Efficient synthesis of a new series of piperidine ring-modified analogs of (±)-threo-methyl phenyl(piperidin-2-yl)acetate

Article abstract of DOI:10.1080/00397911.2010.543305

A series of novel piperidine ring modified analogs of (±)-threo- methyl phenyl (piperidin-2-yl)acetate was synthesized by direct alkylation and reductive amination procedure, using sodium borohydride over molecular sieves. The chemical structures of these compounds were established based on mass spectra, ¹H NMR spectra, and CHN elemental analysis data. Several significant modifications in the literature methodologies were made to make the reaction more efficient, and good yields were generally obtained. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.543305

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Efficient Synthesis of a New Series of
Piperidine Ring-Modified Analogs of
(±)-threo-Methyl Phenyl(piperidin-2-
yl)acetate
a
Babatunde Ojo
a
Department of Chemistry, Fort Valley State University, Fort Valley,
Georgia, USA
Accepted author version posted online: 17 Nov 2011.Published
online: 27 Feb 2012.
To cite this article: Babatunde Ojo (2012) Efficient Synthesis of a New Series of Piperidine Ring-
Modified Analogs of (±)-threo-Methyl Phenyl(piperidin-2-yl)acetate, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:12, 1731-1745,
DOI: 10.1080/00397911.2010.543305
To link to this article: http://dx.doi.org/10.1080/00397911.2010.543305
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1
Synthetic Communications , 42: 1731–1745, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.543305
EFFICIENT SYNTHESIS OF A NEW SERIES OF
PIPERIDINE RING-MODIFIED ANALOGS OF (ꢀ)-
THREO-METHYL PHENYL(PIPERIDIN-2-YL)ACETATE
Babatunde Ojo
Department of Chemistry, Fort Valley State University, Fort Valley,
Georgia, USA
GRAPHICAL ABSTRACT
Abstract A series of novel piperidine ring modified analogs of (ꢀ)-threo-methyl phenyl
(
piperidin-2-yl)acetate was synthesized by direct alkylation and reductive amination
procedure, using sodium borohydride over molecular sieves. The chemical structures of these
1
compounds were established based on mass spectra, H NMR spectra, and CHN elemental
analysis data. Several significant modifications in the literature methodologies were made to
make the reaction more efficient, and good yields were generally obtained.
Keywords Methyl phenyl(piperidin-2-yl)acetate; piperidine; reductive amination; ring
modification
INTRODUCTION
Dopamine is an important neurotransmitter in the central nervous system, and
malfunction of dopaminergic systems is implicated, for example, in Parkinson’s dis-
ease, Huntington’s chorea, and schizophrenia. This neurotransmitter is also involved
in the reward system believed to underlie drug addition. Its action is primarily
mediated by several receptor subtypes with different structural requirements for
exogenous ligands. In both animals and humans, cocaine is one of the most reinfor-
cing drugs known; hence it has great abuse potential. The abuse of cocaine (and other
Received November 2, 2010.
Address correspondence to Babatunde Ojo, Department of Chemistry, Fort Valley State
University, 1005 State University Drive, Fort Valley, GA 31030, USA. E-mail: ojob@fvsu.edu
1
731

1732
B. OJO
stimulant drugs) is one of the greatest concerns of the society today and has therefore
become a focus of medical, social, and political leaders. Methyl phenyl(piperidin-2-
[
yl)acetate was first synthesized in 1944 by Panizzon and was identified as a stimulant
1]
[
2]
0
0
in 1954. A review on the synthesis of commercially pure ( R, 2 R)-(þ)-threo-methyl
[
3]
phenyl(piperidin-2-yl)acetate hydrochloride has been published. The original
[1]
method of Pannizzon for the synthesis of methyl phenyl(piperidin-2-yl)acetate often
gave mixtures of products that may require tedious chromatographic separations,
resulting generally in a very poor yield. A diverse group of methylphenidate analogs
have been synthesized. Because both the phenyl ring and the piperidine ring of
methylphenidate are important for the binding at the DAT (dopamine transporter
protein), the design of the analogs of methylphenidate has mainly focused on modify-
ing these two pharmacophores.
Detailed reviews of piperidine analogs of cocaine, tropanes, and GBR 12935
[
4,5]
compounds have been reported in the literature.
piperidine ring-modified analogs of methylphenidate has been reported in the
literature.
Furthermore, the synthesis of
[
5,6]
These analogs basically involve the replacement of the piperidine ring
with other secondary amines with five, seven, and eight-membered rings. Over the
past several years, the chemical synthesis of a series of (ꢀ)-threo-methyl phenyl
[
4–14]
(piperidin-2-yl)acetate analogs has been reported,
but not many reports include
piperidine ring-modified analogs synthesis with methyl phenyl(piperidine-2-yl)
acetate as the starting point for the syntheses.
The rationale for this study is to synthesize a new series of piperidine ring-
modified analogs of (ꢀ)-threo-methyl phenyl(piperidin-2-yl)acetate derivatives by
making several significant modifications to existing literature methodologies to make
the reaction more efficient and hence produce compounds with improved yields. The
compounds should be useful in the synthesis of novel ligands for testing as pharma-
ceutical agents. We now report the efficient synthesis of several new piperidine
ring-modified analogs of methyl phenyl(piperidin-2-yl)acetate.
CHEMISTRY
The synthesis of methyl phenyl(piperidin-2-yl)acetate has previously been
described in the literature, based on the alkylation of 2-bromopyridine with various
[
1]
phenylacetonitrile anions. The original method developed by Panizzon was modi-
[14]
fied in a previous report. This study further expands the scope of these modifica-
tions to synthesize a new series of benzyl, substituted-benzyl, and other aromatic
ring derivatives. The alkylation reagent was carefully selected so that it could serve
two purposes: (1) protection of the amine function and (2) easy modification into
the required pharmacophore. The N-alkylation was accomplished by using three
methods depending upon the final product: (a) using a substituted alkyl halide in
[
7,8]
[8,9]
the presence of a base,
stituted aldehyde followed by reduction with sodium cyanoborohydride (reductive
(b) using a substituted acid chloride,
and (c) using a sub-
[
8]
amination). A summary of these methods is described in Schemes 1 and 2, respect-
ively. Several synthetic strategies employed for the direct alkylation of methyl
phenyl(piperidin-2-yl)acetate to produce analogs with extended methylene linkage
between the piperidine nitrogen and the benzyl ring synthesis, as well as other aro-
matic rings, was unsuccessful because of formation of polyalkylated compounds.

