Synthesis of mexiletine stereoisomers and related compounds via S(N)Ar nucleophilic substitution of a Cr(CO)3-complexed aromatic fluoride

Full text of DOI:10.1021/jo982287c

J . Org. Chem. 1999, 64, 3373-3375
3373
7
Syn th esis of Mexiletin e Ster eoisom er s a n d
Rela ted Com p ou n d s via S Ar Nu cleop h ilic
Su bstitu tion of a Cr (CO) -Com p lexed
fluorobenzenetricarbonylchromium complex, 2, to afford
a corresponding 2,6-dimethylphenyl ether complex as the
sole detectable product. Oxidative decomposition of the
chromium-arene complexes followed by treatment of the
free base products with HCl gave crystalline hydrochlo-
ride salt derivatives of novel mexiletine analogues in 28-
N
3
Ar om a tic F lu or id e
David G. Loughhead,* Lee A. Flippin,* and
Robert J . Weikert
6
6% overall yield. Thus a simple, one-pot synthesis of
each isomer of 1 was planned which would make use of
the aryl chromium tricarbonyl complex 2 and the com-
mercially available enantiomers of 2-amino-1-propanol.
As shown in eq 1, the sodium alkoxide derived from (S)-
Department of Medicinal Chemistry, Neurobiology Unit,
Roche Bioscience, 3401 Hillview Avenue,
Palo Alto, California 94304
(
+)-2-amino-1-propanol was treated with aryl chromium
Received November 18, 1998
tricarbonyl complex 2. Iodine-induced decomposition of
the product chromium complex, followed by chromatog-
As part of a program aimed at discovering new sodium
channel blockers, we required authentic samples of the
enantiomers of the class I-B antiarrhythmic agent mexi-
letine (1). Both enantiomers of mexiletine have previ-
ously been prepared via classical resolution and via
enzymatic hydrolysis of an N-acyl derivative. Recently,
the (R)-isomer of mexiletine was prepared in 7.2% overall
yield using a stereospecific, four-step procedure which
established that this isomer is levorotatory. We report
here a short, unambiguous synthesis of both isomers of
mexiletine. We also report that the procedures used to
prepare the stereoisomers of mexiletine can serve as a
general and efficient route to related aryl aminoalkyl
ethers.
8
raphy, provided (S)-mexiletine, isolated as its hydrochlo-
ride salt. A similar sequence, using (R)-(-)-2-amino-1-
propanol provided (R)-mexiletine hydrochloride. The
enantiomeric purities of these materials were determined
by chiral HPLC analysis to be 99% ee or greater. Specific
rotations observed for the hydrochloride salts were
consistent with previously reported stereochemical as-
signments.
1
2
,3
4
3
(1)
N
The S Ar coupling procedure used to prepare the
mexiletine stereoisomers was used as a general route to
9
several related aryl aminoalkyl ethers; the structures
and yields of these products are presented in Figure 1.
In summary, a novel and practical stereospecific
synthesis of both enantiomers of mexiletine has been
achieved. It has also been demonstrated that the coupling
procedure described herein may serve as an attractive
route to a variety of aryl aminoalkyl ethers.
Chromium tricarbonyl complexes of aryl halides have
long been known to undergo facile nucleophilic aromatic
substitution with simple, monofunctional alkoxides.5
More recently Davies and Hume reported that sodium
salts of (1R,2S)-ephedrine and (1S,2S)-pseudoephedrine
displace fluoride from the chromium tricarbonyl com-
plexes of fluorobenzene or p-fluoroanisole to give aryl
ether chromium tricarbonyl complexes; these intermedi-
ates were employed without isolation in a novel variation
of the Smiles rearrangement to afford complexed aniline
Exp er im en ta l Section
Gen er a l P r oced u r es. Melting points are uncorrected. Amino
alcohols were obtained from Aldrich and were used without
purification. Yields reported are relative to chromium complex
2. NMR spectra were obtained in DMSO-d6 (unless otherwise
6
derivatives. We have found that a variety of primary and
1
13
secondary alkoxides bearing unprotected primary, sec-
ondary, or tertiary amino functionality smoothly displace
fluoride from the sterically congested 1,3-dimethyl-2-
specified) at 300 MHz ( H) and at 75 MHz ( C). Chiral HPLC
analysis of mexiletine stereoisomers was performed using a
Chiralcel OD-H column eluted at a flow rate of 0.8 mL/min with
9
7:3:0.1 hexane/2-propanol/diethylamine.
