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The Journal of Organic Chemistry
1471 cm-1. 1H NMR (400 MHz, CDCl3) 8.90 (1H, s), 7.49 (1H, d, J = 8.2 Hz), 7.18 (1H, d, J = 8.2 Hz), 4.43 (2H, q, J = 7.2 Hz), 2.45 (3H, s),
1.42 (3H, t, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3) 162.9, 156.2, 154.0, 145.3, 135.9, 133.1 (2C), 118.6, 116.5, 114.9, 62.2, 20.0, 14.2.
HRMS (ESI+/TOF) m/z: [M + Na]+ Calcd for C13H1135ClO4Na 289.0238; Found: 289.0236; Calcd for C13H1137ClO4Na 291.0213; Found:
291.0212.
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5,7-Dichloro-2-oxo-2H-1-benzopyran-3-carboxylic acid, ethyl ester (18e) Following the general procedure for three-component coupling
reaction, the reaction of 2e was carried out. Purification by flash silica gel column chromatography (AcOEt:hexanes = 1:81:0 with 2% CH2Cl2)
afforded the product 18e (35 mg, 61%) as colorless crystals. Mp 72−74 °C (CH2Cl2-hexanes). IR (KBr) 3085, 2984, 1775, 1712, 1594, 1551,
1413 cm-1. 1H NMR (400 MHz, CDCl3) 8.78 (1H, s), 7.39 (1H, d, J = 1.8 Hz), 7.28 (1H, d, J = 1.8 Hz), 4.43 (2H, q, J = 7.2 Hz), 1.41 (3H, t, J =
7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3) 162.5, 155.7, 155.3, 144.0, 140.3, 134.6, 125.9, 118.7, 116.0, 115.2, 62.4, 14.2. HRMS (ESI+/TOF)
m/z: [M + Na]+ Calcd for C12H835Cl2O4Na 308.9692; Found: 308.9715; Calcd for C12H835Cl37ClO4Na 310.9664; Found: 310.9684.
5-Chloro-7-trifluoromethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid, ethyl ester (18f) Following the general procedure for
three-component coupling reaction, the reaction of 2f was carried out. Purification by flash silica gel column chromatography (AcOEt:hexanes =
1:81:0 with 2% CH2Cl2) afforded the product 18f (40mg, 62%) as colorless crystals. Mp 77−79 °C (hexanes). IR (KBr) 3090, 2989, 1777, 1710,
1622, 1564, 1423, 1349 cm-1. 1H NMR (400 MHz, CDCl3) 8.82 (1H, s), 7.61 (1H, d, J = 1.0 Hz), 7.51 (1H, br s), 4.45 (2H, q, J = 7.2 Hz), 1.43
(3H, t, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3) 162.2, 155.4, 154.9, 143.2, 135.5 (q, J = 35 Hz), 135.0, 122.2 (q, J = 275 Hz), 122.0 (q, J
= 4 Hz), 121.2, 119.0, 113.0 (q, J = 4 Hz), 62.6, 14.2. 19F NMR (376 MHz, CDCl3) −63.9 (3F, s). HRMS (ESI+/TOF) m/z: [M + Na]+ Calcd for
C13H835ClF3O4Na 342.9955; Found: 342.9954; Calcd for C13H837ClF3O4Na 344.9930; Found: 344.9929.
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5-Fluoro-8-methoxy-2-oxo-2H-1-benzopyran-3-carboxylic acid, ethyl ester (18h) Following the general procedure for three-component
coupling reaction, the reaction of 2h was carried out. First purification by flash silica gel column chromatography (AcOEt:hexanes = 1:81:0 with
2% CH2Cl2) afforded the isomeric products 18h and 19 (39 mg, 73%) as a mixture of 63:37. The isomers 18h and 19 were separated by second
purification by preparative TLC (CHCl3:Et2O = 15:1, 2-fold development), leading to 18h as pale yellow crystals and 19 as pale yellow crystals.
Mp 125−128 °C (i-Pr2O-CH2Cl2). IR (KBr) 3089, 2981, 1765, 1711, 1624, 1580, 1494, 1442 cm-1. 1H NMR (400 MHz, CDCl3) 8.67 (1H, s),
7.10 (1H, dd, J = 8.7, 4.8 Hz), 6.95 (1H, t, J = 8.7 Hz), 4.40 (2H, q, J = 7.2 Hz), 3.93 (3H, s), 1.39 (3H, t, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3) 162.5, 155.3, 152.5 (d, J = 253 Hz), 144.4 (d, J = 5 Hz), 143.4 (d, J = 4 Hz), 141.8 (d, J = 4 Hz), 118.4, 116.0 (d, J = 9 Hz), 109.4 (d, J
= 21 Hz), 108.7 (d, J = 21 Hz), 62.1 56.7, 14.1. 19F NMR (376 MHz, CDCl3) −128.3 (1F, m). HRMS (ESI+/TOF) m/z: [M + Na]+ Calcd for
C13H11FO5Na 289.0483; Found: 289.0486.
8-Fluoro-5-methoxy-2-oxo-2H-1-benzopyran-3-carboxylic acid, ethyl ester (19) Mp 158−159 °C (hexanes). IR (KBr) 2984, 2950, 1766,
1715, 1618, 1581, 1496, 1461 cm-1. 1H NMR (400 MHz, CDCl3) 8.85 (1H, d, J = 1.4 Hz), 7.34 (1H, t, J = 9.2 Hz), 6.63 (1H, dd, J = 9.2, 3.2
Hz), 4.41 (2H, q, J = 7.2 Hz), 3.95 (3H, s), 1.41 (3H, t, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3) 162.9, 155.3, 152.9 (d, J = 3 Hz), 143.8
(d, J = 2 Hz), 143.6 (d, J = 13 Hz), 143.4 (d, J = 247 Hz), 120.8 (d, J = 18 Hz), 116.8, 109.9, 104.3 (d, J = 6 Hz), 62.0, 56.3, 14.2. 19F NMR (376
MHz, CDCl3) −143.6 (1F, m). HRMS (ESI+/TOF) m/z: [M + Na]+ Calcd for C13H11FO5Na 289.0483; Found: 289.0482.
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