thus obtained
was recrystallized twice with a mixture of H2O/EtOH
(3/7; 8 and then 5 mL) to afford the diastereopure (R)-
6-MNGAÆ(R)-PEA salt (1.26 g, 3.6 mmol, 49% based
on the amount of (R)-enriched 6-MNGA used) as white
crystals. To the diastereomeric salt was added 1 M HCl
aq (100 mL), and the mixture was stirred for 1 h and
extracted with 2-butanone (3 · 100 mL). The combined
extracts were dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure to afford enan-
tiopure (R)-6-MNGA [0.83 g, 3.6 mmol, quant.; 71%
recovery from (R)-6-MNGA contained in (R)-enriched
6-MNGA used] as a white solid. The ee of (R)-6-MNGA
4.2. (R)-Enriched ethyl 6-methoxy-2-naphthylglycolate, 3
To a suspension of NaBH4 (11.38 g, 300.9 mmol) in
THF (60 mL) was added L-tartaric acid (45.09 g,
300.4 mmol) at rt, and the mixture refluxed for 4 h. It
was then cooled down to rt, after which a solution of
2 (19.50 g, 75.5 mmol) in THF (160 mL) at ꢀ78 ꢁC
was added, and the mixture stirred for 1 h at ꢀ78 ꢁC.
To the mixture was added 1 M HCl aq (100 mL) at
ꢀ78 ꢁC, and the resultant mixture stirred for 15 min at
rt. After removal of THF under reduced pressure, the
aqueous layer was extracted with ethyl acetate
(3 · 100 mL). The combined organic layers were washed
with NaCl aq (100 mL), dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure to give
crude ethyl 6-methoxy-2-naphthylglycolate 3 (19.29 g,
74.1 mmol, 98%) as a white solid. The ee of 3 was deter-
mined by a HPLC analysis (Daicel Chiralcel OJ; eluent,
hexane/2-propanol = 9/1; flow rate, 1.0 mL/min; t1 [(S)-
isomer] = 56.2 min, t2 [(R)-isomer] = 42.1 min; the
enantiomeric excess, 74%). An aliquot (100 mg) was
recrystallized from hexane/AcOEt (8/1, 4 mL/0.5 mL)
for the following analyses. Mp 88.5–90.5 ꢁC; IR (KBr)
cmꢀ1: 3421, 3050–2900, 1737, 1631, 1607, 1487, 1453,
1271, 1064, 1031, 861, 824. 1H NMR (300 MHz, CDCl3)
d 1.22 (t, J = 7 Hz, 3H), 3.52 (d, J = 6 Hz, 1H), 3.92
(s, 3H), 4.17 (dq, J = 7 Hz, J0 = 11 Hz, 1H), 4.28
(dq, J = 7 Hz, J0 = 11 Hz, 1H), 5.29 (d, J = 6 Hz, 1H),
7.14–7.18 (m, 2H), 7.47 (d, J = 8 Hz, 1H), 7.74
(d, J = 8 Hz, 2H), 7.82 (s, 1H). 13C NMR (75 MHz,
CDCl3) d 14.20, 55.47, 62.44, 73.14, 105.77, 119.31,
124.82, 125.89, 127.39, 128.77, 129.74, 133.65, 134.63,
was determined by a HPLC analysis. Mp 173.5–
25
174.0 ꢁC; ½aꢁD ¼ ꢀ144 (c 1.018, MeOH). IR (KBr)
cmꢀ1: 3361, 3276, 3080–2840, 1721, 1689, 1633, 1605,
1
1392, 1227, 1166, 1040, 852, 815. H NMR (300 MHz,
DMSO-d6) d 3.87 (s, 3H), 5.14 (s, 1H), 7.14–7.18 (m,
1H), 7.30 (s, 1H), 7.49–7.51 (m, 1H), 7.77–7.84 (m,
3H). 13C NMR (75 MHz, DMSO-d6) d 55.19, 72.48,
105.80, 118.77, 125.31, 125.59, 126.62, 128.07, 129.37,
133.84, 135.40, 157.34, 174.20. Anal. Calcd for
C13H12O4: C, 67.23; H, 5.21. Found: C, 67.09; H, 5.39.
4.5. Enantiopure (S)-6-methoxy-2-naphthylglycolic acid,
(S)-6-MNGA
After concentration of the mother liquor of the enantio-
separation described above under reduced pressure, 1 M
HCl aq (50 mL) was added to the residue, and the aque-
ous layer extracted with 2-butanone (3 · 50 mL). The
combined organic layers were dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pres-