K. Taniguchi et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006) 1089
trated solution, 6 M aqueous NaOH (0.55 mL) was added. The
basic aqueous solution was extracted with i-PrOH (10 mL ꢄ 3),
and the alcoholic solution was washed with 10% aqueous NaCl
(10 mL), then evaporated under reduced pressure. Toluene (4 mL)
ꢇ
was added to the residue, and the solution was stirred at 60 C for
aqueous NaOH (20 mL), and the oily organic layer was extracted
with ether (20 mL ꢄ 3). The combined extract was washed with
brine (20 mL), dried with anhyd. Na2SO4, and concentrated under
reduced pressure to give (R)-310 (8.0 mg, 0.066 mmol, 90.5%,
99.9% ee).
3
0 min. The hot solution was filtered and the filtrate concentrated
under reduced pressure to give (R)-6 (160.8 mg, 0.869 mmol,
6.0%). Optically pure (S)-6 was prepared from diastereomerical-
ly pure (S)-6/(S)-4 by the same procedure.
R)- and (S)-2.18 Diastereomerically pure (R)-2/(S)-1 (202.53
Crystal Structure Analysis of (R)-6/(S)-4 and (S)-6/(S)-4.
Single crystals of (R)-6/(S)-4 and (S)-6/(S)-4 were prepared by
slow evaporation of the solvent from EtOH and an i-PrOH/H2O
(9:1) solution, respectively.
8
ꢇ
(
X-ray intensities were measured up to 2ꢃmax ¼ 55:0 using
˚
mg, 0.557 mmol) was dissolved in 6 M aqueous NaOH (10 mL),
and then extracted with three portions of 10 mL ether. The organic
layer was washed with brine (5 mL), and dried with anhyd.
Na2SO4. The ether solution was concentrated under reduced pres-
sure to give (R)-2 (110.7 mg, 0.524 mmol, 94.1%). Optically pure
graphite-monochromated Mo Kꢀ radiation (ꢄ ¼ 0:71069 A). The
crystal structure was solved by a direct method with SIR9720
and refined by full-matrix least-squares using SHELX97.21
(R)-6/(S)-4ÁEtOH: C27H42N4O6S; formula weight 550.71;
˚
orthorhombic; P212121 (#19); a ¼ 5:9245ð8Þ A, b ¼ 15:104ð2Þ
˚
˚
˚ 3
ꢅ1
(
S)-2 was prepared from diastereomerically pure (S)-2/(S)-1 by
the same procedure.
R)-6/(S)-4. In MeOH (10 mL), (R)-6 (160.8 mg, 0.869
A, c ¼ 34:762ð5Þ A, V ¼ 3110:7ð7Þ A (296 K), Z ¼ 4, Dcalcd ¼
ꢅ3
1:176 g cm , ꢅ(Mo Kꢀ) = 0.147 mm , R ¼ 0:0582 and Rw ¼
0:142 for 7150 observed reflections with I > 2ꢆ from 3035 unique
reflections. Crystallographic data have been deposited with
Cambridge Crystallographic Data Centre: Deposition number
CCDC-285984.
(
mmol), and (S)-4 (277.7 mg, 0.869 mmol) were dissolved, and
the solvent was removed under reduced pressure to afford the salt.
ꢇ
25
D
(
R)-6/(S)-4: mp 102–105 C; ½ꢀꢁ 19.5 (MeOH, c 0.1); IR (KBr)
ꢅ1
1
cm : 3351, 3270, 1679, 1667, 1579, 1391, 1366, 1155; H NMR
400 MHz, CD3OD): ꢂ 7.59 (d, J ¼ 8:0 Hz, 2H), 7.25 (d, J ¼ 8:0
Hz, 2H), 7.17–7.14 (m, 5H), 3.79 (dd, J ¼ 5:2, 6.8 Hz, 1H), 3.49
(S)-6/(S)-4Ái-PrOH: C28H44N4O6S; formula weight 564.73;
˚
(
orthorhombic; P212121 (#19); a ¼ 5:6723ð18Þ A, b ¼ 14:453ð2Þ
˚
˚
˚ 3
A, c ¼ 36:534ð12Þ A, V ¼ 2995:1ð16Þ A (123 K), Z ¼ 4, Dcalcd ¼
ꢅ3
ꢅ1
(
2
dd, J ¼ 3:2, 9.6 Hz, 1H), 3.23 (dd, J ¼ 3:2, 12.8 Hz, 1H), 3.10–
1:252 g cm , ꢅ(Mo Kꢀ) = 0.154 mm , R ¼ 0:0687 and Rw ¼
0:1713 for 6793 observed reflections with I > 2ꢆ from 5813
unique reflections. Crystallographic data have been deposited with
Cambridge Crystallographic Data Centre: Deposition number
CCDC-285983. Copies of the data can be obtained free of charge
the Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge, CB2 1EZ, UK; Fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk).
