E. Pǎunescu et al. / Dyes and Pigments 91 (2011) 427e434
429
recovered by filtration, and washed sequentially with MeOH, Et2O,
CH2Cl2 and acetone. The precipitate thus obtained represents a first
crop of the desired product (3.02 g) which could be further used
without any other purification. The washing organic filtrate was
also concentrated and further submitted to successive recrystalli-
zation (in mixtures of Et2O, CH2Cl2 and acetone) and flash column
chromatography (cyclohexaneeEtOAc with a step gradient from
7:3 to 4:6) but the desired coumarin could not be separated from
the dimeric structure also formed in the reaction (vide infra). The
expected product was thus obtained as pale yellow solid (3.02 g,
yield 39%). Rf (cyclohexaneeEtOAc, 5:5, v/v) ¼ 0.3; 1H NMR
2CHcoum a Cl), 6.86 (2H, s, 2CHcoum b Cl), 3.33 (2H, d, 2(0.5CH2CO),
J ¼ 15.5 Hz), 3.09 (2H, d, 2(0.5CH2CO), J ¼ 15.5 Hz). 13C NMR
(75.5 MHz, acetone-d6):
d
¼ 166.0 (2C), 155.0 (2C), 151.5 (2C), 127.5
(2C), 118.4 (2C), 117.5 (2C), 106.4 (2C), 40.55 (2C), 39.1 (1C, C-4); MS
(ESI, negative mode): m/z 379.13 and 381.13 [M ꢂ H]ꢂ, 758.73 and
762.63 [2M ꢂ H]ꢂ, calcd mass for C17H10Cl2O6 381.17.
2.2.6. Methyl 2-(8-fluoro-2-oxo-7-(trifluoromethylsulfonyloxy)-
2H-chromen-4-yl)acetate (17)
To a suspension of phenol 13 (2.2 g, 8.7 mmol, 1 equiv) and N-
phenyl-bis(trifluoromethanesulfonimide) (3.43 g, 9.6 mmol, 1.1
equiv) in dry CH3CN (100 mL), was added DIEA (2.05 mL,
12.2 mmol, 1.4 equiv) and the resulting yellow solution was stirred
at rt overnight. The reaction was checked for completion by TLC
(cyclohexaneeEtOAc, 6:4, v/v). Thereafter, the reaction mixture was
concentrated and the obtained crude was dissolved in EtOAc
(200 mL) and washed with deionized water (200 mL) and brine
(150 mL). The organic layer was dried over anhydrous Na2SO4 and
evaporated to dryness. The crude product was purified by flash
column chromatography (cyclohexaneeEtOAc with a step gradient
from 7:3 to 6:4, v/v) to give the desired product as a pale yellow
solid (3.24 g, yield 97%). Rf (cyclohexaneeEtOAc, 6:4, v/v) ¼ 0.3; 1H
(300 MHz, acetone-d6):
d
¼ 9.50e10.10 (1H, s br, OH), 7.39 (1H, dd,
CHcoum g F, J ¼ 1.9 and 8.9 Hz), 7.00 (1H, dd, CHcoum b F, J ¼ 8.9 and
7.9 Hz), 6.31 (1H, s, CHcoumCO), 3.94 (2H, s, ArcoumCH2CO), 3.69 (3H,
s, OCH3); 13C NMR (75 MHz, acetone-d6):
d
¼ 170.1, 159.6, 150.0,
149.0 (d, J ¼ 10 Hz), 144.4 (d, J ¼ 9 Hz), 139.6 (d, J ¼ 244 Hz), 121.2
(d, J ¼ 4 Hz), 114.3, 114.2, 113.8, 52.7, 37.9; 19F NMR (282.5 MHz,
acetone-d6):
d
¼ 17.02; MS (ESI, negative mode): m/z 251.40
[M ꢂ H]ꢂ, calcd mass for C12H9FO5 252.20; elemental analysis (%)
calcd: C, 57.15; H, 3.60; found: C, 58.36; H, 4.10.
