Scalable Synthesis of N-Acetylated α-Amino Acid-Derived Oxazoline Ligands

Article abstract of DOI:10.1002/jhet.3468

A scalable cost-effective synthesis of promising α-amino acid-derived oxazoline ligands has been developed. The advantage of the reported procedures is the use of crystallization for the purification of key intermediates and final products. The ligands obtained have recently demonstrated remarkable enantioselectivity in Pd (II) catalyzed C─H activation reactions. Hence, more rational synthetic route presented here will contribute to this rapidly growing field of chemistry.

Full text of DOI:10.1002/jhet.3468

Month 2019
Scalable Synthesis of N-Acetylated α-Amino Acid-Derived
Oxazoline Ligands
Vitaly Kovalenkoa,b
and Kiryl Vasiutovichb
*
aDepartment of Chemistry, Belarusian State University, Nezavisimosty Avenue, 4, 220030 Minsk, Belarus
bDepartment of Natural Science, Belarusian State Pedagogical University, Sovetskaya Street, 18, 220030 Minsk, Belarus
*E-mail: kovalenkovn@rambler.ru
Received November 4, 2018
DOI 10.1002/jhet.3468
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
A scalable cost-effective synthesis of promising α-amino acid-derived oxazoline ligands has been
developed. The advantage of the reported procedures is the use of crystallization for the purification of
key intermediates and final products. The ligands obtained have recently demonstrated remarkable
enantioselectivity in Pd (II) catalyzed C─H activation reactions. Hence, more rational synthetic route
presented here will contribute to this rapidly growing field of chemistry.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
product triphenylphosphine oxide. In addition, careful
execution of this step is necessary to prevent the side
reactions [7,8]. Removal of Fmoc protecting group
proceeded smoothly, while oxazoline ring was well
tolerated under the reaction condition. However, this step
was also followed by column chromatography due to an
inevitable presence of Fmoc decomposition products.
A short survey of the literature revealed that the amide
coupling and the ring closure reactions could be carried
out separately [9–13], and this seems to be more effective
for bulk synthesis of oxazolines. We have chosen N-Boc-
protected α-amino acids as a starting material, which is
more compatible with the “atom economy” concept,
given that the Boc protection should be removed prior
closing an acid-sensitive oxazoline ring. Direct coupling
N-acetyl protected α-amino acids is impossible because of
a rapid racemization of the activated acid intermediate
[14]. Conversely, α-amino acid derivatives 2 N-Boc-L-
α-tert-butylglycine, N-Boc-L-valine, and N-Boc-D-valine
were successfully coupled with near equimolar
Oxazoline ligands constitute a diverse family of
chemical structures, which are widely used in the
different types of asymmetric transformation [1–3].
Recently published papers [4,5] renewed interest to these
classic molecules. Yu group specializing in C─H
activation reactions introduced bidentate N-acetylated
oxazoline-type ligands 1 (Scheme 1) prepared from α-
amino acids and β-amino alcohols. Pioneering procedures
for
a
remote enantioselective functionalization of
prochiral substrates [4,5] as well as kinetic resolution [5]
in the presence of palladium (II) catalysts and previously
mentioned oxazolines have been developed.
Remarkable enantioselectivity achieved may stimulate
further applications of this type of chiral molecules,
including industrially relevant transformations [4].
Bearing in mind an emerging interest to the С─H
activation chemistry and prospects of α-amino acid-
derived oxazolines [6], we focused on the developing
their cost-effective and scalable synthesis.
amounts of β-amino alcohols
3
L-valinol, L-
phenylalaninol [11] using ethyl chloroformate as
activating regent (Scheme 3).
RESULTS AND DISCUSSION
Further, Boc-protected coupling products 4a–e were
converted into acetamides 5a–e in a one-pot manner.