METHYL PHENYL(PIPERYDIN-2-YL)ACETATE ANALOGS
1733
Scheme 1. General scheme for synthesis of N-benzl methyl phenyl(piperidin-2-yl)acetate analogs.
Reagents and conditions: (a) Powdered potassium carbonate (K CO ), acetone; (b) potassium iodide
KI), room temperature, overnight; (c) potassium iodide (KI), acetone; and (d) potassium carbonate
CO ), room temperature, 24 h.
2
3
(
(
K
2
3
Thus, the synthesis of these new piperidine ring-modified analogs was successfully
achieved by a standard reductive amination procedure, using sodium borohydride
over molecular sieves (Scheme 2). The synthesis was extended to other aromatic
systems and their substituted analogs.
Scheme 2. General scheme for synthesis of extended alkyl chain and other aromatic rings methyl phenyl
(piperidin-2-yl)acetate analogs. Reagents and conditions: (a) triethylyamine (Et
molecular sieves (4A); and (b) sodium cyanoborohydride (NaBH CN), room temperature, overnight.
3
N), methanol (MeOH),
3

1734
B. OJO
Table 1. Physical and analytical data of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate derivatives
Elemental analysis
(
%) (Calc.=found)
Comp.
no.
Mp
ꢁ
Yield
(%)
Molecular
formula (M)
n
1
1
R
( C)
C
H
N
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
3
3
A
B
C
D
E
F
Phenyl
69–70
81
78
74
71
65
61
62
55
82
87
89
85
80
68
88
86
87
78
C
21
H
323.20)
25NO
2
78.03
78.01
70.60
70.62
70.60
70.61
70.60
70.63
68.50
68.51
74.76
74.75
78.34
78.33
78.64
78.65
78.90
78.91
79.15
79.17
79.39
79.38
69.31
69.32
69.31
69.32
62.71
62.72
72.84
72.84
72.84
72.84
74.08
74.07
74.08
74.07
7.80
7.81
6.78
6.77
6.78
6.77
6.78
6.77
6.57
6.56
7.72
7.71
8.08
8.08
8.33
8.32
8.56
8.55
8.78
8.77
8.98
8.97
7.05
7.05
7.05
7.05
6.11
6.10
7.41
7.40
7.41
7.40
7.47
7.46
7.47
7.46
4.32
4.31
3.90
3.91
3.90
3.91
3.90
3.91
7.60
7.60
3.95
3.94
4.14
4.13
3.98
3.98
3.83
3.82
3.68
3.68
3.55
3.54
4.25
4.23
4.25
4.26
3.85
3.85
4.46
4.46
4.46
4.45
8.63
8.63
8.63
8.62
(
2-Chlorobenzyl
3-Chlorobenzyl
4-Chlorobenzyl
4-Nitrobenzyl
4-Methoxybenzyl
Phenyl
151–152
179–180
169–170
170–172
164–165
154–155
160–161
140–141
136–137
156–157
180–181
175–176
172–173
170–171
181–182
153–154
159–160
C
21
H
24NO
2
Cl
(
357.16)
1
1
1
1
2
3
4
5
6
1
1
1
1
1
1
1
C
C
21
H
24NO
2
Cl
Cl
(
357.16)
21
H24NO
2
(
357.16)
21 24 2 4
C H N O
(
368.18)
27NO
353.47)
27NO
337.22)
29NO
351.22)
31NO
365.25)
33NO
379.29)
35NO
393.27)
23NO
329.20)
23NO
329.20)
22NO
363.91)
23NO
313.20)
23NO
313.20)
C
22
H
3
(
A
B
C
D
E
A
B
C
D
E
F
C
C
C
C
C
22
H
2
2
2
2
2
(
Phenyl
23
H
(
Phenyl
24
H
(
Phenyl
25
H
(
Phenyl
26
H
(
2-Thiopene
3-Thiopene
5-Chlorothiopene
2-Furan
C
19
H
2
S
(
C
19
H
2
S
(
C
19
H
2
SCl
(
C
C
19
H
3
3
(
3-Furan
19
H
(
2-Pyridyl
C
C
20
H
24
N
2
0
2
(
324.20)
G
3-Pyridyl
20 24 2
H N 0
2
(
324.20)
(
Continued )

METHYL PHENYL(PIPERYDIN-2-YL)ACETATE ANALOGS
1735
Table 1. Continued
Elemental analysis
(
%) (Calc.=found)
Comp.
no.
Mp
ꢁ
Yield
(%)
Molecular
formula (M)
n
1
R
( C)
C
H
N
3
4
H
4-Pyridyl
140–141
Liquid
82
80
C
20
24
H N
0
2 2
74.08
74.07
72.87
72.85
7.47
7.46
8.56
8.55
8.63
8.62
5.67
5.68
(
324.20)
25NO
247.165)
1
H
C
15
H
2
(
Several synthetic strategies were employed for the direct alkylation of methyl
phenyl(piperidine-2-yl)acetate to produce analogs with extended methylene linkage
between the piperidine nitrogen and the benzyl ring synthesis. These methods were
unsuccessful because of formation of polyalkylated compounds. Thus, the synthesis
of these new N-alkylated derivatives was successfully achieved by a standard
reductive amination procedure, using sodium cyanoborohydride over molecular
sieves (Scheme 2).
RESULTS AND DISCUSSION
The results of the alkylation of methyl phenyl(piperidin-2-yl)acetate with
appropriate aryl halide, substituted aryl halide, and aldehyde in suitable solvents to
give the desired methyl phenyl(piperidin-2-yl)acetate derivatives are summarized in
Table 1. From the results, these compounds were synthesized in good yields (80%
and above), and pure crystals of each compound were obtained. Several solvents were
attempted for the alkylation process. In general, acetone, methanol, and methylene
chloride were found to be the best solvents of choice because the products were
obtained in relatively pure form (single spot on thin-layer chromatography, TLC).
Several solvent systems were attempted for the recrystallization process, but a mixture
of ethyl acetate and hexane was found to give the purest form of these compounds,
supported by spectral data. The chemical structure of these compounds was
1
established based on the mass (MS) and H NMR spectral data. All compounds
synthesized in this study gave satisfactory elemental analysis data and were within
0
.4% of calculated values.
CONCLUSION
In conclusion, a mixture of methyl phenyl(piperidin-2-yl)acetate, powdered
potassium carbonate, and appropriate aryl halide and substituted aryl halide was
reacted in an appropriate solvent at room temperature overnight by standard
alkylation procedure. Also, a mixture of methyl phenyl(piperidin-2-yl)acetate, the
appropriate aldehyde in methanol, followed by the addition of triethylamine
(Et N) and sodium cyanoborohydride (NaBH CN), was reacted by a standard
3 3
reductive amination procedure. An aqueous workup procedure gave the desired
target compounds in good yield. This route may serve as an excellent synthetic meth-
odology for synthesis of new piperidine ring-modified analogs of (ꢀ)-threo-methyl
phenyl(piperidin-2-yl)acetate in good yields.