2.2.3. Side product e dimeric structure (15)
Pale green solid. Rf (cyclohexaneeEtOAc, 5:5, v/v) ¼ 0.4; 1H NMR
NMR (300 MHz, CDCl3):
2.1 Hz), 7.29 (1H, dd, CHcoum
CHcoumCO), 3.81 (2H, s, CH2CO), 3.76 (3H, s, OCH3); 13C NMR
(75.5 MHz, CDCl3):
d
¼ 7.46 (1H, dd, CHcoum
g
F, J ¼ 9.1 and
(300 MHz, acetone-d6):
d
¼ 9.10e9.60 (2H, s br, 2OH), 6.82 (2H, dd
b
F, J ¼ 9.1 and 6.2 Hz), 6.50 (1H, s,
overlayed, 2CHcoum b F, J ¼ 8.3 and 8.3 Hz), 6.71 (2H, dd, CHcoum g F,
J ¼ 1.3 and 8.3 Hz), 3.38 (2H, d, 2(0.5CH2CO), J ¼ 15.5 Hz), 3.14 (2H,
d, 2(0.5CH2CO), J ¼ 15.5 Hz); 13C NMR (75.5 MHz, acetone-d6):
d
¼ 168.5, 157.6, 147.0 (d, J ¼ 2 Hz), 143.3 (d,
J ¼ 9 Hz), 142.1 (d, J ¼ 258 Hz), 138.5 (d, J ¼ 11 Hz), 120.8 (1C, C-9),
d
¼ 165.4 (2C), 147.0 (2C, d, J ¼ 10 Hz), 141.2 (2C, d, J ¼ 9 Hz), 140.7
120.0 (d, J ¼ 5 Hz), 118.8, 118.7 (d, J ¼ 319 Hz), 118.2, 53.1, 38.0; 19F
(2C, d, J ¼ 245 Hz),120.9 (2C, d, J ¼ 4 Hz),118.7 (2C, d, J ¼ 1 Hz),114.0
NMR (282.5 MHz, CDCl3):
d
¼
ꢂ72.93 (3F, d, CF3,
(2C, d, J ¼ 2 Hz), 40.6 (2C), 30.6. 19F NMR (282.5 MHz, acetone-d6):
J ¼ 5.2 Hz), ꢂ144.56 (1F, qv, F, J ¼ 5.2 Hz); MS (ESI, negative mode):
m/z 383.00 and 385.07 [M ꢂ H]ꢂ, calcd mass for C13H8F4O7S 384.26;
elemental analysis (%) calcd: C, 40.64; H, 2.10; S, 8.34; found: C,
40.75; H, 2.29; S, 8.50.
d
¼ 20.11; MS (ESI, negative mode): m/z 347.13 [M ꢂ H]ꢂ, 694.80
[2M ꢂ H]ꢂ, calcd mass for C17H10F2O6 348.26.
2.2.4. Methyl 2-(6-chloro-7-hydroxy-2-oxo-2H-chromen-4-yl)
acetate (14)
2.2.7. Methyl 2-(6-chloro-2-oxo-7-(trifluoromethylsulfonyloxy)-
2H-chromen-4-yl)acetate (18)
To a solution of 4-chlororesorcinol (4.0 g, 27.7 mmol, 1 equiv) in
methanesulfonic acid (56 mL) at 0 ꢀC was added dropwise dimethyl
1,3-acetonedicarboxylate (4.8 mL, 33.2 mmol, 1.2 equiv) over 30 min
under vigorous stirring. The resulting brown viscous solution was
kept at 0 ꢀC for further 30 min then allowed warm up at rt and
stirred for further 5 days. The reaction was checked for completion
by TLC (cyclohexaneeEtOAc, 5:5, v/v). Thereafter, the reaction
mixture was added dropwise under vigorous stirring to pre-cooled
deionized water and then stirred for further 30 min at rt. The
precipitating product (as a yellow-beige bulky solid) was then
recovered by filtration, and washed sequentially with MeOH, Et2O,
CH2Cl2 and acetone. The precipitate thus obtained represents a first
crop of the desired product (1.53 g). The washing organic filtrate was
also concentrated and further submitted to successive recrystalli-
zations (in mixtures of Et2O, CH2Cl2 and acetone) and flash column
chromatography (cyclohexaneeEtOAc with a step gradient from 7:3
to 4:6, v/v) to recover a second crop of pure desired product (1.54 g).