S)-(+)-Mexiletin e Hyd r och lor id e. To a solution of 226 mg
(
(1) (a) Koppe, H.; Zeile, K.; Kummer, W.; Stahle, H.; Danneberg, P.
(3.01 mmol) of (S)-(+)-2-amino-1-propanol in 7 mL of THF at
U.S. Patent 3,659,019, 1972. (b) Campbell, N. P. S.; Chaturvedi, N.
C.; Kelly, J . G.; Strong, J . E.; Shanks, R. G.; Pantridge, J . F. Lancet
1
973, ii, 404-407. (c) Talbot, R. G.; Clark, R. A.; Nimmo, J .; Neilson,
J . M. M.; J ulian, D. G.; Prescott, L. F. Lancet 1973, ii, 399-404.
2) Turgeon, J .; Uprichard, A. C. G.; Belanger, P. M.; Harron, D.
W. G.; Grech-Belanger, O. J . Pharm. Pharmacol. 1991, 43, 630-635.
3) Franchini, C.; Cellucci, C.; Corbo, F.; Lentini, G.; Scilimati, A.;
(7) Mahaffy, C. A. L.; Hamilton, J . Synth. React. Inorg. Met.-Org.
Chem. 1986, 16, 137-143.
(8) Semmelhack, M. F.; Hall, H. T. J . Am. Chem. Soc. 1974, 96,
7091-7092.
(
(
(9) Compounds 3 and 5 have been previously reported in the
abstracts from the 1st Italian-Swiss Meeting on Medicinal Chemistry;
however, we were unable to discover any reference to the physical
characterization or method of synthesis of these substances. Franchini,
C.; Catalano, A.; Corbo, F.; Duranti, A.; Lentini, G.; Tortorella, V.
Poster A16 (compound 3) and Duranti, A.; Catalano, A.; Franchini,
C.; Lentini, G.; DeLuca, A.; Natuzzi, F. Poster A14 (compound 5), 1st
Italian-Swiss Meeting on Medicinal Chemistry, Turin, Italy, Septem-
ber 23-26, 1997.
Tortorella, V.; Stasi, F. Chirality 1994, 6, 590-595.
(
4) Phillips, G. T.; Shears, J . H. U.K. Patent GB 2246774 A1, 1992.
(
5) (a) Nicholls, B.; Whiting, M. C. J . Chem. Soc. 1959, 551-556.
(
b) Brown, D. A.; Raju, J . R. J . Chem. Soc. A 1966, 40-43. (c) Knipe,
A. C.; McGuinness, S. J .; Watts, W. E. J . Chem. Soc., Chem. Commun.
1
979, 842-843. (d) Mahaffy, C. A. L.; Paulson, P. L. J . Chem. Res.,
Synop. 1979, 128. (e) For a recent example, see: Semmelhack, M. F.;
Hilt, G.; Colley, J . H. Tetrahedron Lett. 1998, 39, 7683-7686.
(6) Davies, S. G.; Hume, W. E. Tetrahedron Lett. 1995, 36, 2673-
(10) Aberg, G. A. K.; Af Ekenstam, B. T. U.S. Patent 4822778 A,
1989.
2
674.
1
0.1021/jo982287c CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/01/1999

3
374 J . Org. Chem., Vol. 64, No. 9, 1999
Notes
F igu r e 1. Yields of isolated hydrochloride salts are presented in parentheses.
room temperature was added 122 mg (3.05 mmol) of a 60%
dispersion of NaH in mineral oil. After 0.5 h, 1,3-dimethyl-2-
fluorobenzenetricarbonylchromium7 (394 mg, 1.52 mmol) was
added and the reaction mixture was allowed to stir at room
temperature overnight. Iodine (1.50 g, 5.9 mmol) was then
cautiously added. After an additional 2 h of stirring, the mixture
separated and the aqueous phase was washed multiple times
with additional ether. The combined ether washes were dried
(MgSO ) and concentrated to give a residue which was dissolved
4
in a small amount of ether and treated with HCl in ethanol.
