G. Alluraiah et al.
anhydrous THF at 0 °C, 39 cm3 n-BuLi (2.0 M in n-
hexane, 74.56 mmol, 4.0 eq) was added and reaction
mixture stirred for 30 min at the same temperature, after
that reaction mixture taken to -78 °C and 6.5 g EtOAc
(74.56 mmol, 4.0 eq) was added in one pot by syringing.
Stirring was continued at -78 °C for 1 h, and then 4.4 g
aldehyde (18.64 mmol, 1.0 eq) dissolved in 25 cm3 dry
THF was added to above reaction mixture at -78 °C and
reaction mixture stirred at the same temperature for 1 h.
The reaction mixture was quenched with 50 cm3 sat. aq.
NH4Cl solution at 0 °C, extracted with EtOAc
(2 9 100 cm3), washed with 50 cm3 water, 50 cm3 brine,
concentrated the organic layer, and purified by column
chromatography (silica gel, 60–120 mesh, 12 % EtOAc in
[a]D = -114.3 (c = 1.1, CHCl3); 1H NMR (CDCl3,
300 MHz): d = 7.20 (d, 2H, J = 8.6 Hz, ArH-PMB),
6.79 (d, 2H, J = 8.6 Hz, ArH-PMB), 4.47 (d, 1H,
J = 11.1 Hz, benzylic), 4.36 (d, 1H, J = 11.1 Hz, ben-
zylic), 4.14 (q, 2H, J = 7.0 Hz, –OCH2), 3.74 (s, 3H, –
OCH3), 3.63 (m, 1H, –OCH), 3.39 (m, 1H, –OCH), 2.71
(dd, 1H, J = 8.0, 15.3 Hz, –CH), 2.50 (dd, 1H, J = 5.2,
15.3 Hz, –CH), 1.58–1.29 (m, 6H, 3 CH2), 1.27 (t, 3H,
J = 7.1 Hz, –OCH2CH3) 1.11 (d, 3H, J = 6.1 Hz, –CH3)
ppm; 13C NMR (100 MHz, CDCl3): d = 171.3, 159.3,
141.2, 130.1, 129.8, 114.3, 75.6, 72.2, 66.8, 59.8, 56.1,
42.4, 37.3, 34.7, 26.0, 23.2, 20.9, 14.7 ppm; IR (neat):
V = 3354, 2928, 2862, 2105, 1613, 1514 cm-1; ESI–MS:
ꢀ
m/z = 347 [(M ? Na)?].
1
pet. ether) to afford 4 (2.17 g) in 72 % yield. H NMR
(3S,7R)-Ethyl 3-(benzyloxy)-7-(4-methoxybenzyloxy)
octanoate (10, C25H34O5)
(300 MHz, CDCl3): d = 7.21 (d, 2H, J = 8.8 Hz, ArH-
PMB), 6.81 (d, 2H, J = 8.8 Hz, ArH-PMB), 4.44 (d, 1H,
J = 11.1 Hz, benzylic), 4.38 (d, 1H, J = 11.1 Hz, ben-
zylic), 4.14 (q, 2H, J = 7.0 Hz, –OCH2), 3.74 (s, 3H, –
OCH3), 3.66 (m, 1H, –OCH), 3.44 (m, 1H, –OCH), 2.76
(m, 2H, –CH2), 1.58–1.21 (m, 6H, 3 –CH2), 1.27 (t, 3H,
J = 7.0 Hz, –OCH2CH3) 1.12 (d, 3H, J = 6.1 Hz, –CH3)
ppm; ESI–MS: m/z = 325 [(M ? H)?].
