On the enantiomers of 2-dimethylamino-3-pentanone, key intermediates in the synthesis of analgesic alkylaminoalkylnaphthalenes

Article abstract of DOI:10.1016/S0957-4166(99)00223-2

2-Dimethylamino-3-pentanone 1 is the key intermediate in the synthesis of alkylaminoalkylnaphthalenic analgesics. In this paper the resolution of this compound with L- and D-dibenzoyltartaric acids is described The behavior of the diastereomeric dibenzoyltartrates and of the enantiomers in solution is investigated by NMR spectroscopy, polarimetry and chiral gas- chromatographic analysis.

Full text of DOI:10.1016/S0957-4166(99)00223-2

Pergamon
Tetrahedron: Asymmetry 10 (1999) 2387–2397
On the enantiomers of 2-dimethylamino-3-pentanone, key
intermediates in the synthesis of analgesic
alkylaminoalkylnaphthalenes
a,∗
b
a
a
Simona Collina, Francesca Benevelli, Dina Vercesi and Victor Ghislandi
a
Dipartimento di Chimica Farmaceutica, Università di Pavia, viale Taramelli, 12, I-27100, Pavia, Italy
b
Centro Grandi Strumenti, Università di Pavia, via Bassi, 21, I-27100, Pavia, Italy
Received 18 May 1999; accepted 3 June 1999
Abstract
-Dimethylamino-3-pentanone 1 is the key intermediate in the synthesis of alkylaminoalkylnaphthalenic anal-
2
gesics. In this paper the resolution of this compound with L- and D-dibenzoyltartaric acids is described. The
behavior of the diastereomeric dibenzoyltartrates and of the enantiomers in solution is investigated by NMR
spectroscopy, polarimetry and chiral gas-chromatographic analysis. © 1999 Published by Elsevier Science Ltd.
All rights reserved.
1. Introduction
Previous research on dialkylaminoalkyl- and cycloaminoalkylnaphthalenes led us to synthesize (Fig. 1)
1
1
-ethyl-1-[2-(6-hydroxynaphthyl)]-1-hydroxy-2-methyl-3-dimethylaminopropane B, 1,2-dimethyl-3-
2
[2-(6-hydroxynaphthyl)]-3-hydroxypyrrolidine C,
and 1,2-dimethyl-3-[2-(6-fluoronaphthyl)]-3-
3
hydroxypyrrolidine D, racemic (1R,2R/1S,2S)-B, (2R,3S/2S,3R)-C, (2R,3S/2S,3R)-D and optically
active (1R,2R)-B, (1S,2S)-B, (2R,3S)-C, (2S,3R)-C, (2R,3S)-D, (2S,3R)-D. These compounds are
structural analogues of 17-methyl-17-azaequilenine A (Fig. 1), the component with the strongest
analgesic properties of a group of phenolic heterosteroids.4 They show in vivo opioid-like analgesic
activity (hot plate test and writhing test) similar to those of peptide ligands, for which the role of the
topochemical features has already been emphasized.6
,5
–8
The study of the structure–activity relationships led us to synthesize 1-ethyl-1-[2-(6-
hydroxynaphthyl)]-1-hydroxy-2-methyl-2-dimethylaminoethane and 1-ethyl-1-[2-(6-fluoronaphthyl)]-
1
-hydroxy-2-methyl-2-dimethylaminoethane (Fig. 2, formulas A and B, respectively).9 The key
intermediate in the synthesis of these compounds is 2-dimethylamino-3-pentanone (ꢀ)-1 (Fig. 2).
∗
Corresponding author. E-mail: collina@chifar.unipv.it
0957-4166/99/$ - see front matter © 1999 Published by Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00223-2