Once the removal of Boc group with trifluoroacetic acid
was completed, the solvent and volatile parts were
simply evaporated and the residue was treated with
potassium carbonate and one equivalent of acetic
anhydride. Mono-acetylated products were successfully
obtained [15]. Thereby, we avoided handling with
highly polar and water soluble unprotected amino
We started preparation of oxazolines 1 from examining
the Yu group’s procedure [5]. They utilized one-step
annulation method with the reagents Ph3P and CCl4 to
convert N-Fmoc-protected α-amino acids directly to
oxazolines (Scheme 2). Despite a sufficiently good yield,
tedious chromatography was required in order to separate
oxazoline from a large amount of the other reaction
© 2019 Wiley Periodicals, Inc.

V. Kovalenko and K. Vasiutovich
Vol 000
Scheme 1. Examples of enantioselective C─H activation reactions in the presence of α-amino acid-derived oxazoline ligands.
Scheme 2. Synthesis of oxazolines according to Shao et al. [5].
alcohols. Good crystallinity of N-acetyl derivatives 5 was
crucial for their successful separation from the impurities
with close Rf. According to our observation, acetonitrile
CONCLUSION
We developed a scalable three-step synthesis of
promising bidentate oxazoline ligands starting from Boc-
protected α-amino acids and unprotected β-amino
alcohols. The advantage of this scheme is an effective
use of routine crystallization for the isolation of key
intermediates and final products in most cases. Rational
synthetic approach can help to expand the application of
these recently introduced ligands.
could be
a
solvent of choice, which allows
recrystallizing 5 without a considerable yield loss.
Gelation of the mixture occurred with some amides.
Fortunately, this undesirable process can be suppressed
by adding a small amount of water to acetonitrile or by
switching a solvent.
Finally, compounds 5a–e were treated with
methanesulfonyl chloride in THF in the presence of the
excess of triethylamine and catalytic amount of p-
dimethylaminopyridine that lead to the almost pure
oxazolines 1a–e. A slightly increased temperature was
required for complete conversion of less soluble amides
5a,c. In most cases, final products 1 were easily purified
by recrystallization from appropriate solvent or by
vacuum sublimation.
EXPERIMENTAL
Melting points were determined on
a capillary
apparatus. Optical rotations were measured with an
ATAGO AP-300 polarimeter. Elemental analyses were
performed using Thermo Scientific TM Flash 2000
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Scalable Synthesis of N-Acetylated α-Amino Acid-Derived Oxazoline Ligands
Scheme 3. Synthesis of oxazolines.
CHNS/O analyzer. IR spectra were recorded on a Vertex
were added subsequently via syringe, and the stirring was
continued for 30 min, whereupon a solution of L-
phenylalaninol (8.24 g, 54.5 mmol) in THF (60 mL) was
added dropwise to the reaction. The mixture was
additionally stirred for 2 h, the cooling bath was
removed, and the solvent was evaporated in vacuo. Ethyl
acetate (300 mL) and the saturated solution of NH4Cl
(300 mL) were added to the residue, and the biphasic
mixture was heated with stirring until all solids were
dissolved. Organic and aqueous layers were separated,
and the aqueous layer was additionally extracted with
warm ethyl acetate (2 × 150 mL). Combined organic
extracts were washed with 40% aqueous solution of
K2CO3 (100 mL), dried with Na2SO4, and evaporated
under reduced pressure. The residue was recrystallized
from acetonitrile giving pure amide 4a as colorless
1
70 spectrometer. H NMR and 13C NMR spectra were
recorded at 500 and 125 MHz, respectively, on a Bruker
Avance 500 spectrometer in solvent DMSO-d6. Chemical
shifts were referred to the signals of the residual DMSO
1
(δ = 2.50 ppm in H NMR and δ = 39.52 ppm in 13C
NMR). TLC analysis was performed on Silica gel 60 F
254 plates; column chromatography was performed on
silica gel 70–230 mesh. β-Amino alcohols and Boc-
protected α-amino acids were purchased from Chem-
Impex Intl. Tetrahydrofuran and triethylamine were
freshly distilled from sodium, dichloromethane was
distilled from calcium hydride, and ethyl acetate was
dried with calcium chloride and distilled.