.99 (m, 3H), 2.96–2.89 (m, 4H), 2.38 (s, 3H), 1.34 (s, 9H).
Optical Purity Determination. The optical purity of ꢀ-meth-
ylbenzylamine (3) was determined on its acetylated derivative by
chiral HPLC analysis. To a stirred solution of 3 (8.0 mg,
0
.066 mmol) in dry THF was added Et3N (6.68 mg, 0.066 mmol)
in dry THF at rt under a nitrogen atmosphere. Acetic anhydride
6.74 mg, 0.066 mmol) in dry THF was added dropwise to the
(
mixture, which was stirred for 30 min at the same temperature.
The reaction mixture solvent was removed under reduced pres-
sure. The residue was dissolved in EtOAc and washed with sat.
aqueous NaHCO3 and brine, and then dried with anhyd. Na2SO4.
After concentration under reduced pressure, the residue was puri-
fied by preparative silica gel TLC (EtOAc) to give (8.8 mg, 0.054
mmol, 81.6%) as a white solid.
The authors, KT and TH, are grateful to Professor Bruce
W. Baldwin of Spring Arbor University for help with English
editing and valuable discussions.
Supporting Information
Chiral HPLC analysis was performed using CHIRALCEL
AD-H (ꢁ 4.6 mm ꢄ 250 mm, detection: UV at 254 nm, flow rate:
Solvent dependences of molar rotation of (S)-(4), i-PrNH2/(S)-
, (R)- and (S)-5, (R)-5/CH3CO2H, (S)-5/CH3CO2H, (R)- and (S)-
, (R)-6/CH3CO2H, (S)-6/CH3CO2H. Optical resolution data of 3
with (R)-1 by changing solvent polarity. These materials are avail-
4
6
ꢅ1
0
.5 mL min , eluent: 10% i-PrOH in hexane).
Optical Rotation Measurement. The solution (10 mL) of a
salt, an acid, or an amine was prepared at a concentration of
0
.1 g/100 mL (c 0.1) with a solvent incubated in a thermostated
ꢇ
bath at 25:0 ꢃ 0:2 C for 1 h. The optical rotation was measured
ꢇ
19
References
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A solvent mixture was prepared by mixing two kinds of solvents
ꢇ
1
a) Optical resolution by means of crystallization. H.
in a certain weight ratio at 25.0 C. The " value of the mixed sol-
Nohira, K. Sakai, In Enantiomer Separation: Fundamentals and
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ðwt %ðsolvent 1Þ ꢄ "ðsolvent 1ÞÞ þ ðwt %ðsolvent 2Þ ꢄ "ðsolvent 2ÞÞ, where
ꢇ
8
"
ðsolventÞ is the dielectric constant at 20 C of a pure solvent.
Optical Resolution of 3 with (R)-1. A solution of (RS)-3
121.18 g, 1 mmol) and (R)-1 (152.15 g, 1 mmol) in water (1.5 mL)
(
2
a) S. Inagaki, H. Shitara, T. Hirose, H. Nohira, Enantiomer
ꢇ
was warmed to 100 C to give a clear solution. The solution was
cooled to room temperature and the resulting crystals were sepa-
rated. The crystals were removed by filtration and washed with
water to afford (R)-3/(R)-1 salt (83.23 mg, 0.30 mmol, 60.9%).
The enantiomer of 3 was obtained by decomposing the separat-
ed diastereomeric salt by the following process: the diastereomer-
ic salt (R)-3/(R)-1 (20.0 mg, 0.073 mmol) was dissolved in 3 M
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Hirose, H. Nohira, Bull. Chem. Soc. Jpn. 2000, 73, 259.
3
a) T. Hirose, K. Naito, M. Nakahara, H. Shitara, Y. Aoki,
H. Nohira, B. W. Baldwin, J. Inclusion Phenom. Macrocyclic
Chem. 2002, 43, 87. b) G. Zhang, Y. Liao, Z. Wang, H. Nohira,
T. Hirose, Tetrahedron: Asymmetry 2003, 14, 3297. c) Z. Wang,