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S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
Figure 1.
Figure 2.
Racemic and optically active compounds 1 have not been described in the literature. Jung and Love10
only mentioned the preparation of the racemate and did not report the experimental conditions or
chemical–physical properties. Moreover, in the literature only the resolution of cyclic α-amino-ketones
11
is described, in particular for bicyclic α-amino-ketones (Fig. 3A) and of 1,2-dimethyl-3-pyrrolidone
1
2
(
Fig. 3B). To the best of our knowledge the resolution of open chain α-amino-ketones with Cα as the
stereogenic center has never been reported.
Figure 3.
Since an anomalous behavior was observed during the resolution of compound 1, a detailed study
of this problem is of high interest. In this paper the synthesis and resolution of 2-dimethylamino-3-
pentanone is reported, and the behavior of the enantiomers of compound 1 is investigated by NMR
spectroscopy, polarimetric analysis and chiral GC analysis.
2. Results and discussion
Compound (ꢀ)-1 was prepared by reaction of 3-pentanone in methanol with bromine and water to
obtain (ꢀ)-2 and subsequent reaction of the latter with dimethylamine (Scheme 1).
The resolution of compound 1 was carried out via fractional crystallization using (−)-L-
dibenzoyltartaric acid monohydrate [(−)-L-DBTA·H O] and (+)-D-dibenzoyltartaric acid [(+)-D-DBTA]
2
as resolving agents. On salification of (ꢀ)-1 in ethanol with the appropriate dibenzoyltartaric acid,
a white solid precipitated (almost 70% of the formed salt). (−)-1 L-Dibenzoyltartrate monohydrate

S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
2389
Scheme 1.
2
3
[
(−)-1 L-DBT·H O] (mp 134–135°C, [α] =−113.3, (c 1, CH OH)) or (+)-1 D-dibenzoyltartrate
2
D
3
23
monohydrate [(+)-1 D-DBT·H O] (mp 134–135°C, [α] =+112.8, (c 1, CH OH)) was obtained with
2
D
3
only one crystallization from acetone/ethanol 50%. On further crystallization, both the specific rotatory
power and melting point remained unchanged. A single crystallization is thus sufficient to obtain
enantiomerically pure or almost pure salts.
This finding is ascribed (Scheme 2) to a tautomeric equilibrium in solution of 1 with the corresponding
enol. The disappearance of the stereogenic center C(2) in the enol allows the equilibrium between the two
diastereomeric salts. It is likely that during the crystallization the more soluble diastereomer transforms
into the less soluble and more stable diastereomer which crystallizes and leaves the system, thus causing
the partial interconversion of isomer I into isomer II.
Scheme 2.
A rapid decrease in the optical activity in methanol of (−)-1 L-DBT·H O (and analogously of (+)-
2
1
D-DBT·H O) was observed. Consequently, polarimetric measurements were always performed at 6
2
min after the sample dissolution (a convenient time to measure [α] ). A kinetic study of the optical
D
activity decay of (−)-1 L-DBT·H O was carried out (Fig. 4). The steady value of specific rotatory power
2
23
[
[α] =−95.8 (c 1, CH OH)] corresponds to the optical activity of the salt of (ꢀ)-1 with L-DBTA·H O.
D
3
2
This was verified by measuring the optical activity of a 1% methanolic solution of L-DBTA·H O and (ꢀ)-
2
1
in a 1:1 molar ratio solution. The value obtained was the same as that of a solution of (−)-1 L-DBT·H O
2
at the equilibrium. The chiral GC analysis of the base extracted from the latter solution confirmed the
racemization of the base.
A rapid decay of the optical activity of (−)-1 L-DBT·H O was also observed in 0.5% NaHCO aqueous
2
3
solution (Fig. 4), till a steady value of [α]D23=−93.5, attributable to a mixture of L-DBT sodium salt
and racemic 1. As for the methanolic solution, the [α]D23 of a 0.5% NaHCO aqueous solution of
3
(
−)-L-DBTA and racemic compound 1 gave the same value as that of a (−)-1 L-DBT·H O solution at
2
equilibrium. Thus, the diastereoisomeric dibenzoyltartrates in methanolic and aqueous basic solution
are optically unstable, owing to the racemization of the enantiomers of 1. Consequently, recovery of
the enantiomerically pure bases from the respective salts is a crucial method to establish. In order
to study the experimental conditions, preliminary trials on (−)-1 L-DBT·H O were performed. Two
2
extraction experiments were performed. In the first, methylene chloride and 0.5% NaHCO aqueous
3