The precipitated salt of the desired product was isolated by
filtration.
was diluted with EtOAc and washed with 5% aqueous NaHSO
The aqueous phase was made alkaline with aqueous NaOH
before the phases were separated. The aqueous phase was
3
.
(R)-(-)-2-(2,6-Dim eth ylph en oxy)-1-ph en yleth ylam in e h y-
d r och lor id e9 (3): prepared in 34% yield via method A using
1
(R)-(-)-2-phenylglycinol; mp 273.0-273.5 °C (EtOH); H NMR
washed with Et
brine, dried with MgSO
chromatographed using a 150 mL sintered glass funnel filled
with 230-400 mesh SiO and eluting with 2:98, 5:95, and 10:90
MeOH/CH Cl to provide 186 mg (68%) of an oil. A solution of
this material in 15 mL of Et O was made acidic with 1 M HCl
in Et O, and the precipitate was collected and recrystallized from
EtOH/Et O to give 136 mg (41%) of the title compound as a white
solid, mp 202.1-202.7 °C. The enantiomeric purity of this
material was determined to be 99% ee using chiral HPLC, t
2
O, and the combined organics were washed with
δ 2.10 (s, 6H), 4.00-4.12 (m, 2H), 4.73 (br t, J ) 5.4 Hz, 1H),
6.92 (dd, J ) 8.6, 6.0 Hz, 1H), 7.00 (br d, J ) 6.6 Hz, 2H), 7.39-
4
, and concentrated. The residue was
1
3
7.51 (m, 3H), 7.61-7.67 (m, 2H), 8.87 (br s, 3H); C NMR δ
2
17.4, 55.7, 73.5, 126.0, 129.5, 130.3, 130.5, 132.1, 136.8, 155.8;
+
2
2
MS m/z (%) 241 (M , 2), 106 (100); [R]
D
) -4.2° (c 0.55, MeOH).
2
Anal. Calcd for C16
H
20ClNO: C, 69.18; H, 7.26; N, 5.04. Found:
2
C, 68.93; H, 7.23; N, 5.17.
(S)-(+)-2-(2,6-Dim eth ylph en oxy)-1-ph en yleth ylam in e h y-
d r och lor id e (4): prepared in 35% yield via method A using (S)-
2
R
(+)-2-phenylglycinol; mp 270.3-270.9 °C (EtOH/Et O); [R] )
2
D
1
1
3
7
4
5
8.2 min: H NMR δ 1.36 (d, J ) 6.6 Hz, 3H), 2.26 (s, 6H), 3.52-
+3.5° (c 0.48, MeOH). Anal. Calcd for C16
H20ClNO: C, 69.18;
H, 7.26; N, 5.04. Found: C, 69.08; H, 7.33; N, 5.09.
.64 (m, 1H), 3.76-3.86 (m, 2H), 6.94 (dd, J ) 8.6, 6.4 Hz, 1H),
.03 (d, J ) 7.4 Hz, 2H), 8.37 (br s, 3H); 13C NMR δ 16.6, 17.6,
(R)-(-)-1-Ben zyl-2-(2,6-dim eth ylph en oxy)eth yla m in e h y-
d r och lor id e9 (5): prepared in 40% yield via method A using
(R)-(+)-2-amino-3-phenyl-1-propanol; mp 186-187 °C (EtOH/
+
8.4, 73.3, 125.8, 130.4, 132.0, 155.9; MS m/z (%) 179 (M , 10),
3
8 (100); [R]
D
) +2.6° (c 1.00, MeOH, lit. +2.20°). Anal. Calcd
for C11
H
18ClNO: C, 61.25; H, 8.41; N, 6.49. Found: C, 60.99; H,
Et O); H NMR δ 2.16 (s, 6H), 3.01 (dd, J ) 13.8, 9.0 Hz, 1H),
1
2
8
.38; N, 6.49.
3.22 (dd, J ) 13.8, 5.4 Hz, 1H), 3.65-3.93 (m, 3H), 6.92 (dd, J
) 8.5, 6.1 Hz, 1H), 7.00 (br d, J ) 6.9 Hz, 2H), 7.23-7.38 (m,
5H), 8.65 (br s, 3H); 13C NMR δ 15.9, 34.8, 52.2, 69.8, 124.3,
(
R)-(-)-Mexilet in e H yd r och lor id e. The procedure de-
scribed above, applied to (R)-(-)-2-amino-1-propanol, provided
the title compound in 32% yield, mp 202.8-203.6 °C, >99% ee
127.0, 128.6, 128.9, 129.2, 130.4, 136.3, 154.3; MS m/z (%) 255
) - 2.9° (c 1.00, MeOH, lit.3
+
by chiral HPLC (t
2.18°). Anal. Calcd for C11
R
17.1 min); [R]
18ClNO: C, 61.25; H, 8.41; N, 6.49.