1736
B. OJO
EXPERIMENTAL
Compounds were synthesized utilizing reagents commercially available from
Aldrich Chemical Co. and Fisher Scientific without further purification. Melting
points were determined in open capillary tubes on a Meltemp melting-point apparatus
1
and are uncorrected. H NMR spectra were recorded with a Bruker Avance (AV) 400
spectrometer at 400 MHz. Chemical shifts are quoted in parts per million (ppm) from
internal standard tetramethylsilane (TMS). All solvents and chemicals were of research
grade and were obtained from Merck and Lancaster. The progress of the reaction was
monitored by TLC. Mass spectra were obtained using a Micromass LCT mass spec-
trometer operating at 20 eV. Elemental analyses were performed on a Perkin-Elmer
2
400 CHN analyzer instrument and were within 0.4% of calculated values.
(
ꢀ)-threo-N-Benzyl Methyl Phenyl(piperidin-2-yl)acetate (1A)
A mixture of (ꢀ)-threo-methyl phenyl(piperidin-2-yl)acetate (100mg, 0.40mmol),
powdered potassium carbonate (250mg), and benzyl bromide (70 mg, 0.46mmol) in
acetone (20 mL) was stirred overnight at room temperature. The mixture was filtered,
and the filtrate and the washings were evaporated in vacuo. The residue was chromato-
graphed on 5 g of silica gel using 5% MeOH in chloroform to give pure (TLC, one spot
R ¼ 0.42) compound. The hydrochloride salt was obtained by addition of 1 M HCl in
F
ether to a methanol solution of the residue, evaporation of solvents to dryness in vacuo,
and recrystallization (EtOAc–hexane) provided 112 mg (81%) of 1A as white solid: mp
ꢁ
9–70 C (lit. ; H NMR (CDCl ): d 1.6–1.1 (m, 6H), 3.03–2.95 (m, 1H), 2.58–2.53
3
[15] 1
6
(
(
m,1H), 3.66–3.49 (m,1H), 3.71 (s, 3H, OCH ), 3.97–3.93 (d, 1H, J ¼ 13.4), 3.84–3.97
3
d, 1H, J ¼ 13.2), 4.2–4.1 (d, 1H, J ¼ 10.4), 7.4–7.2 (m, 10H, aromatic-H) ppm; MS-CI
m=z 324.20 calcd. for C H NO (MHþ). Anal. calcd. for C H NO : C, 78.03; H,
2
1
26
2
21 26
2
7
.80; N, 4.32. Found: C, 78.01; H, 7.81; N, 4.31.
(ꢀ)-threo-N-(2-Chlorobenzyl) Methyl Phenyl(piperidin-2-yl)-
acetate (1B)
A mixture of (ꢀ)-threo-methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 2-chlorobenzyl (82 mg, 0.40 mmol) in acetone (20 mL) was alkylated by a method
virtually identical to that employed to synthesize 1A. The compound was converted to
its hydrochloride salt, and recrystallization from EtOAc–hexane provided 100 mg
ꢁ
78%) of 1B as a off-white solid: mp 151–152 C; H NMR (CDCl ): d 1.6–1.1 (m,
3
1
(
6
3
7
H), 3.03–2.95 (m, 1H), 2.58–2.53 (m, 1H), 3.66–3.49 (m, 1H), 3.69 (s, 3H, OCH3),
.96–3.91 (d, 1H, J ¼ 13.3), 3.78–3.74 (d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.2),
.4–7.2 (m, 9H, aromatic-H) ppm; MS-CI m=z 358.160 calcd. for C H NO Cl
2
1
25
2
(
7
MHþ). Anal. calcd. for C H NO Cl: C, 70.60; H, 6.78; N 3.90. Found: C,
2
1
25
2
0.62; H, 6.77; N, 3.91.
(ꢀ)-threo-N-(3-Chlorobenzyl) Methyl Phenyl(piperidin-2-yl)-
acetate (1C)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 3-chlorobenzyl (82 mg, 0.40 mmol) in acetone (20 mL) was alkylated by a method