Synthesis of compounds 4a–e. Compounds 4a–e were
prepared by coupling Boc-protected α-amino acids 2 with
crystals, yield 14.0 g (73%), mp 200–205°C; [α]
β-amino alcohols
3 in accordance with common
20
= À59.5 (c = 1.2 in MeOH); IR (KBr): 3334, 3253,
procedure [11], except that isopropyl chloroformate was
replaced with ethyl chloroformate. For compound 4a,
reported procedure [11] was slightly modified (see
succeeding texts). Compounds 4b and 4c were used
without purification.
D
1680, 1633, 1562 cmÀ1; H NMR (DMSO-d6): δ 7.73 (d,
1
1H, NH, J = 8.3 Hz,), 7.26–7.12 (m, 5H, Ph), 6.29 (d,
1H, NHBoc, J = 9.7 Hz), 4.78 (app. t, 1H, OH,
J = 5.3 Hz), 4.01–3.86 (m, 1H, CHCH2OH), 3.79 (d, 1H,
CHtBu, J = 9.7 Hz), 3.36–3.32 (m, 1H, CH2OH), 3.30–
3.23 (m, 1H, CH2OH), 2.86 (dd, 1H, CH2Ph, J = 13.8,
5.4 Hz), 2.61 (dd, 1H, CH2Ph, J = 13.8, 8.6 Hz,), 1.38 (s,
9H, OtBu), 0.82 (s, 9H, tBu); 13C NMR (DMSO-d6): δ
169.8 (C), 155.2 (C), 139.1 (C), 129.1 (2CH), 128.0
(2CH), 125.9 (CH), 78.0 (C), 62.6 (CH), 62.0 (CH2),
tert-Butyl[(1S)-1-{[(1S)-1-benzyl-2-hydroxyethyl]carbamoyl}-
2,2-dimethylpropyl]carbamate (4a).
A vigorously stirred
solution of Boc-L-α-tert-butylglycine (12.15 g,
52.5 mmol) in THF (150 mL) was cold in an ice-salt bath
to the temperature À15°C. N-Methylmorpholine (5.66 g,
56.0 mmol) and ethyl chloroformate (5.79 g, 53.3 mmol)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. Kovalenko and K. Vasiutovich
Vol 000
52.2 (CH), 36.3 (CH2), 33.9 (C), 28.2 (3CH3), 26.6
(3CH3). Anal. Calcd for C20H32N2O4: C, 65.91; H, 8.85.
Found: C, 66.05; H, 8.96.
CHCH2OH), 3.35–3.32 (m, 2H, CH2OH), 1.87 (s, 3H,
CH3CO), 1.84–1.75 (m, 1H, CHMe2), 0.90 (s, 9H, tBu,
J = 7.6 Hz), 0.82 (d, 3H, CHMe2, J = 6.8 Hz), 0.80 (d,
3H, CHMe2, J = 6.8 Hz); 13C NMR (DMSO-d6): δ 170.1
(C), 169.0 (C), 61.4 (CH2), 59.8 (CH), 55.4 (CH), 34.0
(C), 28.1 (CH), 26.8 (3CH3), 22.5 (CH3), 19.6 (CH3),
17.9 (CH3). Anal. Calcd for C13H26N2O3: C, 60.44; H,
10.14. Found: C, 60.58; H, 10.10.
General procedure for compounds 5a–e. Trifluoroacetic
acid (40 mL) was added to a stirred and ice-cooled solution
of Boc-protected derivative 4 (38.0 mmol) in CH2Cl2
(350 mL). The ice bath was removed, and the stirring
was continued at room temperature for 2 h after which
the solvent was evaporated in vacuo. The resulting
residue was dissolved in ethyl acetate (380 mL), and
anhydrous powdered K2CO3 (27.6 g, 200 mmol) was
added portionwise. The mixture was placed in the ice
bath, and a solution of acetic anhydride (3.88 g,
38.0 mmoL) in ethyl acetate (30 mL) was added
dropwise to the vigorously stirred mixture. The stirring
was continued for 1 h in the ice bath and for 15 min at
room temperature, and then brine (500 mL) was added.
Two-phase mixture was heated to prevent crystallization
of the product and quickly transferred to the separatory
funnel. The layers were separated, and the aqueous layer
was extracted with ethyl acetate (5 × 100 mL). Combined
organic phases were dried over Na2SO4 for several
minutes, filtrated, and evaporated in vacuo. The residue
was recrystallized from an appropriate solvent to afford
pure acetyl derivatives 5.