D
(M , 2), 164(100); [R]
D
) -20.1° (c 0.40, MeOH). Anal. Calcd for
22ClNO: C, 69.97; H, 7.60; N, 4.80. Found: C, 69.66; H,
7.53; N, 4.77.
-
H
17
C H
Found: C, 61.58; H, 8.49; N, 6.42.
Gen er a l P r oced u r e A. To a THF solution of the amino
alcohol was added 1 equiv of sodium hydride dispersion followed,
(S)-(+)-1-Ben zyl-2-(2,6-d im eth ylp h en oxy)eth yla m in e h y-
d r och lor id e (6): prepared in 28% yield via method A using (S)-
2
0-30 min later, by the addition of 0.5 equiv of chromium
complex 2. After the reaction had stirred at room temperature
for 1-16 h, it was cautiously treated with 2-3 equiv of I
(-)-2-amino-3-phenyl-1-propanol; mp 185-186 °C (EtOH); [R]
) +24.5° (c 0.07, MeOH). Anal. Calcd for C17 22ClNO‚0.1H O:
D
H
2
2
.
C, 69.54; H, 7.62; N, 4.77. Found: C, 69.50; H, 7.66; N, 4.93.
1-(2,6-Dim et h ylp h en oxym et h yl)cyclop en t yla m in e h y-
d r och lor id e (7): prepared in 37% yield via method A using
Workup, as described above for mexiletine, was followed by
chromatography, salt formation, and recrystallization to provide
the desired product.
1
1-amino-1-cyclopentanemethanol; mp 251-253 °C (EtOH); H
Gen er a l P r oced u r e B. A THF solution of the amino alcohol
was treated with 1 equiv of sodium hydride dispersion and then,
NMR δ 1.60-1.75 (m, 2H), 1.76-2.03 (m, 6H), 2.28 (s, 6H), 3.36
(s, 2H), 6.94 (dd, J ) 8.4, 6.3 Hz, 2H), 7.04 (br d, J ) 7.3 Hz,
1H), 8.39 (br s, 3H); 13C NMR δ 16.0, 23.8, 33.4, 63.3, 73.4, 124.3,
1
5 min later, with 0.5-0.7 equiv of chromium complex 2. After
+
the reaction mixture had been refluxed for 1 h, it was cooled to
room temperature and poured into water. The water was
extracted multiple times with ether, and the combined ether
128.9, 130.4, 153.7; MS m/z (%) 219 (M , 1.5), 108(100). Anal.
Calcd for C14H22ClNO: C, 65.74; H, 8.67; N, 5.48. Found: C,
65.80; H, 8.76; N, 5.42.
fractions were treated with solid I
persisted. After 20-60 min, water was added followed by solid
Na until the color was dissipated. After the aqueous layer
had been made alkaline with 6 M NaOH, the phases were
2
until a dark red-brown color
(R)-(-)-2-(2,6-Dim eth ylp h en oxym eth yl)p yr r olid in e h y-
d r och lor id e (8): prepared in 43% yield via method A using (R)-
1
2
S
2
O
3
(-)-2-pyrrolidinemethanol; mp 150.9-151.3 °C (EtOAc);
H
NMR δ 1.69-2.21 (m, 4H), 2.27 (s, 6H), 3.13-3.36 (m, 2H), 3.79-

Notes
J . Org. Chem., Vol. 64, No. 9, 1999 3375
1
3
7
.90 (m, 1H), 3.94 (dd, J ) 10.1, 4.6 Hz, 1H), 4.07 (dd, J ) 10.1,
.5 Hz, 1H), 6.94 (dd, J ) 8.4, 6.4 Hz, 1H), 7.04 (br d, J ) 7.3
(EtOAc) (lit.10 mp 171-173 °C); H NMR δ 1.46-2.16 (m, 6H),
2.28 (s, 6H), 2.97 (br s, 3H), 3.02-3.19 (m, 1H), 3.38-3.51 (m,
2H), 3.86-3.97 (m, 1H), 4.05-4.17 (m, 1H), 6.97 (dd, J ) 8.5,
7.0 Hz, 1H), 7.06 (br d, J ) 7.4 Hz, 2H), 10.28-10.47 (m, 1H);
1
3
Hz, 2H), 9.1-10.2 (m, 2H); C NMR δ 16.1, 22.5, 26.1, 44.5,
5
7
+
8.8, 69.7, 124.1, 128.7, 130.3, 154.5; MS m/z (%) 205 (M , 3),
0 (100); [R] ) -4.3° (c 0.39, MeOH). Anal. Calcd for C13
1
3
D
H
20
-
C NMR δ 16.2, 21.3, 22.4, 26.3, 41.0, 55.3, 63.5, 69.9, 124.3,
128.9, 130.2, 154.5; CI-MS m/z 234 (MH ). Anal. Calcd for
C H24ClNO: C, 66.77; H, 8.97; N, 5.19. Found: C, 66.58; H,
15
+
ClNO: C, 64.59; H, 8.34; N, 5.79. Found: C, 64.81; H, 8.31; N,
.78.