METHYL PHENYL(PIPERYDIN-2-YL)ACETATE ANALOGS
1737
virtually identical to that employed to synthesize 1A. The compound was converted to
its hydrochloride salt, and recrystallization from EtOAc–hexane provided 70 mg
ꢁ
74%) of 1C as a off-white solid: mp 179–180 C; H NMR (CDCl ): d 1.6–1.1 (m,
3
1
(
6
3
7
H), 3.03–2.95 (m, 1H), 2.58–2.53 (m, 1H), 3.66–3.49 (m, 1H), 3.69 (s, 3H, OCH3),
.96–3.91 (d, 1H, J ¼ 13.3), 3.78–3.74 (d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.2),
.4–7.2 (m, 9H, aromatic-H) ppm; MS-CI m=z 358.160 calcd. for C H NO Cl
2
1
25
2
(
7
MHþ). Anal. calcd.. for C H NO Cl: C, 70.60; H, 6.78; N, 3.90. Found: C,
2
1
25
2
0.60; H, 6.78; N, 3.90.
(ꢀ)-threo-N-(4-Chlorobenzyl) Methyl Phenyl(piperidin-2-yl)-
acetate (1D)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 4-chlorobenzyl (64 mg, 0.40 mmol) in acetone (20 mL) was alkylated by a method
virtually identical to that employed to synthesize 1A, except that KI (0.25 g) was
added to the reaction mixture to enhance the reactivity of the 4-chlorobenzyl chloride.
In addition, the reaction time was increased to 48 h, and the crude product was filtered
through a silica-gel column to give the pure compound. The compound was converted
to its hydrochloride salt, and recrystallization from EtOAc–hexane provided 70 mg
ꢁ
71%) of 1D as a off-white solid: mp 169–170 C; H NMR (CDCl ): d 1.6–1.1 (m,
3
1
(
6
3
7
H), 3.03–2.95 (m, 1H), 2.58–2.53 (m, 1H), 3.66–3.49 (m, 1H), 3.69 (s, 3H, OCH3),
.96–3.91 (d, 1H, J ¼ 13.3), 3.78–3.74 (d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.2),
.4–7.2 (m, 9H, aromatic-H) ppm; MS-CI m=z 358.160 calcd. for C H NO Cl
2
1
25
2
(
7
MHþ). Anal. calcd. for C H NO Cl: C, 70.60; H, 6.78; N, 3.90. Found: C,
2
1
25
2
0.63; H, 6.77; N, 3.91.
(ꢀ)-threo-N-(4-Nitrobenzyl) Methyl Phenyl(piperidin-2-yl)-
acetate (1E)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 4-nitrobenzyl bromide (86 mg, 0.40 mmol) in acetone (20 mL) was alkylated by a
method virtually identical to that employed to synthesize 1A. The resulting compound
was converted to its hydrochloride salt, and recrystallization from EtOAc–hexane
ꢁ
1
provided 70 mg (65%) of 1E as a yellow solid: mp 170–172 C; H NMR (CDCl ): d
3
1
3
1
.6–1.1 (m, 6H), 3.03–2.95 (m, 1H), 2.58–2.53 (m, 1H), 3.66–3.49 (m, 1H), 3.69 (s,
H, OCH ), 3.96–3.91 (d, 1H, J ¼ 13.3), 3.78–3.74 (d, 1H, J ¼ 13.2), 4.18–4.14 (d,
3
H, J ¼ 10.2), 7.4–7.2 (m, 9H, aromatic-H) ppm; MS-CI m=z 369.18 calcd. for
C H N O (MHþ). Anal. calcd. for C H N O : C, 68.50; H, 6.57; N, 7.60. Found:
2
1
24
2
4
21 24
2
4
C, 68.51; H, 6.56; N, 7.60.
(ꢀ)-threo-N-(4-Methoxylbenzyl) Methyl Phenyl(piperidin-2-yl)-
acetate (1F)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 4-methoxylbenzyl chloride (63 mg, 0.40 mmol) in acetone (20 mL) was alkylated
by a method virtually identical to that employed to synthesize 1D. The resulting
compound was converted to its hydrochloride salt, and recrystallization from

1738
B. OJO
ꢁ
1
EtOAc–hexane provided 80 mg (61%) of 1F as a white solid: mp 164–165 C; H
NMR (CDCl ): d 1.6–1.1 (m, 6H), 3.03–2.95 (m, 1H), 2.58–2.53 (m, 1H), 3.66–3.49
3
(
3
7
m, 1H), 3.70 (s, 3H, OCH ), 3.80 (s, 3H, OCH ), 3.96–3.91 (d, 1H, J ¼ 13.3),
3
3
.78–3.74 (d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.2), 7.4–7.2 (m, 5H, aromatic-H),
.6–7.5 (m, 2H, aromatic-H), 8.1–8.0 (m, 2H, aromatic-H) ppm; MS-CI m=z 354.20
calcd. for C H NO (MHþ). Anal. calcd. for C H NO : C, 74.76; H, 7.72; N,
2
2
28
3
22 28
3
3
0
.95. Found: C, 74.75; H, 7.71; N, 3.94.
Synthesis of 4-Phenylbutyraldehyde
In a 100-mL round-bottom flask fitted with a reflux condenser, PCC (2.15 g,
.009985 mol) was suspended in dry methylene chloride (30 mL). A solution of 4-phe-
nylbutanol (1 g, 0.006656 mol) in methylene chloride (10 mL) was then added in one
portion to the magnetically stirred suspension to give a dark reaction mixture. The
reaction mixture was allowed to proceed at room temperature overnight. Dry ether
(60 mL) was added, and the supernatant liquid was decanted from a black gum.
The insoluble residue was washed with dry ether (3 ꢂ 20 mL) and becomes a black
granular solid. The combined organic solution was passed through a short pad of
florisil and the solvent removed in vacuo provided 75 mg (76%) of titled compound
1
as a yellow liquid. H NMR (CDCl ): consistent with the structure of the compound
with characteristic aldehyde proton.
3
Synthesis of 5-Phenylpentyraldehyde
In a 100-mL round-bottom flask fitted with a reflux condenser, PCC (1.968 g,
.00913 moles) was suspended in dry methylene chloride (30 mL). A solution of
-phenylpentanol (1 g, 0.006656 mol) in methylene chloride (10 mL) was oxidized
0
5
by a method similar to that described for 4-phenylbutyraldehyde. Removal of solvent
1
in vacuo provided 65 mg (71%) of the titled compound as a yellow liquid. H NMR
(CDCl ): consistent with the structure of the compound with characteristic aldehyde
proton.
3
Synthesis of 6-Phenylhexyraldehyde
In a 100-mL round-bottom flask fitted with a reflux condenser, PCC (1.81 g,
.008413 mol) was suspended in dry methylene chloride (30 mL). A solution of 6-phe-
nylhexanol (1 g, 0.006656 mol) in methylene chloride (10 mL) was oxidized by a
0
method similar to that described for 4-phenylbutyraldehyde. Removal of solvent in
1
vacuo provided 65 mg (71%) of the titled compound as a yellow liquid. H NMR (CDCl ):
consistent with the structure of the compound with characteristic aldehyde proton.
3
(
ꢀ)-threo-N-(Phenylethyl) Methyl Phenyl(piperidin-2-yl)acetate (2A)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
(0.172 g) and 2-phenylacetaldehyde (0.2 mL) was dissolved in methanol (25 mL), fol-
lowed by the addition of Et N (0.4 g), and reductively alkylated. Into the solution
were added 4-A molecular sieves (4 g), and the reaction mixture was stirred at room
3