(2S)-2-(Acetylamino)-N-[(1S)-1-benzyl-2-hydroxyethyl]-3-
methylbutanamide (5c).
Recrystallized from acetonitrile
containing 5% of water as colorless crystals, yield: 7.18 g
(65%), mp 187–191°C; [α]2D0 = À55.1 (c = 1.3 in
MeOH); IR (KBr): 3335, 1661, 1632, 1565, 1521 cmÀ1
;
1H NMR (500 MHz): δ 7.79 (d, 1H, NHAc, J = 9.0 Hz),
7.76 (d, 1H, NH, J = 8.4 Hz), 7.26–7.14 (m, 5H, Ph),
4.76 (app. t, 1H, OH, J = 5.3 Hz), 4.08 (dd, 1H, CHiPr,
J = 9.0, 7.3 Hz), 3.97–3.82 (m, 1H, CHCH2OH), 3.36–
3.31 (m, 1H, CH2OH), 3.29–3.21 (m, 1H, CH2OH), 2.86
(dd, 1H, CH2Ph, J = 13.7, 5.4 Hz), 2.60 (dd, 1H, CH2Ph,
J = 13.7, 8.5 Hz), 1.90–1.85 (m, 1H, CHMe2), 1.84 (s,
3H, CH3CO), 0.80–0.76 (m, 6H, CHMe2); 13C NMR
(DMSO-d6): δ 170.7 (C), 169.1 (C), 139.1 (C), 129.2
(2CH), 128.1 (2CH), 125.9 (CH), 62.5 (CH2), 57.8 (CH),
52.3 (CH), 36.4 (CH2), 30.4 (CH), 22.5 (CH3), 19.2
(CH3), 18.2 (CH3). Anal. Calcd for C16H24N2O3: C,
65.73; H, 8.27. Found: C, 65.55; H, 8.26.
The yields of 5a,d,e are given to 38.0 mmol of starting
material 4a,d,e; the yields of 5b and 5c are given to
38.0 mmol of N-Boc-L-α-tert-butylglycine and N-Boc-L-
valine.
(2S)-2-(Acetylamino)-N-[(1S)-1-(hydroxymethyl)-2-
methylpropyl]-3-methylbutanamide (5d).
Recrystallized
from acetonitrile as colorless crystals, yield 6.48 g (70%),
mp 192–196°C; [α]2D0 = À43.5 (c = 1.0 in MeOH); IR
(2S)-2-(Acetylamino)-N-[(1S)-1-benzyl-2-hydroxyethyl]-3,3-
1
(KBr): 3383, 3294, 1629, 1566, 1547 cmÀ1; H NMR
dimethylbutanamide (5a).
Recrystallized from tert-butyl
(DMSO-d6): δ 7.86 (d, J = 8.9 Hz, 1H, NHAc), 7.47 (d,
J = 9.1 Hz, 1H, NH), 4.49 (app. t, 1H, OH, J = 5.3 Hz),
4.13 (dd, 1H, CHNHAc, J = 8.9, 7.4 Hz), 3.63–3.51 (m,
1H, CHCH2OH), 3.39–3.30 (m, 2H, CH2OH), 1.97–1.89
(m, 1H, CHMe2), 1.85 (s, 3H, CH3CO), 1.83–1.77 (m,
1H, CHMe2), 0.85–0.81 (m, 9H, 2CHMe2), 0.80 (d, 3H,
CHMe2, J = 6.8 Hz); 13C NMR (DMSO-d6): δ 171.0 (C),
169.1 (C), 61.4 (CH2), 58.0 (CH), 55.4 (CH), 30.3 (CH),
28.1 (CH), 22.5 (CH3), 19.6 (CH3), 19.3 (CH3), 18.4
(CH3), 18.0 (CH3); Anal. Calcd for C12H24N2O3: C,
58.99; H 9.90. Found: C, 58.80; H, 9.90.