The expected product was thus obtained as a pale pink solid (3.07 g,
11.44 mmol, yield 41%). Rf (cyclohexaneeEtOAc, 5:5, v/v) ¼ 0.5; Rf
(CH2Cl2eEt2O, 5:0.5, v/v) ¼ 0.3; 1H NMR (300 MHz, acetone-d6):
To a suspension of phenol 14 (0.23 g, 0.86 mmol, 1 equiv) and N-
phenyl-bis(trifluoromethanesulfonimide) (0.34 g, 0.95 mmol, 1.1
equiv) in dry CH3CN (20 mL), was added DIEA (0.2 mL, 1.21 mmol,
1.4 equiv) and the resulting yellow solution was stirred at rt over-
night. The reaction was checked for completion by TLC (cyclo-
hexaneeEtOAc, 6:4, v/v). Thereafter, the reaction mixture was
concentrated and the resulting residue was dissolved in EtOAc
(100 mL) and washed with deionized water (100 mL) and brine
(100 mL). The organic layer was dried over anhydrous Na2SO4 and
evaporated to dryness. The crude product was purified by flash
column chromatography (cyclohexaneeEtOAc with a step gradient
from 7:3 to 6:4, v/v) to give the desired product as a white solid
(0.36 g, yield 94%). Rf (cyclohexaneeEtOAc, 7:3, v/v) ¼ 0.3; 1H NMR
(300 MHz, CDCl3):
d
¼ 7.70 (1H, s, CHcoum a Cl), 7.33 (1H, s, CHcoum
b
Cl), 6.46 (1H, s, CHcoumCO), 3.74 (5H, s, CH2, CH3); 13C NMR (CDCl3,
75.5 MHz):
d
¼ 168.6, 158.9, 152.4, 146.9, 146.4, 134.3, 126.8, 119.8,
119.0, 118.6 (d, J ¼ 319 Hz), 112.4, 53.1, 37.7; 19F NMR (282.5 MHz,
CDCl3):
d
¼ ꢂ73.09 (3F, CF3); MS (ESI, negative mode): m/z 399.12
and 403.11 [M ꢂ H]ꢂ, calcd mass for C13H8ClF3O7S 400.71;
elemental analysis (%) calcd: C, 38.97; H, 2.01; S, 8.00; found: C,
39.16; H, 2.24; S, 8.11.
d
¼ 7.54 (1H, s, CHcoum
CHcoumCO), 3.97 (2H, s, CH2), 3.71 (3H, s, CH3); 13C NMR (75.5 MHz,
acetone-d6):
a Cl), 6.95 (1H, s, CHcoum g Cl), 6.30 (1H, s,
d
¼ 170.1, 160.3, 157.0, 154.8, 149.2, 127.1, 118.2, 114.9,
113.7, 104.7, 52.7, 37.7; MS (ESI, negative mode): m/z 267.46 and
269.39 [M ꢂ H]ꢂ, calcd mass for C12H9ClO5 268.66; elemental
analysis (%) calcd: C, 53.65; H, 3.38; found: C, 53.89; H, 3.39.
2.3. Paladium-catalyzed amination reactions
2.3.1. Methyl 2-(7-amino-8-fluoro-2-oxo-2H-chromen-
4-yl)acetate (5)
2.2.5. Side-product e dimeric structure (16)
Previous to use, DME was degassed for at least 30 min under an
argon flow. To a suspension of Pd2(dba)3 (48 mg, 0.052 mmol, 0.1
equiv) and Xantphos (60 mg, 0.104 mmol, 0.2 equiv) in DME (5 mL)
Pale orange solid; Rf (CH2Cl2eEt2O, 5:0.5, v/v) ¼ 0.5; 1H NMR
(300 MHz, acetone-d6):
d
¼ 9.90e10.10 (2H, s br, 2OH), 7.01 (2H, s,