METHYL PHENYL(PIPERYDIN-2-YL)ACETATE ANALOGS
1739
temperature for 1.5 h. NaBH CN (0.15 g, 2.38 mmol) was added into the solution,
3
and the reaction was continued for an additional 18 h. The mixture was filtered,
and the filtrate and the washings were evaporated in vacuo. The residue was chroma-
tographed on 10 g of silica gel using CHCl –MeOH (25:1) to give pure (TLC, one spot
3
R ¼ 0.38) titled compound. The hydrochloride salt was obtained by addition of 1 M
F
HCl in ether to a methanol solution of the residue, evaporation of solvents to dryness
in vacuo, and recrystallization (EtOAc–hexane) provided 87mg (62%) of 2A as a white
ꢁ
1
solid: mp 154–155 C; H NMR (CDCl ): d 1.6–0.9 (m, 6H), 2.4 (m, 1H), 2.8–2.6 (t, 2H),
3
2
.9–3.0 (t, 2H), 3.4 (m, 1H), 3.65 (s, 3H, OCH ), 4.2–4.1 (d, 1H, J ¼ 10.4), 7.4–7.2
22 28 2
3
(m, 10H, aromatic-H) ppm; MS-CI m=z 338.22, calcd. for C H NO (MHþ). Anal.
calcd. for C H NO : C, 78.34; H, 8.08; N, 4.14. Found: C, 78.33; H, 8.08; N, 4.13.
22 27 2
(ꢀ)-threo-N-(Phenylpropyl) Methyl Phenyl(piperidin-2-yl)-
acetate (2B)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
0.16 g), 3-phenylpropionaldehyde (0.2 mL), and triethylamine (0.3 mL) in methanol
30 mL) was reductively alkylated by employing a method virtually identical to that
(
(
used for 2A, with the exception that an aqueous workup procedure was employed in
the isolation process. Addition of 1 M HCl in ether to a methanol solution of the
residue, evaporation of solvents to dryness in vacuo, and recrystallization (EtOAc–
ꢁ
1
hexane) provided 49 mg (55%) of 2B as white solid: 160–161 C; H NMR (CDCl ):
3
d 1.6–0.9 (m, 6H), 1.8–1.6 (t, 2H), 2.4 (m, 1H), 2.8–2.6 (m, 4H), 3.1–3.2 (m, 1H),
3
.4 (m, 1H), 3.61 (s, 3H, OCH ), 4.2–4.1 (d, 1H, J ¼ 10.4), 7.4–7.2 (m, 10H,
23 30 2
3
aromatic-H) ppm; MS-CI m=z 352.22, calcd. for C H NO (MHþ). Anal. calcd.
for C H NO : C, 78.64; H, 8.33; N, 3.98. Found: C, 78.65; H, 8.32; N, 3.98.
2
3
29
2
(
ꢀ)-threo-N-(Phenylbutyl) Methyl Phenyl(pieridin-2-yl)acetate (2C)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
(
0.172 g), 4-phenylbutyraldehyde (0.19 g, 0.001275 mol), and triethylamine (0.3 mL)
in methanol (30 mL) was reductively alkylated by employing a method virtually ident-
ical to that used for 2B, with the exception that an aqueous workup procedure was
employed in the isolation process. Addition of 1 M HCl in ether to a methanol sol-
ution of the residue, evaporation of solvents to dryness in vacuo, and recrystallization
ꢁ
1
(
EtOAc–hexane) gave 91 mg (82%) of 2C as a white solid: mp 140–141 C; H NMR
(CDCl ): d 1.6–0.9 (m, 6H), 1.8–1.6 (t, 4H), 2.4 (m, 1H), 2.6–2.58 (m, 4H), 3.1–3.2 (m,
3
1
H), 3.4 (m, 1H), 3.61 (s, 3H, OCH ), 4.2–4.1 (d, 1H, J ¼ 10.4), 7.4–7.2 (m, 10H,
24 32 2
3
aromatic-H), ppm; MS-CI m=z 366.3, calcd. for C H NO (MHþ). Anal. calcd.
for C H NO : C, 78.90; H, 8.56; N, 3.83. Found: C, 78.91; H, 8.55; N, 3.82.
4
2
31
2
(ꢀ)-threo-N-(Phenylpentyl) Methyl Phenyl(piperidin-2-yl)-
acetate (2D)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
(0.16 g), 5-phenylpentyraldehyde (0.2 g, 0.001275 mol), and triethylamine (0.3 mL) in
methanol (30 mL) was reductively alkylated by employing a method virtually