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S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
Figure 4. Decay of optical activity of (−)-1 L-DBT·H
2 3
O in 0.5% aq. NaHCO and methanol
solution were used but the time from the addition of the aqueous solution was increased as shown in
Table 1. In the second, the base was always extracted at the same time (15 min), but solutions with
different amounts of NaHCO were used (Table 2). The enantiomeric excess (e.e.) was then evaluated
3
by chiral GC. The enantiomeric excess of the recovered base depends on the time (Table 1), but does
not depend on the concentration of the aqueous NaHCO solution (Table 2). Therefore, the extraction
3
of the bases was performed by treating the finely powdered salts with a mixture of methylene chloride
and saturated aqueous solution of sodium bicarbonate for not more than 15 min. Under these conditions
2
3
23
(
+)-1 [[α]D =+51.1 (c 1, CH Cl ), e.e.=83.1%] and (−)-1 [[α] =−51.9 (c 1, CH Cl ), e.e.=86.4%]
2
2
D
2
2
were obtained.
Table 1
Change of the e.e. of (−)-1 recovered from (−)-1 L-DBT·H
2
3
O with aq. NaHCO and extraction after
time indicated

S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
2391
Table 2
Enantiomeric excess of (−)-1 recovered from (−)-1 L-DBT·H
2
O with varying concentrations of aq.
and extraction after 15 min
NaHCO
3
The optical activity of compound 1 shows different behavior in the solution depending on the solvent.
In particular, it does not change in some hydrophobic organic solvents such as CH Cl and CH CN.
2
2
3
However, in hydrophilic solvents, such as alcoholic solvents or water a rapid decay of the optical activity
is observed (Fig. 5a–c). The rate of the decay decreases as the solvent hydrophilicity decreases. Moreover,
the curves in both methanol and ethanol display a maximum (Fig. 5a,b) in the first 30 min of the sample
dissolution.
To explain the behavior of optically active 1 in solution, H NMR (500 MHz) and 13C NMR (125.76
1
MHz) studies on various conditions were performed.
1
The H NMR spectra, recorded in deuterated methanol at different times, show a decrease in the
intensity of the peaks at 2.97 and 2.46 ppm (Table 3), assigned to CH(2) and CH (4), respectively.
2
These data reveal the presence of two keto-enolic equilibria involving the CH(2) and CH (4) protons.
2
These tautomeric equilibria in deuterated solvents allow the progressive incorporation of deuterium in the
1
molecule with consequent decrease of the H signals. Since the decrease of the signal intensity is directly
related to the kinetics of the reactions, enol B (Fig. 6) proved to be the preferred one.13 The formation of
this enol is responsible for the racemization.
13C NMR spectra were also registered in deuterated methanol at different times. The spectrum obtained
immediately after sample dissolution, shows two signals at 69.69 and 11.86 ppm for C(2) and C(1),
respectively. After 12 h (at the equilibrium) the spectrum presents additional chemical shifts for both C(2)
and C(1), at 69.11 and 12.06 ppm, respectively. These new peaks were attributed to a partial deuteration
of CH(2) (Fig. 7) confirming the prevalent formation of the enol B, since there is no evidence of an
1
3,14
isotopic substitution at C4. Similar H/D isotopic substitutions have already been observed in ketones
and β-diketones.
15,16
Moreover, the faster kinetics of the decay of compound (+)-1 in 0.5% NaHCO aqueous solution
3
(Fig. 5d) compared to water (Fig. 5c) suggest that the tautomerism involving the CH(2) atom (responsible
for the racemization) is base-promoted by abstraction of the hydrogen α to the carbonyl group. Thus, the
racemization for compound 1 was faster in comparison to that for the dibenzoyltartrates.
NMR studies were performed to explain the maximum observed for the rotatory power of optically
active 1 versus time in methanol and ethanol. This can be explained by the formation of a ketal. There is
no direct NMR evidence of the presence of this species, probably because the reaction kinetics are too
fast on the NMR timescale. However, it is possible to prove the formation of the ketal indirectly. In both
A and D molecules (Fig. 6) the CH (4) protons are the AB part of an ABX system; therefore, a complex
2
3
1
multiplet is expected. A H NMR spectrum recorded immediately after the dissolution of the sample in
deuterated methanol shows a complex multiplet (the enlarged CH (4) signal is reported in Fig. 8a). At
2

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S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
Figure 5. Decay of optical activity of (+)-1 or (−)-1 in different solvents
1
equilibrium the H NMR spectrum is simplified: the CH (4) signal resulted in a simple quartet (Fig. 8b)
2
due only to the coupling of CH (4) with methyl CH (5). It is suggested that the asymmetry induced at
2
3
methylene 4 by the CH(2) is stronger in the ketal than in the ketone. Hence, it can change the appearance
of the spectra. To study how the formation of the ketal affects the appearance of the signal, the sample
1
was dissolved in an inert solvent (CD CN) and different H NMR spectra were obtained after addition of
3
an increasing amount of ethylene glycol (well known to give stable cyclic ketals). The signal of CH (4)
2
in CD CN is a simple quartet (Fig. 9c), which changes gradually into a complex multiplet with the
3
increase of the percentage of ethylene glycol in solution (Fig. 9a). This signal is similar to the multiplet
attributed to the CH (4) in CD OD, recorded immediately after the dissolution of the sample (Fig. 8a).
2
3
This similarity is consistent with the formation of the ketal D.

