Resolution and Purification of Amino Alcohol Derivatives
J . Org. Chem., Vol. 66, No. 11, 2001 3833
2
5
) +14.38 (c 0.92, MeOH) [lit.8 for
g (50%); 23.9% ee; [R]
D
65.76, 61.80, 59.60, 44.25, 34.30, 29.98, 23.31, 22.14, 19.50.
HPLC analysis of this compound on chiralcel OD column using
hexane/2-propanol (98:2) as eluent revealed that the diaste-
reomer obtained was >99% de. The filtrate fraction after
workup gave the amino alcohol (2R,5S)-(+)-7: yield 1.33 g
2
5
8
2
6% ee, [R]
D
) +15.7 (c 3, MeOH)]; bp 100 °C/1 mmHg [lit
13
bp 70-72 °C/0.2 mmHg]; C NMR (200 MHz, CDCl
8.52, 49.72, 33.26, 26.73, 25.62, 24.85, 24.11, 22.13.
The racemic amino ether 4 was also resolved following the
3
) δ 71.00,
6
2
5
1
same procedure using (R)-(+)-1,1′-bi-2-naphthol (Table 3).
(38%); 10% de; [R]
MHz, CDCl ) δ 0.80-0.85 (m, 3H), 0.98-1.04 (m, 3H), 1.8-
2.5 (m, 6H), 2.7-2.85 (q, 1H), 2.83-3.7 (m, 4H), 4.04 (t, J )
D
) +8.2 (c 1.11, CHCl
3
); H NMR (200
After workup, (1S,2S)-(+)-4 was obtained from the precipitate
3
2
5
fraction: yield 3.9 g (25%); >92% ee [[R]
D
) +33.2 (c 0.97,
2
2
13
CH
2
Cl
2
)] (Table 3, entry 7). The filtrate was concentrated,
7.3 Hz, 1H), 7.27-7.36 (m, 5H); C NMR (200 MHz, CDCl ) δ
3
and the residue was digested in a mixture of ether (100 mL)
145.4, 144.07, 128.66, 128.17, 127.74, 127.37, 126.79, 66.13,
64.70, 64.45, 62.05, 59.83, 48.82, 44.51, 35.81, 34.56, 28.67,
27.26, 23.77, 23.59, 22.47, 21.29, 20.30, 19.80.
and dilute HCl (1 N, 100 mL). After workup, the (1R,2R)-(-
2
5
)
(
-4 was obtained: yield 9.45 g (60%); 59% ee [[R]
D
) +21.24
2
2
-1
c 1.02, CH
2
Cl
2
)]; bp 120 °C/2 mmHg; IR (neat), νmax (cm
)
X-r a y Cr ysta l Str u ctu r e An a lysis. The X-ray structure
data and ORTEP diagrams are given in the Supporting
Information. Final atomic coordinates of the complexes 10b-d
along with lists of the anisotropic thermal parameters hydro-
gen coordinates, bond lengths and bond angles have been
deposited with the Cambridge Crystallographic Data Centre.
They can be obtained, on request, from the Director, Crystal-
lographic Data Centre 12 Union Road, Cambridge CB2 1EZ,
U.K.
1
2
1
2
928, 2854, 1452, 1190, 1103; H NMR (200 MHz, CDCl
3
) δ
.05-1.3 (m, 6H), 1.35-2.20 (m, 8H), 2.25-2.40 (m, 1H), 2.45-
.75 (m, 4H), 3.0-3.15 (m, 1H), 3.35 (s, 3H); 13C NMR (200
MHz, CDCl ) δ 79.97, 68.57, 56.53, 50.44, 31.27, 26.82, 25.84,
3
2
5
5.28, 25.13, 24.53; MS m/z 197, 182, 168, 124, 110, 98, 84,
5, 41.