1740
B. OJO
identical to that used for 2B, with the exception that an aqueous workup procedure
was employed in the isolation process. Addition of 1 M HCl in ether to a methanol sol-
ution of the residue, evaporation of solvents to dryness in vacuo and recrystallization
ꢁ
1
(EtOAc-hexane) provided 81mg (87%) of 2D as a white solid: mp 136–137 C; H
NMR (CDCl ): d 1.6–0.9 (m, 6H), 1.8–1.7 (t, 4H), 2.4 (m, 1H), 2.5–2.2 (m, 4H), 2.6
3
(
7
t, 2H), 3.1–3.2 (m, 1H), 3.4 (m, 1H), 3.61 (s, 3H, OCH ), 4.2–4.1 (d, 1H, J ¼ 10.4),
3
.4–7.2 (m, 10H, aromatic-H) ppm; MS-CI m=z 380.25, calcd. for C H NO
25 34 2
(
MHþ). Anal. calcd. for C H NO : C, 79.15; H, 8.78; N, 3.68. Found: C, 79.17;
2
5
33
2
H, 8.77; N, 3.68.
(
ꢀ)-threo-N-(Phenylhexyl) Methyl Phenyl(piperdin-2-yl)acetate(2E)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
(
0.17 g), 6-phenylhexyraldehyde (0.23 g, 0.001275 mol), and triethylamine (0.3 mL)
in methanol (30 mL) was reductively alkylated by employing a method virtually
identical to that used for 2B, with the exception that an aqueous workup procedure
was employed in the isolation process. Addition of 1 M HCl in ether to a methanol
solution of the residue, evaporation of solvents to dryness in vacuo and recrystalliza-
ꢁ
1
tion (EtOAc–hexane) provided 95 mg (89%) of 2E as a white solid: mp 156–157 C; H
NMR (CDCl ): d 1.6–0.9 (m, 6H), 1.8–1.7 (t, 4H), 2.4 (m, 1H), 2.5–2.2 (m, 6H), 2.6 (t,
3
2
7
H), 3.1–3.2 (m, 1H), 3.4 (m, 1H), 3.61 (s, 3H, OCH ), 4.2–4.1 (d, 1H, J ¼ 10.4),
3
.4–7.2 (m, 10H, aromatic-H) ppm; MS-CI m=z 394.30, calcd. for C H NO
2
2
6
36
(
MHþ). Anal. calcd. for C H NO : C, 79.39; H, 8.98; N, 3.55. Found: C, 79.38;
2
6
35
2
H, 8.97; N, 3.54.
Synthesis of 2-Chloromethyl Pyridine
Pyridine-2-methanol (2 g, 0.018 mol) was added to SOCl (10 mL, cooled in an
2
ice bath) with stirring over a period of 15 min via a graduated glass funnel. After
the initial exothermic reaction has subsided, the reaction mixture was heated under
reflux for an additional 20 min. The solution obtained was cooled in an ice bath
ꢁ
and overlayed with an equal volume of petroleum ether (40–60 C boiling range)
(instead of ligroin). After vigorous scratching and stirring with a glass rod, the lower
layer was separated by filtration to give a light brown solid. The solid from the first
filtration was washed several times (with petroleum ether and diethyl ether) to remove
residual thionyl chloride. Addition of 1 M HCl in ether to a methanol solution of the
residue, evaporation of solvents to dryness in vacuo, and recrystallization (EtOH–
EtOAc, 1:1) provided 2.1 g (70%) of the titled compound as a light brown solid: mp
ꢁ
1
1
19–121 C. H NMR (CDCl ): consistent with the structure assigned to the product.
3
Synthesis of 3-Chloromethyl Pyridine
3-Chloromethyl pyridine was prepared from pyridine-3-methanol (2 g,
.018 mol) and SOCl (10 mL, cooled in an ice bath) employing a method virtually
0
2
identical to that used for 2-chloromethyl pyridine. Addition of 1 M HCl in ether to
a methanol solution of the residue, evaporation of solvents to dryness in vacuo, and
recrystallization (EtOH–EtOAc, 1:1) provided 2.3 g (72.5%) of the titled compound

METHYL PHENYL(PIPERYDIN-2-YL)ACETATE ANALOGS
1741
ꢁ
1
as a light brown solid: mp 140–143 C. H NMR (CDCl ): consistent with the
3
structure assigned to the product.
Synthesis of 4-Chloromethyl Pyridine
4
-Chloromethyl pyridine was prepared from pyridine-4-methanol (2 g,
.018 mol) and SOCl (10 mL, cooled in an ice bath) by a method virtually identical
0
2
to that employed to synthesize 2-chloromethyl pyridine. Addition of 1 M HCl in
ether to a methanol solution of the residue, evaporation of solvents to dryness in
vacuo, and recrystallization (EtOH–EtOAc, 1:1) provided 2.08 g (69.2%) of the titled
ꢁ
1
compound as a light brown solid: mp 160–162 C. H NMR (CDCl ): consistent with
3
the structure assigned to the product.
(ꢀ)-threo-N-(Methyl-2-thiopene) Methyl Phenyl(piperidin-2-yl)-
acetate (3A)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
(
0.260 g, 0.96 mmol) and thiopene-2-aldehyde (0.146 g, 0.11 mL, 1.3 mmol) was in
methanol (25 mL) was reductively alkylated employing a method virtually identical
to that used for 2A. Addition of 1 M HCl in ether to a methanol solution of the residue,
evaporation of solvents to dryness in vacuo, and recrystallization (EtOAc–hexane)
ꢁ
1
provided 150 mg (85%) of 3A as a yellow solid: mp 180–181 C; H NMR (CDCl ):
3
d 1.6–1.1 (m, 6H), 2.58–2.53 (m, 1H), 3.03–2.95 (m, 1H), 3.66–3.49 (m, 1H), 3.71 (s,
3
H, OCH ), 3.97–3.93 (d, 1H, J ¼ 13.4), 3.84–3.97 (d, 1H, J ¼ 13.2), 4.2–4.1 (d, 1H,
3
J ¼ 10.4), 6.9 (d, 1H, thiopene-H), 7.3 (dd, 2H, thiopene-H), 7.4–7.2 (m, 5H,
aromatic-H), ppm; MS-FBþ m=z 330.20, calcd. for C H NO S (MHþ). Anal. calcd.
1
9
24
2
for C H NO S: C, 69.31; H, 7.05; N, 4.25. Found: C, 69.32; H, 7.05; N, 4.25.
1
9
23
2
(ꢀ)-threo-N-(Methyl-3-thiopene) Methyl Phenyl(piperidin-2-yl)-
acetate (3B)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
0.260g, 0.96mmol) and thiopene-3-aldehyde (0.146g, 0.11mL, 1.3 mmol) in methanol
25 mL) was reductively alkylated by a method virtually identical to that used to syn-
(
(
thesize 3A. Addition of 1 M HCl in ether to a methanol solution of the residue, evap-
oration of solvents to dryness in vacuo, and recrystallization (EtOAc–hexane) provided
ꢁ
1
42 mg (80%) of 3B as a yellow solid: mp 175–176 C; H NMR (CDCl ): d 1.6–1.1 (m,
1
6
3
3
H), 2.58–2.53 (m, 1H), 3.03–2.95 (m, 1H), 3.66–3.49 (m, 1H), 3.71 (s, 3H, OCH3),
.97–3.93 (d, 1H, J ¼ 13.4), 3.84–3.97 (d, 1H, J ¼ 13.2), 4.2–4.1 (d, 1H, J ¼ 10.4), 7.1
(
s, 1H, thiopene-H), 7.4–7.2 (m, 5H, aromatic-H), 7.50 (d, 1H, thiopene-H), 7.60 (d,
1
calcd. for C H NO S: C, 69.31; H, 7.05; N, 4.25. Found: C, 69.32; H, 7.05; N, 4.26.
H, thiopene-H) ppm; MS-FBþ m=z 330.20, calcd. for C H NO S (MHþ). Anal.
1
9
24
2
19 23 2
(
(
ꢀ)-threo-N-Methyl-(5-chlorothiopene) Methyl Phenyl-
piperidin-2-yl)acetate (3C)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 2-chloro-5-(chloromethyl) thiopene (67 mg, 0.40 mmol) in acetone (20 mL) was