S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
2393
Table 3
1
Intensity changes with time in the H NMR of (−)-1 in CD
3
OD
Figure 6.
3. Experimental
3.1. General
Melting points: uncorrected; Büchi Tottoli apparatus. Elemental analyses: Carlo Erba 1106 C-, H-,
N-analyzer. TLC: 0.2 mm thick silica gel plates (Merck Kieselgel GF 254); detection of compounds with
−1
UV light. IR: Perkin–Elmer Mod. 682 spectrophotometer; only noteworthy absorptions are given in cm .

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S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
Figure 7. 13C NMR spectrum of (+)-1 after 12 h in CD
OD
3
1
Figure 8. H NMR spectra of (+)-1 in CD
3
OD
13
1
1
NMR: Hitachi R 1200 ( H 60 MHz), Bruker AMX 400 ( H 400 MHz, C 100.617 MHz) or on a Bruker
1
13
DRX 500 ( H 500 MHz, C 125.76 MHz) apparatus. Chemical shifts (δ) are reported in ppm relative
to TMS (δ=0.00) and coupling constants (J) in hertz. Optical rotations: Jasco DIP-1000 photoelectric
polarimeter (1 dm cell, sodium or mercury lamp); all measurements in methanol were recorded at 6
min from the dissolution of the sample (see results and discussion). Gas chromatography (GC): DANI
3800 apparatus; equipped with PTV and FID. [Method A: fused silica capillary column (DB-5, J and
W) (nonpolar liquid phase, film thickness, 0.25 µm; 15 m×0.25 mm i.d.); carrier gas: helium (flow

S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
2395
1
Figure 9. H NMR spectra (H
c) 1:20
4 3
signal) in CD CN of (+)-1 and ethylene glycol, in the following molar ratios: (a) 1:40, (b) 1:30,
(
rate, 45–48 cm/sec); oven and detector temperatures: 80 and 250°C, respectively; injection volume:
µl. Method B: permethylated β-cyclodextrin capillary column (β-DEX 120, Sulpelco) (nonbonded,
1
film thickness, 0.25 µm; 30 m×0.25 mm i.d.); carrier gas: helium (flow rate, 48–52 cm/sec); detector
temperature: 250°C; oven temperature: 80°C for 8 min and then 3°C/min till 120°C; injection volume:
1
µl.] All the reagents and solvents were obtained from commercial suppliers (Carlo Erba Reagenti and
Fluka). Methanol was dried on molecular sieves (diameter 4 Å). Standard vacuum techniques were used.
3.2. (ꢀ)-2-Bromo-3-pentanone (ꢀ)-2
CAUTION! This preparation must be carried out in a efficient hood; α-bromo ketones are highly
1
7
18
lachrimatory and are skin irritants. Compound (ꢀ)-2 was essentially prepared according to Gaudry
17
and Marquet for the preparation of 1-bromo-3-methyl-2-butanone. Starting from 3-pentanone (215.6 g,
2
.5 mol) and bromine (400.0 g, 2.5 mol), crude (ꢀ)-2 as a yellow oil (388.9 g, yield 94.1%) was obtained.
It was purified by fractional distillation in the dark, under reduced pressure and under nitrogen, to obtain
a colorless oil (287.7 g, yield 69.6%); bp 65–66°C. IR (film): 3400, 1720, 1440, 1310, 1100, 900, 750;
30
1
H NMR (60 MHz, in CDCl ) δ: 1.12 (t, 3H, CH CH ), 1.75 (d, 3H, CH CH), 2.70 (q, 2H, CH CO),
3
3
2
3
2
4
.4 (q, 1H, CHCO).
3.3. (ꢀ)-2-Dimethylamino-3-pentanone (ꢀ)-1
A mixture of (ꢀ)-2 (287.7 g, 1.7 mol) in absolute ethanol (800 mL), anhydrous Na CO (101.6 g, 1.0
2
3
mol) and 5.6 M dimethylamine in absolute ethanol (311 mL, 1.7 mol) was stirred under nitrogen. The
temperature was gradually increased to 50°C and this temperature was maintained for 16 h. After this
time the reaction mixture was filtered and the solvent removed. The resulting yellow oil was dissolved
in water (100 mL) and then extracted with ethyl ether (5×200 mL). The combined organic extracts were
dried over anhydrous Na SO and evaporated to yield crude (ꢀ)-1 as a yellow oil [91.0 g, yield 40.4%;
2
4
purity 91.7% (GC, method A)]. This was purified by fractional distillation in the dark, under reduced
pressure and under nitrogen to obtain a colorless oil [71.5 g, yield 31.5%; purity 99.99% (GC, method
A, t 3.6 min)], bp40 63–64°C. IR, film: 2820, 2770, 1720, 1440, 1370, 1260, 1150, 1040, 940, 800;
ret
1
H NMR (400 MHz, in CDCl ) δ: 1.02 (t, 3H, CH CH , J=7.0); 1.06 (d, 3H, CH CH, J=7.0); 2.18
3
3
2
3
(
s, 6H, N(CH ) ); 2.46 (dq, 2H, CH CO, J=2.5, 7.0); 2.97 (q, 1H, CHCO, J=7.0). TLC: hexane/ethyl
3 2 2
acetate/(C H ) NH 77/33/4 (v/v/v), R =0.68. Anal. calcd for C H NO: C, 65.07; H, 11.70; N, 10.84.
2
5 2
f
7
15
Found: C, 65.19; H, 11.75; N, 10.71.