methyl ether as colorless crystals, yield 6.93 g (60%), mp
116–120°C; [α]2D0 = À56.9 (c = 1.3 in MeOH); IR (KBr):
1
3327, 1662, 1633, 1566, 1518 cmÀ1; H NMR (DMSO-
d6): δ 7.84 (d, 1H, NH, J = 8.4 Hz), 7.72 (d, 1H, NHAc,
J = 9.7 Hz), 7.25–7.11 (m, 5H, Ph), 4.74 (app. t, 1H,
OH, J = 5.5 Hz), 4.20 (d, 1H, CHtBu, J = 9.7 Hz), 3.96–
3.86 (m, 1H, CHCH2OH), 3.34 (dt, 1H, CH2OH,
J = 10.5, 5.3 Hz), 3.26 (dt, 1H, CH2OH, J = 10.5,
6.0 Hz), 2.87 (dd, 1H, CH2Ph, J = 13.7, 5.3 Hz), 2.57
(dd, 1H, CH2Ph, J = 13.7, 8.6 Hz), 1.85 (s, 3H, CH3CO),
0.86 (s, 9H, tBu); 13C NMR (DMSO-d6): δ 169.7 (C),
168.9 (C), 139.1 (C), 129.1 (2CH), 128.0 (2CH), 125.8
(CH), 62.6 (CH2), 59.7 (CH), 52.2 (CH), 36.4 (CH2),
33.9 (C), 26.7 (3CH3), 22.5 (CH3). Anal. Calcd for
(2R)-2-(Acetylamino)-N-[(1S)-1-(hydroxymethyl)-2-
methylpropyl]-3-methylbutanamide (5e).
Recrystallized
from acetonitrile as colorless crystals, yield 6.78 g (73%),
mp 220–225°C; [α]2D0 = +6.5 (c = 0.3 in MeOH); IR
C17H26N2O3: C, 66.64; H 8.55. Found: C, 66.50; H, 8.58.
(2S)-2-(Acetylamino)-N-[(1S)-1-(hydroxymethyl)-2-
1
(KBr): 3380, 3288, 1627, 1566, 1549 cmÀ1; H NMR
methylpropyl]-3,3-dimethylbutanamide (5b). Recrystallized
(DMSO-d6): δ 7.85–7.77 (d, 1H, NH, J = 8.9 Hz), 7.63
(d, 1H, NH, J = 8.9 Hz), 4.50 (app. t, 1H, OH,
J = 5.4 Hz), 4.22 (dd, 1H, CHNHAc, J = 8.9, 6.6 Hz),
3.60–3.53 (m, 1H, CHCH2OH), 3.37–3.34 (m, 2H,
CH2OH), 1.97–1.88 (m, 1H, CHMe2), 1.86 (s, 3H,
CH3CO), 1.85–1.78 (m, 1H, CHMe2), 0.85–0.80 (m,
12H, 2CHMe2); 13C NMR (DMSO-d6): δ 171.0 (C),
from acetonitrile as colorless crystals, yield 7.00 g (71%),
mp 176–179°C; [α]2D0 = À48.8 (c = 0.9 in MeOH); IR
(KBr): 3380, 3287, 1632, 1564, 1544 cmÀ1 1H NMR
;
(DMSO-d6): δ 7.77 (d, 1H, NHAc, J = 9.5 Hz), 7.54 (d,
1H, NH, J = 9.0 Hz), 4.46 (app. t, 1H, OH, J = 5.3 Hz),
4.27 (d, 1H, CHNHAc, J = 9.5 Hz), 3.62–3.57 (m, 1H,
Journal of Heterocyclic Chemistry
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Scalable Synthesis of N-Acetylated α-Amino Acid-Derived Oxazoline Ligands
169.2 (C), 61.2 (CH2), 57.8 (CH), 55.6 (CH), 30.8 (CH),
27.9 (CH), 22.5 (CH3), 19.7 (CH3), 19.4 (CH3), 18.1
(CH3), 18.0 (CH3). Anal. Calcd for C12H24N2O3: C,
58.99; H 9.90. Found: C, 58.92; H, 9.88.