1742
B. OJO
alkylated by a method virtually identical to that employed to synthesize 1D. Addition
of 1 M HCl in ether to a methanol solution of the residue, evaporation of solvents to
dryness in vacuo and recrystallization (EtOAc–Hexane) provided 71 mg (68%) of 3C
ꢁ
1
as a brown solid: mp 171–173 C; H NMR (CDCl ): d 1.6–1.1 (m, 6H), 3.03–2.95
3
(
m, 1H), 2.77–2.60 (m, 1H), 3.59–3.42 (m, 1H), 3.70 (s, 3H, OCH ), 3.92–3.89 (d,
3
1
H, J ¼ 13.2), 4.10–4.02 (d, 1H, J ¼ 10.2), 6.75–6.05 (dd,21H, thiopene), 7.4–7.2 (m,
H, aromatic-H) ppm; MS-CI m=z 364.120 calcd. for C H NO S Cl (MHþ). Anal.
5
calcd. for C H NO SCl: C, 62.71; H, 6.11; N, 3.85. Found: C, 62.72; H, 6.10; N, 3.85.
1
9
23
2
1
9
22
2
(ꢀ)-threo-N-(Methyl-2-furan) Methyl Phenyl(piperidin-2-yl)-
acetate (3D)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
0.260 g, 0.96 mmol) and 2-furaldehyde (0.125 g, 0.11 mL, 1.3 mmol) was in methanol
25 mL) was reductively alkylated employing a method virtually identical to that
(
(
used for 2A. Addition of 1 M HCl in ether to a methanol solution of the residue,
evaporation of solvents to dryness in vacuo, and recrystallization (EtOAc–hexane)
ꢁ
1
provided 110 mg (88%) of 3D as a white solid: mp 170–171 C; H NMR (CDCl ):
3
d 1.6–1.1 (m, 6H), 2.58–2.53 (m,1H), 3.03–2.95 (m, 1H), 3.66–3.49 (m, 1H), 3.71
(
1
s, 3H, OCH ), 3.97–3.93 (d, 1H, J ¼ 13.4), 3.84–3.97 (d, 1H, J ¼ 13.2), 4.2–4.1 (d,
3
H, J ¼ 10.4), 6.4 (d, 1H, furan-H), 6.6 (d, 1H, furan-H), 7.4–7.2 (m, 5H,
aromatic-H), 7.58 (d, 1H, furan-H) ppm; MS-FBþ m=z 314.20, calcd. for
C H NO (MHþ). Anal. calcd. for C H NO : C, 72.84; H, 7.41; 4.46. Found:
1
9
24
3
19 23
3
C, 72.84; H, 7.40; N, 4.46.
(ꢀ)-threo-N-(Methyl-3-furan) Methyl Phenyl(piperidin-2-yl)-
acetate (3E)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate hydrochloride
0.260 g, 0.96 mmol) and 3-furaldehyde (0.125 g, 0.11 mL, 1.3 mmol) in methanol
25 mL) was reductively alkylated by a method virtually identical to that used to syn-
(
(
thesize 3D. Addition of 1 M HCl in ether to a methanol solution of the residue,
evaporation of solvents to dryness in vacuo, and recrystallization (EtOAc–hexane)
ꢁ
provided 102 mg (86%) of 3E as a white solid: mp 181–182 C; The hydrochloride salt
ꢁ
1
was recrystallized from EtOAc–hexane: mp 181–182 C; H NMR (CDCl ): d 1.6–1.1
3
(m, 6H), 2.58–2.53 (m, 1H), 3.03–2.95 (m, 1H), 3.66–3.49 (m, 1H), 3.71 (s, 3H,
OCH ), 3.97–3.93 (d, 1H, J ¼ 13.4), 3.84–3.97 (d, 1H, J ¼ 13.2), 4.2–4.1 (d, 1H,
3
J ¼ 10.4), 6.4 (s, 1H, furan-H), 6.6 (d, 1H, furan-H), 7.4–7.2 (m, 5H, aromatic-H),
7
Anal. calcd. for C H NO : C, 72.84; H, 7.41; N, 4.46. Found: C, 72.84; H, 7.40;
.50 (dd, 2H, furan-H) ppm; MS-FBþ m=z 314.20, calcd. for C H NO (MHþ).
19 23 3
1
9
24
3
N, 4.45.
(ꢀ)-threo-N-(2-Methylpyridyl) Methyl Phenyl(piperidin-2-yl)-
acetate (3F)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 2-chloro methyl pyridine (66 mg, 0.4 mmol) in acetone (20 mL) was alkylated by a