In a same way, the racemic 5 was also resolved using (R)-
+)-1,1′-bi-2-naphthol (Table 4). After workup, (1S,2S)-(+)-5
was obtained from the precipitate fraction: yield 3.43 g (24%);
(
2
5
6c
5
3% ee; [R]
D
) +51.73 (c 1.052, CH
2 2
Cl ) [lit. for 98% ee,
2
5
Con clu sion s
[R]
D
) -98.0 (c 0.5, CH Cl )] (Table 4, entry 2). It was further
2
2
enriched to obtain sample of 84% ee following the same
procedure. The filtrate fraction after workup gave the amino
Simple and convenient procedures for the resolutions
of racemic amino alcohol derivatives 1-6 to obtain
enantiomerically enriched compounds using chiral 1,1′-
2
5
alcohol (1R,2R)-(-)-5: yield 9.31 g (65%); 16% ee; [R]
D
)
6
c
6d
-
15.61 (c 0.87, CH
2
Cl
2
); mp 79-81 °C (lit. mp 78-81 °C);
) δ 147.91, 129.36, 118.34, 114.40,
1
3
C NMR (200 MHz, CDCl
4.54, 60.16, 33.23, 31.65, 25.04, 24.32
3
bi-2-naphthol and B(OH) have been developed. Purifica-
3
7
tion of the diastereomeric mixture 7 was also developed
The same procedure was also followed for the resolution of
using the same method. The intermediate ammonium
borate complexes were characterized by X-ray diffraction
method. Besides being useful for the synthesis of these
chiral amino alcohol derivatives, the method described
here should also stimulate further work on the resolution
of other related racemic amino alcohols, amines and
polyols via such diastereomeric borate complexes.
(
()-DPP 6 using (R)-(+)-1,1′-bi-2-naphthol (Table 5). After
workup, (R)-(+)-DPP 6 was obtained from the precipitate
2
5
fraction: yield 0.22 g (18%); 90% ee; [R]
D
) +62.1 (c 3, CHCl
) +69.0 (c 3, CHCl )] (Table 5, entry
). It was further enriched following the same procedure to
3
)
2
4
25
[
1
lit. for 100% ee, [R]
D
3
obtain a sample of >99% ee (Table 5, entry 3). The filtrate
fraction after workup gave the amino alcohol (S)-(-)-DPP 6:
2
5
24 13
yield 1 g (80%); 20% ee; [R]
200 MHz, CDCl
26.38, 125.92, 125.58, 77.1, 64.55, 46.78, 26.33, 25.52.
D
) -13.8 (c 3, CHCl
3
);
C NMR
(
3
) δ 148.19, 145.48, 128.24, 127.97, 126.47,
Ack n ow led gm en t. We are thankful to the CSIR
and UGC, New Delhi, for support under a Special
Assistance Program. X-ray structure analysis was car-
ried out using the National Single Crystal X-ray Facil-
ity, School of Chemistry, University of Hyderabad,
funded by DST, New Delhi.
1
In a same way, the diastereomeric mixture (+)-N-[2-(1-
hydroxy-2(S)-isopropyl)ethyl]-5-phenyl-2-pyrrolidine 7 was pu-
rified using (R)-(+)-1,1′-bi-2-naphthol (Table 6). After workup,
(
2R,5S)-(+)-7 was obtained from the precipitate fraction: yield
2
5
1
.47 g (42%); >99% de; [R]
D
3
) +81.89 (C 0.81, CHCl ); IR
-1
1
(
(
(
neat), νmax (cm ) 3443, 3061, 3028, 2960, 2873, 1602; H NMR
200 MHz, CDCl ) δ 0.82-0.85 (d, J ) 6.7 Hz, 3H), 0.9-1.0
d, J ) 6.78 Hz, 3H), 1.80-2.5 (m, 6H), 2.7-2.85 (q, 1H), 3.0-
.5 (m, 4H), 4.04 (t, J ) 7.3 Hz, 1H), 7.26-7.32 (m, 5H); 13
) δ 143.94, 128.31, 127.40, 127.00,
3
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
amino alcohol derivatives 1-7 and X-ray crystal structure
analysis and ORTEP diagrams for the complexes 10b-d . This
material is available free of charge via the Internet at
http://pubs.acs.org.
3
C
NMR (200 MHz, CDCl
3
(
24) Aldrich Catalog Handbook of Fine Chemicals; Aldrich: Mil-
waukee, 1998-1999; catalog no. 38, 233-7.
J O0057755