8.3 Hz), 3.92 (dd, 1H, CH2O, J = 8.3, 7.3 Hz), 2.83 (dd,
1H, CH2Ph, J = 13.6, 6.4 Hz), 2.66 (dd, 1H, CH2Ph,
J = 13.6, 7.2 Hz), 1.98–1.89 (m, 1H, CHMe2), 1.87 (s,
3H, CH3CO), 0.85 (d, 3H, CHMe2, J = 6.8 Hz), 0.84 (d,
3H, CHMe2, J = 6.8 Hz); 13C NMR (DMSO-d6): δ 169.1
(C), 165.5 (C), 138.2 (C), 129.3 (2CH), 128.2 (2CH),
126.1 (CH), 71.3 (CH2), 66.5 (CH), 52.0 (CH), 41.2
(CH2), 30.5 (CH), 22.4 (CH3), 19.1 (CH3), 18.3 (CH3).
Anal. Calcd for C16H22N2O2: C, 70.04; H, 8.08. Found:
General procedure for oxazolines 1a–e. Triethylamine
(13.9 mL, 100 mmol) and p-(dimethylamino) pyridine
(245 mg, 2.0 mmol) were added to a stirred suspension
(or solution) of compound 5 (22.0 mmol) in THF
(150 mL). The mixture was cold in an ice bath, and
methanesulfonyl chloride (3.44 g, 30.0 mmol) in 10 mL
of THF was added dropwise. The cooling bath was
removed, and the mixture was allowed to stir at room
temperature (in the case of starting materials 5b,d,e) or at
45°C (in the case of starting materials 5a,c) for 24 h. The
progress of the reaction was monitored by TLC (eluent
CH2Cl2–MeOH, 15:1, two runs). Once the reaction was
completed, the solvent was evaporated in vacuo, and
saturated solution of NH4Cl4 (150 mL) was added to the
residue. The product was extracted with ethyl acetate
(5 × 100 mL); combined organic phases were washed
with 50% K2CO3 solution, dried over Na2SO4. The
solvent was evaporated in vacuo to give products 1,
which were purified as indicated in the following.
C, 70.15; H, 8.10.
N-{(1S)-2-Methyl-1-[(4S)-4-(1-methylethyl)-4,5-dihydro-1,3-
oxazol-2-yl]propyl}acetamide (1d).
Purified by column
chromatography with a mixture of CH2Cl2 and MeOH
(50:1–20:1) as eluent, yield: 4.55 g (91%), viscous liquid;
[α]2D0 = À87.5 (c = 1.3 in MeOH); IR (KBr): 3365, 3222,
1653, 1550 cmÀ1 1H NMR (DMSO-d6): δ 8.06 (d,
;
J = 9.1 Hz, 1H, NH), 4.37–4.28 (m, 1H, CHNH), 4.22
(app. t, 1H, CH2O, J = 9.0 Hz), 3.93 (app. t, 1H, CH2O,
J = 8.3 Hz), 3.85–3.78 (m, 1H, CH-N=C), 1.97–1.92 (m,
CHMe2), 1.85 (s, 3H, CH3CO), 1.63–1.59 (m, 1H,
CHMe2), 0.90–0.83 (m, 9H, 2CHMe2), 0.81 (d,
J = 6.7 Hz, 3H, CHMe2); 13C NMR (DMSO-d6): δ 169.1
(C), 165.1 (C), 71.2 (CH), 69.5 (CH2), 52.1 (CH), 32.1
(CH), 30.5 (CH), 22.4 (CH3), 19.1 (CH3), 18.6 (CH3),
18.3 (CH3), 18.2 (CH3). Anal. Calcd for C12H22N2O2: C,
The yields are given to 22.0 mmol of starting material
5a–e.
N-{(1S)-1-[(4S)-4-Benzyl-4,5-dihydro-1,3-oxazol-2-yl]-2,2-
63.68; H, 9.80. Found: C, 63.50; H, 9.86.
N-{(1R)-2-Methyl-1-[(4S)-4-(1-methylethyl)-4,5-dihydro-1,3-
dimethylpropyl}acetamide (1a). Recrystallized from CCl4
oxazol-2-yl]propyl}acetamide (1e).