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S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
3.4. Resolution of rac-2-dimethylamino-3-pentanone (ꢀ)-1
3
.4.1. With (−)-L-dibenzoyltartaric acid·H O
2
Compound (ꢀ)-1 (20 g, 0.16 mol) was added dropwise to a warmed solution (60°C) of (−)-L-
20
dibenzoyltartaric acid·H O [58.25 g, 0.16 mol, [α] =−110.5 (c 8.93, C H OH)] in ethanol (100
2
D
2
5
mL). The solution was slowly cooled to room temperature in the dark and (−)-2-dimethylamino-3-
pentanone L-dibenzoyltartrate monohydrate [(−)-1 L-DBT·H O] (53.80 g) precipitated as white needles,
2
23
19
mp 132–134°C, [α]D =−103.7 (c 1, CH OH), e.e.=64.1% (GC, Method B). On recrystallization (etha-
3
2
3
nol:acetone, 50:50) (540 mL), (−)-1 L-DBT·H O (40.80 g) was obtained; mp 134–135°C, [α] =−113.3
2
D
19
(
c 1, CH OH). On further crystallization both specific rotatory power and melting point remained
3
1
unchanged. H NMR (400 MHz, in CD OD, immediately after the dissolution of the sample) δ: 1.07
3
(
t, 3H, CH CH , J=7.0); 1.55 (d, 3H, CH CH, J=7.0); 2.60 (dq, 2H, CH CO, J=7.0–15.0); 2.82 (s, 6H,
3 2 3 2
1
N(CH ) ); 4.20 (q, 1H, CHCO, J=7.0); 5.9 (s, 2H, CHCOOH); 7.4–8.1 (10H, arom). In the H NMR
3
2
spectrum recorded after 12 h from the sample dissolution, the signal at 4.20 ppm disappeared and the
intensity of the signal at 2.60 ppm dramatically decreased. Anal. calcd for C H NO·C H O ·H O:
7
15
18 14
8
2
C, 59.40; H, 6.18; N, 2.77. Found: C, 59.62; H, 6.22; N, 2.72.
By recrystallization (ethanol:acetone, 50:50) of the product recovered from the mother liquors, another
2
3
19
amount (15.6 g) of (−)-1 L-DBT·H O was obtained; mp 134–135°C, [α] =−113.3 (c 1, CH OH).
2
D
3
By heating (−)-1 L-DBT·H O at 80°C under vacuum for 24 h, anhydrous (−)-1 L-DBT was obtained;
2
23
19
mp 135–137°C, [α]D =−117.1 (c 1, CH OH). Anal. calcd for C H NO·C H O : C, 61.59; H, 6.00;
3
7
15
18 14
8
N, 2.87. Found: C, 61.54; H, 6.23; N, 2.71.
3
.4.2. With anhydrous (+)-D-dibenzoyltartaric acid
According to the procedure described above, starting from 40.00 g of (ꢀ)-1 (0.30 mol) and 110.90
g (0.30 mol) of anhydrous (+)-D-dibenzoyltartaric acid [[α]D20=+116.0 (c 8.93, C H OH)], 93.1 g of
2
5
(
+)-2-dimethylamino-3-pentanone D-dibenzoyltartrate monohydrate [(+)-1 D-DBT·H O] was obtained
2
23
19
as white needles; mp 134–135°C, [α]D =+112.8 (c 1, CH OH). From the mother liquor an additional
3
23
19
amount (13.2 g) of (+)-1 D-DBT·H O was obtained; mp 134–135°C, [α] =+111.9 (c 1, CH OH).
2
D
3
1
H NMR spectrum: identical with that of the enantiomer. Anal. calcd for C H NO·C H O ·H O: C,
7
15
18 14
8
2
5
9.40; H, 6.18; N, 2.77. Found: C, 59.28; H, 5.96; N, 2.80.
By heating (+)-1 D-DBT·H O under the same conditions described for (−)-1 L-DBT·H O, anhydrous
2
2
23
19
(
+)-1 D-DBT was obtained; mp 135–137°C, [α]D =+116.9 (c 1, CH OH). Anal. calcd for C H NO
3
7
15
C H O : C, 61.59; H, 6.00; N, 2.87. Found: C, 61.75; H, 6.27; N, 2.78.
18
14
8
3.5. (+)-2-Dimethylamino-3-pentanone (+)-1
A saturated aqueous solution of NaHCO (15 mL) was added to a suspension of 2.5 g of finely
3
23
19
powdered (−)-1 L-DBT·H O [[α] =−113.3 (c 1, CH OH) ] in CH Cl (25 mL) under magnetic
2
D
3
2
2
stirring. Stirring was maintained for 15 min. The organic layer was immediately separated from the
aqueous one and dried on anhydrous Na SO . The solvent was removed to give 0.6 g of (+)-1 as a
2
4
2
3
23
23
colorless oil, [α]D =+51.1 (c 1, CH Cl ), [α] =+23.6 (c 1, C H OH, t=5 min), [α]
=+45.2 (c 1,
2
2
D
2
23
5
365
23
CH OH, t=5 min), [α]
=−25.6 (c 1, H O, t=5 min), [α]
=−71.4 (c 1, 0.5% NaHCO , t=5 min),
3
365
2
365
3
1
e.e.=83.1% (GC, Method B: tret 18.6 min, α=0.96, R =3.4). IR and H NMR spectra: identical with those
s
of (ꢀ)-1. Anal. calcd for C H NO: C, 65.07; H, 11.70; N, 10.84. Found: C, 64.93; H, 11.60; N, 10.72.
7
15

