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Baranovsky et al.
1H NMR (acetone-d6): ꢀ 1.14 (6H, m, CH3CH2), 1.43 (6H, m, CH3CH),
2.59 (2H, t, J ¼ 7.6 Hz, H-2), 2.84 (2H, t, J ¼ 7.6 Hz, H-3), 3.56 (2H, m,
CH3CH2), 3.61 (3H, s, OCH3), 3.81 (2H, m, CH3CH2), 5.34 (1H, q,
J ¼ 5.3 Hz, CH3CH), 5.39 (1H, dq, J ¼ 5.3, 2.1 Hz, CH3CH), 6.81 (1H,
dd, J ¼ 2.1, 8.2 Hz, H-60), 6.70 (1H, d, J ¼ 2.0 Hz, H-20), 6.70 (1H, d,
J ¼ 8.2 Hz, H-50); 13C NMR (acetone-d6) ꢀ 15.55/15.56 (CH3CH2),
20.86/20.89/20.90/20.93 (CH3-CH), 30.94 (C-3), 36.17 (C-2), 51.56
(OCH3), 62.37/62.40/62.47/62.52 (CH3CH2), 101.61/101.69/101.69/
101.76 (CH3-CH), 120.44/120.46 and 120.53/120.58 (C-20 and C-50),
123.10/123.14 (C-60), 136.28/136.33 (C-10), 147.15/147.23 (C-40),
148.82/148.88 (C-30), 173.35 (C-1); EIMS: m/z 324 (Mþ, 10), 252 (65),
180 (90), 123 (70); EIMS: m/z 340 (Mþ, 10), 268 (30), 196 (95), 123 (45);
HRMS: Calcd. for C18H28O6: 340.1886, Found: 340.1885.
4.4.3. 4-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-2-
Ketobutylphosphonic acid dimethyl ester (33)
To a stirred solution of dimethyl methylphosphonate (2.03 mL,
19 mmol) in THF (30 mL) at ꢁ78ꢀC was added a 1.6 N solution of
MeLi in ether (11.6 mL, 18.6 mmol) via a syringe. The resulting solution
was stirred for 1 h at the indicated temperature and ester 32 (2.36 g,
6.5 mmol) in THF (15 mL) was added dropwise at ꢁ78ꢀC. After this
addition the cooling bath was removed and the reaction was allowed to
warm slowly to room temperature. The reaction was stirred at room
temperature for 3 h, quenched with saturated NH4Cl, and extracted
with EtOAc. The organic phase was washed with brine, dried, and evap-
orated to give an oily material (2.9 g). The product was separated via a
silica gel column with CHCl3 as eluent to give the starting material
(0.23 g, 11%) followed by phosphonate 33 as pale yellow oil (2.45 g,
87%). IR (neat): (ꢁmax cmꢁ1) 2981, 1718, 1600, 1507, 1260, 1034, 948;
1H NMR (acetone-d6): ꢀ 1.14 (6H, m, CH3CH2), 1.42 (6H, m, CH3CH),
2.79 (2H, t, J ¼ 7.4 Hz, H-4), 2.96 (2H, t, J ¼ 7.4 Hz, H-3), 3.18 (2H, d,
2JH-P ¼ 22.5 Hz, H-1), 3.55 (2H, m, CH3CH2), 3.69 (3H, s, OCH3), 3.71
(3H, s, OCH3), 3.80 (2H, m, CH3CH2), 5.33 (1H, q, J ¼ 5.4 Hz, CH3CH),
5.39 (1H, dq, J ¼ 1.4, 5.4 Hz, CH3CH), 6.81 (1H, dd, J ¼ 1.9, 8.0 Hz, H-
60), 6.98 (1H, d, J ¼ 1.9 Hz, H-20), 6.99 (1H, d, J ¼ 8.0 Hz, H-50);
13C NMR (acetone-d6): ꢀ 15.57/15.59 (CH3CH2), 20.88/20.92/20.96/
1
20.99 (CH3CH), 29.48 (C-4), 41.58 (d, JC-P ¼ 126.5 Hz, C-1), 45.89/
45.90 (C-3), 53.04 (OCH3), 53.09 (OCH3), 62.42/62.45/62.55/62.59
(CH3CH2), 101.66/101.73/101.76/101.83 (CH3CH), 120.46/120.52
and 120.56/120.64 (C-20 and C-50), 123.15/123.19 (C-60), 136.62/136.73