Recrystallized from
as colorless crystals, yield 5.58 g (88%), mp 128–130°C;
acetonitrile as colorless crystals, yield 2.59 g (52%),
concentration of the mother liquor gave additionally
0.60 g (12%) of crystals, mp 116–120°C; [α]2D0 = +15.0
(c = 1,0 in MeOH); IR (KBr): 3381, 3234, 3201, 1655,
[α]2D0 = À86.1 (c = 1.2 in MeOH); IR (KBr): 3302, 1659,
1
1608, 1531, 1510 cmÀ1; H NMR (DMSO-d6): δ 8.02 (d,
1H, NH, J = 9.7 Hz), 7.30–7.17 (m, 5H, Ph), 4.40 (d,
1H, CHNH, J = 9.7 Hz), 4.35–4.29 (m, 1H, CH-N=C),
4.18 (dd, 1H, CH2O, J = 8.9, 8.5 Hz), 3.92 (dd, 1H,
CH2O, J = 8.5, 7.2 Hz), 2.84 (dd, 1H, CH2Ph, J = 13.6,
6.4 Hz), 2.67 (dd, 1H, CH2Ph, J = 13.6, 7.3 Hz), 1.90 (s,
3H, CH3CO), 0.92 (s, 9H, tBu); 13C NMR (DMSO-d6): δ
169.0 (C), 165.0 (C), 138.2 (C), 129.3 (2CH), 128.2
(2CH), 126.1 (CH), 70.9 (CH2), 66.5 (CH), 54.7 (CH),
41.2 (CH2), 34.2 (C), 26.6 (3CH3), 22.4 (CH3). Anal.
Calcd for C17H24N2O2: C, 70.80; H, 8.39. Found: C,
70.93; H, 8.38.
1
1552 cmÀ1; H NMR (DMSO-d6): δ 8.05 (d, 1H, NH,
J = 9.4 Hz), 4.35–4.29 (m, 1H, CHNH), 4.23 (dd, 1H,
CH2O, J = 9.2, 8.3 Hz), 3.90 (dd, 1H, CH2O, J = 8.3,
8,0 Hz), 3.87–3.82 (m, 1H, CH-N=C), 1.97–1.92 (m, 1H,
CHMe2), 1.85 (s, 3H, CH3CO), 1.67–1.62 (m, 1H,
CHMe2), 0.88–0.84 (m, 9H, 2CHMe2), 0.82 (d, 3H,
CHMe2, J = 6.8 Hz); 13C NMR (DMSO-d6): δ 169.0 (C),
165.3 (C), 71.2 (CH), 69.3 (CH2), 51.9 (CH), 31.9 (CH),
30.5 (CH), 22.4 (C), 19.1 (CH3), 18.6 (CH3), 18.3 (CH3),
18.1 (CH3). Anal. Calcd for C12H22N2O2: C, 63.68, H,
9.80. Found: C, 63.52; H, 9.80.
N-{(1S)-2,2-Dimethyl-1-[(4S)-4-(1-methylethyl)-4,5-dihydro-
1,3-oxazol-2-yl]propyl}acetamide (1b).
Sublimated in
vacuo, yield 4.44 g (84%), colorless crystals, mp 65–
66°C; [α]2D0 = À120.0 (c = 1.4 in MeOH); IR (KBr):
Acknowledgments. This work was supported by the Belarusian
Republican Foundation for Fundamental Research (Grant No
X17INDG-006) and by The State Committee on Science and
Technology. We also thank Dr. Srimanta Guin (IIT-Bombay)
for useful discussion and inspiration.
1
3315, 3066, 1684, 1566, 1632 cmÀ1; H and 13C NMR
spectra were similar to reported [5].
N-{(1S)-1-[(4S)-4-Benzyl-4,5-dihydro-1,3-oxazol-2-yl]-2-
methylpropyl}acetamide (1c). Recrystallized from CCl4 as
colorless crystals, yield 5.06 g (84%), mp 111–115°C;
[α]2D0 = À86.1 (c = 1.2 in MeOH); IR (KBr): 3315, 1660,
1
1606, 1533 cmÀ1; H NMR (DMSO-d6): δ 8.07 (d, 1H,
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
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