S. Collina et al. / Tetrahedron: Asymmetry 10 (1999) 2387–2397
2397
By further extraction of the aqueous phase with CH Cl (6×10 mL) an additional amount (0.1 g) of
2
2
(
+)-1 with lower optical activity was recovered, [α]D23=+11.5 (c 1, CH Cl ), e.e.=13.7% (GC, Method
2
2
B). Compound (+)-1 has to be stored at a temperature <4°C.
3.6. (−)-2-Dimethylamino-3-pentanone (−)-1
Applying the same procedure used for the enantiomer, and starting from 2.5 g of [(+)-1 D-DBT·H O
2
23
23
[
(
[α] =+112.8 (c 1, CH OH)], 0.6 g of (−)-1 were obtained: [α] =−51.9 (c 1, CH Cl ), e.e.=86.4%
D
3
D
2
2
1
GC, Method B: tret 17.6 min, α=0.96, R =3.4). IR and H NMR spectra: identical with those of (ꢀ)-1.
s
Anal. calcd for C H NO: C, 65.07; H, 11.70; N, 10.84. Found: C, 64.89; H, 11.55; N, 10.63. Compound
7
15
(−)-1 has to be stored at a temperature <4°C.
Acknowledgements
This research was supported by Grants from Italian ‘Ministero dell’Università e della Ricerca Scien-
tifica e Tecnologica’. The authors are very grateful to Biosearch Italia-Gerenzago (VA) for the use of
Bruker DRX 500 apparatus.
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9. t=6 min, see results and discussion.