()-2-[2-(2,6-Dim eth ylp h en oxy)eth yl]p ip er id in e h yd r o-
ch lor id e (9): prepared in 48% yield via method A using (()-2-
5
(
8.68; N, 4.92.
(()-3-(2,6-Dim eth ylp h en oxy)-1-m eth ylp ip er id in e h yd r o-
ch lor id e (13): prepared in 67% yield via method B using (()-
3-hydroxy-1-methylpiperidine; mp 157.0-158.5 °C; H NMR δ
1
piperidineethanol; mp 205.7-206.3 °C (CH
.42-1.82 (m, 5H), 1.89-2.03 (m, 2H), 2.17-2.31 (m, 1H), 2.23
s, 6H), 2.80-2.92 (m, 1H), 3.18-3.31 (m, 2H), 3.82-3.89 (m,
3
CN); H NMR δ
1
(
2
9
1
1
1.60-1.80 (m, 1H), 1.85-2.10 (m, 2H), 2.15-2.26 (m, 1H), 2.38
(br s, 6H), 2.90 (br s, 3H), 2.90-3.10 (m, 1H), 3.10-3.28 (m, 1H),
3.40-3.50 (m, 1H), 3.60-3.72 (m, 1H), 4.38-4.52 (m, 1H), 7.09
H), 6.91 (dd, J ) 8.3, 6.5 Hz, 1H), 7.02 (br d, J ) 7.5 Hz, 2H),
13
.19 (br s, 2H); C NMR δ 16.4, 22.1, 28.2, 33.9, 44.1, 53.8, 68.0,
+
24.2, 129.1, 130.7, 155.7; MS m/z (%) 233 (M , 6), 84 (100). Anal.
(dd, J ) 8.3, 6.5 Hz, 1H), 7.19 (br d, J ) 7.5 Hz, 2H), 11.5 (br s,
Calcd for C15
6.91; H, 8.83; N, 5.09.
H24ClNO: C, 66.77; H, 8.97; N, 5.19. Found: C,
1H); 13C NMR δ 18.6, 22.1, 30.3, 44.3, 54.4, 57.3, 75.6, 125.8,
6
130.9, 132.3, 155.4; MS m/z (%) 219 (M , 10), 98 (100), 70 (18).
+
(
S)-(-)-2-(2,6-Dim eth ylp h en oxym eth yl)-1-m eth ylp yr r ol-
Anal. Calcd for C14H22ClNO: C, 65.74; H, 8.67; N, 5.48. Found:
C, 66.01; H, 8.86; N, 5.66.
