d, Jcp = 30.7 Hz, CO). 3-Chloro-3-fluoro-2,4-pentanedione (5c) was prepared starting from 4c; reaction time 2 h; eluting system for flash chromatography n-hexane/CHzClz, 8515; yield 95%, 'H NMR 6 2.48 (d, J = 2.7 Hz); ' BF NMR 6 -126.2 (septet, CF), 197.48 (d, Jcs = 27.0 Hz, CO); IR (film) 2925,1738 (CO) cm-'; MS (CI) m / e 153 and 155 (M+ + 1). 1,3-Dimethyl-5,5-difluorobarbituric acid (5e) was prepared starting from 1,3-dimethylbarbituric acid (4e) and 2.2 equiv of 1; acetonitrile was used as reaction solvent; reaction time 6 h; eluting system for flash chromatography n-hexanelethyl acetate 7:3; yield 95%; mp 9); 'gF NMR 6 -122.8 (d, J 20.36 (CH,), 25.00 (CH,), 64.40 (CHzO), 102.14 (d, J c 2.5 Hz); 'Bc NMR 6 13.83 (CH,), 251.8 J 2.7 Hz); '9C NMR 6 24.95 (CH,), 102.84 (d, Jcp 269.6 Hz, 125-127 "C; 'H NMR 6 3.40 (a); 'H NMR (CDSCN) 6 3.26 (t, J = 0.5 Hz); ' BF NMR 6 -108.7; '9C NMR (CDSCN) 6 29.64 (CH,), 99.61 (t, J c s = 245.5 Hz, CFZ), 150.35 (NCON), 160.97 (t, J c r = 27.8 Hz, COCFJ; IR (Nujol) 1687 (CO), 1448,1304 cm-' ; MS (EI) m / e 192 (M+), 176,135, 107,78.Ethyl 3-fluoro-3-methyl-2-oxobutanoate (7a) was prepared starting from 6a; reaction time 27 h; eluting system for flash chromatography n-hexanelethyl ether, 64; yield 95%; 'H NMR 6 1.39 (3 H, t), 1.64 (6 H, d, J = 21.6 Hz), 4.41 (2 H, 9); '9 NMR 6 -151.4 (septet, J = 21.3 Hz) ('9 NMR 6 -152.0 (septet, J = 21.3 Hz, ref 13)); '9c NMR 6 13.87 (CHJ, 24.14 (d, Jcp = 24.1 Hz, CHJ, 64.00 (CHZO), 97.85 (d, Jcp = 177.9 Hz, CF), 164.08 (COO), 196.82 (d, Jcr = 35.3 Hz, CO), MS (CI) m / e 163 (M+ + l), 143. 3-Fluoro-3-methyl-2-oxopentanoic acid (7b) was prepared starting from 6 b CHCl, saturated with H80, was used 88 reaction solvent; reaction time 24 h; eluting system for flash chromatography CHzClz/ethyl acetate/acetic acid, 5&50:0.5; yield 95%; ' H NMR 6 0.98 (3 H, t), 1.65 (3 H, d, J = 21.8 Hz), 1.9-2.2 (2 H, m); ' BF NMR 6 -160.1 (sextet, J = 21.5 Hz); '9C NMR 6 7.05 (CHJ, CO); I$ ( f i l m ) 3300-2500 (COOH), 1748,1193 cm-'; MS (E11 m / e 148 (M+), 128,121,75. 3-Fluoro-2-oxobutanoic acid (7c) was prepared starting from 6c; reaction time 18 h; eluting system for flash chromatography CHzClz/ethyl acetate/acetic acid, 5Of&O.:o.5; yield 95%; lH NMR (DzO) 6 1.36 (3 H, dd, J = 6.3,25.5 Hz, CHJ, 21.86 (d, J c r = 23.2 Hz, CHJ, 30.39 (d, Jcp = 22.5 Hz, CHJ, 99-95 (d, J c = 182.0 Hz, CF), 163.5 (COOH), 195.5 (d, Jcp = 32.9 Hz, 4.86 (1 H, dq, J = 6.3,46.7 Hz, CHF); ' BF NMR (DzO) b -186.2 (dq, J = 25.6, 47.6 Hz); "C NMR (DzO) 6 12.74 (d, Jcp = 21.6 Hz, CHd, 90.97 (d, J c = 172.7 Hz, CF), 92.90 (d, Jcp = 23.4 Hz, OCO of the hydratetketone), 171.92 (COOH).A efficient process for the commercial preparation of the therapeutically important cholesterol lowering drug synvinolin (2: simvastatin, ZOCOR) from mevinolin (1: lovastatin, MEVACOR) is reported. The synthesis reliea upon deactivation of the &lactone carbonyl toward enolization via conversion to the bis[(tert-butyldimenyl)o~] butylamide 7. An extremely high conversion (99.7%) ester enolate alkylation of 7 affords 8 an...
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