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glassware with a magnetic stirring bar placed inside. Merck silica
gel (230–400 mesh) was used for the flash column chromatography.
Ethyl acetate and hexane mixture was used as an eluent system to
purify all the compounds. Buchi rotary evaporator was used to
concentrate the organic solutions. The yields were calculated from
General Procedure for the Synthesis of
5-Hydroxy-2-Isoxazolines 4 from Oximes 1
Oxime 1 (0.2 mmol, 1.0 equiv), TEMPO (0.3 mmol, 1.5 equiv), and
PhI(OAc)2 (0.2 mmol, 1.0 equiv) in MeCN (6.0 mL) were added to an
oven-dried glass tube equipped with a magnetic stir bar. The
reaction was continued for 24 h under N2 atmosphere. Water was
added, and the mixture was extracted with ethyl acetate (3 times).
The combined organic layer was dried over sodium sulphate. Rotary
evaporator was used to remove the solvent. The crude product was
then purified by flash column chromatography using silica gel
(mesh 230 400). Hexane and ethyl acetate (93:7 to 89:11) as
eluents were used to afford the corresponding 5-hydroxy-2-isoxazo-
line derivatives.
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the products obtained after column purification. H and 13C NMR
spectra were recorded on a 400 MHz Jeol and 500 MHz Bruker.
Proton chemical shifts are reported in ppm downfield from relative
to the residual 1H signal of CDCl3 (δ 7.26ppm) and DMSO-d6
(δ 2.50ppm). Carbon chemical shifts were internally referenced to
the deuterated solvent signals in CDCl3 (δ 77.16ppm) and in DMSO-
d6 (δ 39.52ppm). Coupling constants (J) are measured in hertz (Hz).
General Procedure for the Synthesis of Oximes 1
All oximes were prepared according to the reported literature
procedure.[21] To a solution of ketone (1.0 equiv) in EtOH (0.5 M) was
added hydroxylamine hydrochloride (1.5 equiv) and NaOAc
(2.0 equiv). The reaction mixture was then stirred at room temper-
General Procedure for the Synthesis of Acetyl Protected
Oximes 5 and 6
Oxime (1.0 equiv) and acetyl chloride (1.5 equiv) were dissolved in
dichloromethane, and the mixture was cool with an ice-bath.
Triethylamine (1.5 equiv) was added dropwise. The reaction mixture
was brought to room temperature and stirring was continued for
4 hours. Water was added to the reaction mixture, and the organic
phase was separated. The organic phase was washed with
saturated NH4Cl, aqueous Na2CO3 solution, and brine. The organic
layer was dried over sodium sulphate and evaporated in rotary
evaporator. The residue was purified by column chromatography
using hexane and ethyl acetate (93:7) as eluent.
°
ature or heated at 60 C until the ketone was consumed as
monitored by TLC (TLC Silica gel 60 F254). The solvent was
evaporated, and the residue was diluted with water and ethyl
acetate. The aqueous layer was extracted with ethyl acetate. The
combined organic layers were washed with 1.0 N aqueous HCl and
brine. Organic layer was dried over Na2SO4 and concentrated in a
rotary evaporator. Purification of the crude product by flash column
chromatography using hexane/ethyl acetate as eluent afforded the
corresponding oxime.
General Procedure for the Synthesis of Isoxazolines 2 from
Oximes 1
Acknowledgements
Oxime 1 (0.2 mmol, 1.0 equiv), TEMPO (0.08 mmol, 0.4 equiv),
K2S2O8 (0.6 mmol, 3.0 equiv), and H2O (6.0 mmol, 30 equiv) in MeCN
(6.0 mL) were added to an oven-dried glass tube equipped with a
magnetic stir bar. Next, the tube was placed in a pre-heated oil-
D. S. thanks the IISER Kolkata for startup Grant, SERB for Early
Career Research Award (ECRA) and DST-SERB for Ramanujan
Fellowship. S. M., S. B., and K. G. G. thanks IISER-K, IISER-K, and
DST their PhD fellowship.
°
bath at 50 C. The mixture was stirred at the same temperature for
30 h. Water was added, and the mixture was extracted with ethyl
acetate (3 times). The combined organic layer was dried over
Na2SO4. Solvent was removed in a rotary evaporator. The crude
product was then purified by flash column chromatography on
silica gel (mesh 230 400) using hexane and ethyl acetate (97:3 to
94:6) as eluents to afford the corresponding isoxazoline derivatives.
Conflict of Interest
The authors declare no conflict of interest.
General Procedure for the Synthesis of Isoxazoles 3 from
Oximes 1
Keywords: isoxazolines · isoxazoles · heterocycles · hydrogen
atom transfer (HAT) · divergent synthesis
Oxime 1 (0.2 mmol, 1.0 equiv), TEMPO (0.08 mmol, 0.4 equiv),
oxone (0.6 mmol, 3.0 equiv), and KI (0.02 mmol, 0.1 equiv) in MeCN
(2.0 mL) were added to an oven-dried glass tube equipped with
a magnetic stir bar. The tube was placed in a pre-heated oil-bath at
°
50 C. The mixture was stirred at the same temperature for 48 h.
[3] E. M. Dauncey, S. P. Morcillo, J. J. Douglas, N. S. Sheikh, D. Leonori,
Water was added, and the mixture was extracted with ethyl acetate
(3 times). The combined organic layer was dried over sodium
sulphate. The solvent was removed in a rotary evaporator. The
crude product was purified by flash column chromatography using
silica gel (mesh 230 400). Hexane and ethyl acetate (98:2 to 94:6)
as eluents were used to afford the corresponding isoxazole
derivatives.
[7] a) R. D. Sun, R. B. Lee, R. P. Tangallapally, R. E. Lee, Eur. J. Med. Chem.
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