en d o-3-(2,6-Dim et h ylp h en oxy)-8-m et h yl-8-a za b icyclo-
id in e h yd r och lor id e (10): prepared in 38% yield via method
A using (S)-(-)-1-methyl-2-pyrrolidinemethanol; mp 184.1-
1
1
84.6 °C (EtOAc); H NMR (MeOH-d
4
) δ 2.05-2.28 (m, 3H), 2.32
[
3.2.1]octa n e h yd r och lor id e (14): prepared in 66% yield via
(
3
s, 6H), 2.33-2.49 (m, 1H), 3.14 (s, 3H), 3.21-3.34 (m, 1H), 3.71-
1
method B using endo-3-tropanol; mp >280 °C; H NMR (DMSO-
.90 (m, 2H), 4.13 (br d, J ) 4.4 Hz, 2H), 6.95 (dd, J ) 8.5, 6.3
d
6
/TFA-d
1
) δ 2.24 (s, 6H), 2.15-2.30 (m, 4H), 2.40-2.60 (m, 4H),
1
3
Hz, 1H), 7.04 (br d, J ) 7.6 Hz, 2H); C NMR (MeOH-d
2
2
4
) δ 16.6,
2
(
.69 (s, 3H), 3.77-3.93 (m, 2H), 3.97 (br t, J ) 5 Hz, 1H), 6.86
2.5, 27.2, 40.7, 58.3, 68.9, 69.6, 125.8, 130.2, 131.6; CI-MS m/z
13
br t, J ) 7.4 Hz, 1H), 6.99 (br d, J ) 7.4 Hz, 2H); C NMR δ
+
D
22
20 (MH ); [R] ) -26.9° (c 0.35, MeOH). Anal. Calcd for C14H -
1
8.1, 23.3, 35.3, 38.1, 61.3, 74.0, 123.2, 129.3, 129.6, 156.7; MS
ClNO: C, 65.74; H, 8.67; N, 5.48. Found: C, 65.48; H, 8.56; N,
.37.
+
m/z (%) 245 (M , 12), 124 (100), 96 (12). Anal. Calcd for C16
ClNO: C, 68.19; H, 8.58; N, 4.97. Found: C, 68.22; H, 8.52; N,
.21.
()-3-(2,6-Dim et h ylp h en oxy)-1-a za bicyclo[2.2.2]oct a n e
h yd r och lor id e (15): prepared in 61% yield via method B using
()-3-quinuclidinol; mp 254.5-255.5 °C; 1H NMR (DMSO-d
TFA-d ) δ 1.60-1.92 (m, 3H), 2.22 (s, 6H), 2.25-2.45 (m, 2H),
.95-3.50 (m, 5H), 3.69-3.80 (m, 1H), 4.20-4.27 (m, 1H), 6.93
dd, J ) 8.2, 6.6 Hz, 1H), 7.04 (br d, J ) 7.5 Hz, 2H); C NMR
δ 16.4, 16.8, 20.0, 25.3, 44.6, 45.5, 52.4, 75.5, 123.7, 129.0, 129.9,
55.1; MS m/z (%) 231 (M , 35), 110 (100). Anal. Calcd for C15
ClNO: C, 67.28; H, 8.28; N, 5.23. Found: C, 67.04; H, 8.18; N,
.43.
24
H -
5
(
()-2-[2-(2,6-Dim et h ylp h en oxy)et h yl]-1-m et h ylp yr r oli-
5
d in e h yd r och lor id e (11): prepared in 33% yield via method A
(
1
using (()-1-methyl-2-pyrrolidineethanol; mp 159.8-160.4 °C; H
NMR δ 1.71-2.10 (m, 4H), 2.23 (s, 6H), 2.22-2.48 (m, 2H), 2.83
(
6
/
(
6
br s, 3H), 2.97-3.10 (m, 1H), 3.40-3.60 (m, 2H), 3.81 (br t, J )
1
.6 Hz, 2H), 6.92 (dd, J ) 8.3, 6.5 Hz, 1H), 7.03 (br d, J ) 7.5
2
(
13
Hz, 2H), 10.71 (br s, 1H); C NMR δ 17.0, 22.0, 30.2, 31.5, 39.2,
13
+
5
1
5
5.9, 66.5, 69.4, 124.8, 129.7, 131.3, 156.2; MS m/z (%) 233 (M ,
5), 84 (100). Anal. Calcd for C15 24ClNO: C, 66.77; H, 8.97; N,
.19. Found: C, 66.74; H, 8.91; N, 4.99.
H
+
1
22
H -
(
()-2-(2,6-Dim e t h ylp h e n oxym e t h yl)-1-m e t h ylp ip e r i-
5
10
d in e h yd r och lor id e (12): prepared in 63% yield via method
A using (()-1-methyl-2-piperidinemethanol; mp 173.2-173.7 °C
J O982287C