Chemistry of Heterocyclic Compounds 2021, 57(3), 253–260
+
3
stirring at 80°С for 10 h. Then, the reaction mixture was
concentrated under reduced pressure until the formation of
a solid residue which was dried in an oil pump vacuum
(10–3 mmHg). Yield 94 mg (91%), hygroscopic beige solid,
5-СН2); 3.80 (2Н, br. s, NH2 ); 4.03 (1Н, qdd, JHF = 9.5,
3J = 4.0, 3J = 3.6, 3-CH); 4.59 (1Н, ddd, 3J = 8.3, 3J = 4.0,
3J = 3.7, 4-CH); 4.77 (1Н, d, J = 3.6, 2-CH). 13C NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 38.8 (SO2СН3); 45.5
3
1
2
mp >190°С (decomp.). H NMR spectrum (DMSO-d6),
(C-5); 45.7 (q, JCF = 30.3, C-4); 58.9 (CH); 59.7 (CH);
δ, ppm: 3.21 (3Н, s, CH3); 3.64 (1H, br. s, NH); 7.55–7.56
(1Н, m, CH); 13.29 (1Н, br. s, СО2Н). 13C NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 44.4 (CH3); 112.6 (q,
2JCF = 38.1, C-3); 121.7 (q, JCF = 267.8, CF3); 124.6 (q,
3JCF = 1.6); 125.7 (q, 3JCF = 3.5); 127.2 (C-2); 159.5 (С=О).
19F NMR spectrum (DMSO-d6), δ, ppm: –51.6 (3F, s, CF3).
Mass spectrum (LC/MS), m/z: 258 [M+H]+. Found, %:
C 49.92; H 3.52; N 4.84; S 11.04. C7H6F3NO4S.
Calculated, %: C 49.82; H 3.48; N 4.84; S 11.08.
125.2 (q, JCF = 280.2, CF3); 166.9 (C=O). 19F NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): –69.1 (3F, d, 2JFН = 9.5,
CF3). Mass spectrum (LC/MS), m/z: 262 [M-HCl+H]+. Found,
%: C 28.21; H 3.76; N 4.82; S 10.70. C7H11ClF3NO4S.
Calculated, %: C 28.24; H 3.72; N 4.71; S 10.77.
X-ray structural analysis of compound 3b was
performed on a Bruker SMART APEX II diffractometer.
Crystals of compound 3b were obtained from MTBE
solution. The results were solved by the direct method and
refined by the least-squares technique using the Bruker
SHELXTL software package.18 The full set of X-ray
structural data was deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 2018284).
Ethyl 4-methanesulfonyl-3-(trifluoromethyl)-2-carboxy-
late (11). A solution of glacial AcOH (66 mg, 1.10 mmol)
in MeOH (2 ml), followed by NaBH3CN (75.6 mg,
1.20 mmol) was added with stirring at 0°С to a solution of
pyrroline 3b (287 mg, 1.00 mmol) in anhydrous MeOH
(8 ml). The reaction mixture was stirred at room
temperature for 12 h. Then, the solvent was evaporated
under reduced pressure and the residue was treated with
EtOAc (10 ml). The insoluble precipitate was filtered off,
the filtrate was washed with saturated aqueous NaHCO3
(2×2 ml), dried over Na2SO4, and the solvent was
evaporated to dryness to afford an analytically pure
compound. Yield 0.24 g (83%), yellowish transparent
References
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1
viscous oil. H NMR spectrum (CDCl3), δ, ppm (J, Hz):
1.30 (3H, t, 3J = 7.1, OСН2CH3); 2.63 (1Н, br. s, NH); 2.97
3
3
(3H, s, SO2CH3); 3.35 (1Н, qdd, JHF = 9.1, J = 5.1,
3J
=
3.8, 3-CH); 3.34 (1Н, dd, АВ system,
3
J = 12.5, J = 7.4, 5-СН2) and 3.72 (1Н, dd, АВ system,
J = 12.5, 3J = 3.8, 5-СН2); 3.62 (1Н, ddd, 3J = 7.4, 3J = 3.8,
3J = 3.8, 4-CH); 3.97 (1Н, d, J = 5.1, 2-CH); 4.22–4.30
3
(2Н, m, OСН2CH3). 13C NMR spectrum (CDCl3), δ, ppm
(J, Hz): 14.1 (OСН2CH3); 39.8 (SO2СН3); 49.1 (q,
2JCF = 27.4, C-3); 49.4 (C-5); 62.3 (q, 3JCF = 1.7, CH); 62.5
(OСН2CH3); 63.7 (CH); 126.0 (q, JCF = 277.3, CF3); 170.2
(C=O). 19F NMR spectrum (CDCl3), δ, ppm (J, Hz): –70.2
(3F, d, JFН = 9.1, CF3). Mass spectrum, m/z: 290 [M+H]+.
2
Found, %: C 37.44; H 4.86; N 4.90; S 11.00. C9H14F3NO4S.
Calculated, %: C 37.37; H 4.88; N 4.84; S 11.08.
4-Methanesulfonyl-3-(trifluoromethyl)pyrrolidine-
2-carboxylic acid hydrochloride (12). HCl, 20% solution
in 1,4-dioxane (1 ml) was added with stirring to a solution
of ester 11 (173 mg, 0.60 mmol) in 1,4-dioxane (2 ml).
After some time, a white precipitate of hydrochloride of
ester 11·HCl precipitated. The suspension was stirred for
30 min, the precipitate was filtered off, dissolved in 9 M
aqueous HCl (3 ml), and the resulting mixture was heated
with stirring at 80°С for 10 h. The reaction mixture was
concentrated under reduced pressure until the formation of
a solid residue which was dried in an oil pump vacuum
(10–3 mmHg). The dried residue was treated with Et2O (5 ml),
and the precipitate that separated was filtered off and dried.
Yield 0.17 g (95%), beige solid, mp > 235°С (decomp.).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 3.28 (3H,
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Chem. Commun. 2012, 48, 4067.
3
s, SO2CH3); 3.68 (1Н, dd, АВ system, J = 13.7, J = 8.3,
3
5-СН2) and 3.82 (1Н, dd, АВ system, J = 13.7, J = 3.7,
259