METHYL PHENYL(PIPERYDIN-2-YL)ACETATE ANALOGS
1743
method virtually identical to that used to synthesize 1D. Recrystallization of the dihy-
drochloride salt (EtOAc–hexane) provided 71.5 mg (87%) of 3F as a light brown solid:
ꢁ
1
mp 153–154 C; H NMR (CDCl ): d 1.6–1.1 (m, 6H), 2.58–2.53 (m, 1H), 3.03–2.95
3
(
(
m, 1H), 3.66–3.49 (m, 1H), 3.69 (s, 3H, OCH ), 3.96–3.91 (d, 1H, J ¼ 13.4), 3.79–3.75
3
d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.4), 7.1 (t, 1H, pyridyl-H), 7.3–7.2 (m, 9H,
aromatic-H), 7.4 (d, 1H, pyridyl-H), 7.8 (t, 1H, pyridyl-H), 8.45 (d, 1H, pyridyl-H)
ppm; MS-FBþ m=z 325.20 calcd. for C H N O (MHþ). Anal. calcd. for
2
0
25
2
2
C H N O : C, 74.08; H, 7.47; N, 8.63. Found: C, 74.07; H, 7.46; N, 8.63.
2
2
0
24
2
(ꢀ)-threo-N-(3-Methylpyridyl) Methyl Phenyl(piperidin-2-yl)-
acetate (3G)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.39 mmol)
and 3-chloromethyl pyridine (66 mg, 0.4 mmol) in acetone (20 mL) was alkylated by
employing a method virtually identical to that used for 3F. Recrystallization of the
dihydrochloride salt (EtOAc–hexane) provided 63 mg (78%) of 3G as a brown solid:
ꢁ
1
mp 159–160 C; H NMR (CDCl ): d 1.6–1.1 (m, 6H), 2.58–2.53 (m, 1H), 3.03–2.95
3
(
(
m, 1H), 3.66–3.49 (m, 1H), 3.69 (s, 3H, OCH ), 3.96–3.91 (d, 1H, J ¼ 13.4), 3.79–3.75
3
d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.4), 7.3–7.2 (m, 9H, aromatic-H), 7.4 (s, 1H,
pyridyl-H), 7.6 (d, 1H, pyridyl-H), 8.5 (d, 2H, pyridyl-H) ppm; MS-FBþ m=z 325.20
calcd. for C H N O (MHþ). Anal. calcd. for C H N O : C, 74.08; H, 7.47; N,
2
0
25
2
2
20 24
2
2
8
.63. Found: C, 74.07; H, 7.46; N, 8.62.
(ꢀ)-threo-N-(4-Methylpyridyl) Methyl Phenyl(piperidin-2-yl)-
acetate (3H)
A mixture of (ꢀ)-threo methyl phenyl(piperidin-2-yl)acetate (89 mg, 0.38 mmol)
and 4-chloro-methylpyridine (66 mg, 0.4 mmol) in acetone (20 mL) was alkylated by a
method virtually identical to that used to synthesize 3F. Recrystallization of the dihy-
drochloride salt (EtOAc–hexane) provided 78 mg (82%) of 3G as a brown solid: mp
ꢁ
40–141 C; H NMR (CDCl ): d 1.6–1.1 (m, 6H), 2.58–2.53 (m, 1H), 3.03–2.95
3
1
1
(
3
7
m, 1H), 3.66–3.49 (m, 1H), 3.69 (s, 3H, OCH ), 3.96–3.91 (d, 1H, J ¼ 13.4),
3
.79–3.75 (d, 1H, J ¼ 13.2), 4.18–4.14 (d, 1H, J ¼ 10.4), 7.3–7.2 (m, 9H, aromatic-H),
.4 (d, 2H, pyridyl-H), 8.5 (d, 2H, pyridyl-H) ppm; Ms-FBþ m=z 325.20 calcd. for
C H N O (MHþ). Anal. calcd. for C H N O : C, 74.08; H, 7.47; N, 8.63.
2
0
25
2
2
20 24
2
2
Found: C, 74.08; H, 7.46; 8.62.
(
ꢀ)-threo-N-Methylmethyl Phenyl(piperidin-2-yl)acetate (4)
A solution of 230 mg (0.99 mmol) of (ꢀ)-threo methyl phenyl(piperidin-2-yl)
acetate in 20 mL of methanol was treated with 0.095 mL (1.28 mmol) 37% HCHO
(formaldehyde) solution and allowed to stand at room temperature for 20 min.
Methanol (5 mL), acetic acid (0.03 mL), and 5% Pd=C (45 mg) were then added.
The resulting mixture was treated with hydrogen gas at 35 psi for 1.5 h at room tem-
perature. The mixture was filtered, and the filtrate and the washings were evaporated
in vacuo. The residue was mixed with 5 mL of water, made basic with 15% NaOH
solution, and extracted with EtOAc (3 ꢂ 100 mL). The extracts were combined,

1744
B. OJO
washed with water, dried with magnesium sulfate, and evaporated in vacuo. The
residue was chromatographed on 5 g of silica gel using 5% MeOH in chloroform to
give a yellow residue. Addition of 1 M HCl in ether to a methanol solution of the
residue, evaporation of solvents to dryness in vacuo, and recrystallization (EtOAc-
1
hexane) provided 190 mg (80%) of 4 as a yellow viscous liquid; H NMR (CDCl ):
3
d 1.6–1.1 (m, 6H), 2.40 (s, 3H, CH ), 2.98–2.90 (m, 1H), 2.59–2.42 (m, 1H),
3
3
.1–3.08 (m, 1H), 3.62 (s, 3H, OCH ), 3.88–3.73 (d, 1H), 7.4–7.2 (m, 5H, aromatic)
3
ppm; MS-CI m=z 248.160 calcd. for C H NO (MHþ) 248.165. Anal. calcd. for
1
5
22
2
C H NO : C, 72.87; H, 8.56; N, 5.67. Found: C, 72.85; H, 8.55; N, 5.68.
2
1
5
21
ACKNOWLEDGMENTS
The author thanks Gabrielle Jones, Shanet Goodwin, and Robersy Matute for
their assistance during the preparation of this manuscript and the National Institutes
of Health (NIH=NIGMS) for support of this work.
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