To a cooled (0 °C) suspension of 0.41 g NaH (17.28 mmol,
4.0 eq 60 % w/w dispersion in paraffin oil) in 15 cm3 dry
THF, a solution of 1.4 g 9 (4.32 mmol, 1.0 eq) in 5 cm3
dry THF was added and stirred for 30 min. After that
0.78 cm3 BnBr (6.48 mmol, 1.2 eq) was added dropwise at
0 °C and stirred for 4 h at 25 °C. Saturated aq. NH4Cl
solution (20 cm3) was added dropwise at 0 °C followed by
30 cm3 EtOAc. Organic layers were washed with 20 cm3
water, 20 cm3 brine, dried (Na2SO4), and evaporated. The
residue was purified by column chromatography (silica gel,
60–120 mesh, 8 % EtOAc in pet. ether) to give 10 (1.59 g,
89 %) as a light yellow syrup. [a]D = -166.3 (c = 1.0,
(R)-Ethyl 7-(4-methoxybenzyloxy)-3-oxooctanoate
(8, C18H26O5)
To the stirred solution of 2.5 g 4 (7.71 mmol, 1.0 eq) in
25 cm3, anhydrous CH2Cl2 MS powder and 8.7 g PDC
(23.14 mmol, 3.0 eq) were added, to that (4–5 drops) Ac2O
was added and the whole reaction mixture was put for
reflux for 10 h. The reaction mixture was concentrated and
purified by column chromatography (silica gel, 60–120
mesh, 10 % EtOAc in pet. ether) to afford 8 (2.01 g, 81 %)
as a yellow colored thick syrup. 1H NMR (300 MHz,
CDCl3): d = 7.23 (d, 2H, J = 8.6 Hz, ArH-PMB), 6.87 (d,
2H, J = 8.6 Hz, ArH-PMB), 4.47 (s, 2H, J = 10.8 Hz,
benzylic), 4.11 (q, 2H, J = 6.9 Hz, –OCH2), 3.67 (s, 3H, –
OCH3), 3.36 (m, 1H, –OCH), 3.31 (s, 2H, –CH2), 2.19 (t,
2H, J = 6.6 Hz, –CH2), 1.44–1.24 (m, 4H, 2 CH2), 1.21 (t,
3H, J = 6.9 Hz, –OCH2CH3) 1.11 (d, 3H, J = 6.1 Hz, –
CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 199.8,
170.8, 158.3, 130.1, 129.3, 113.3, 79.1, 62.2, 56.1, 49.3,
44.6, 36.7, 22.8, 22.3, 14.6 ppm; ESI–MS: m/z = 323
[(M ? H)?].
1
CHCl3); H NMR (CDCl3, 300 MHz): d = 7.27 (m, 5H,
ArH-Bn), 7.18 (d, 2H, J = 8.3 Hz, ArH-PMB), 6.84 (d,
2H, J = 8.3 Hz, ArH-PMB), 4.56 (d, 1H, J = 11.4 Hz,
benzylic), 4.48 (s, 2H, benzylic), 4.36 (d, 1H, J = 11.4 Hz,
benzylic), 4.11 (q, 2H, J = 7.3 Hz, –OCH2), 3.69 (s, 3H, –
OCH3), 3.59 (m, 1H, –OCH), 3.39 (m, 1H, –OCH), 2.71
(dd, 1H, J = 8.1, 15.1 Hz, –CH), 2.53 (dd, 1H, J = 5.1,
15.1 Hz, –CH), 1.66–1.31 (m, 6H, 3 CH2), 1.27 (t, 3H,
J = 7.0 Hz, –OCH2CH3), 1.14 (d, 3H, J = 6.1 Hz, –CH3)
ppm; 13C NMR (CDCl3, 100 MHz): d = 170.9, 159.6,
146.7, 139.3, 129.8, 129.6, 129.1, 128.5, 128.0, 127.8,
114.0, 75.9, 73.1, 71.3, 69.9, 60.3, 55.4, 40.4, 36.8, 36.0,
ꢀ
23.3, 21.2, 14.9 ppm; IR (neat): V = 2928, 2862, 2105,
1613, 1514 cm-1; ESI–MS: m/z = 437 [(M ? Na)?].
(3S,7R)-3,7-Bis(4-methoxybenzyloxy)octanoic acid
(11, C23H30O5)
(3S,7R)-Ethyl 3-hydroxy-7-(4-methoxybenzyloxy)octanoate
(9, C18H28O5)
To a solution of 1.65 g 10 (3.98 mmol, 1.0 eq) in 10 cm3
THF: MeOH: water (3:1:1), 0.29 g LiOH (18.48 mmol,
4.6 eq) was added and stirred at 25 °C for 4 h. The pH of
reaction mixture was adjusted to acidic with 1 N HCl
solution and extracted with 30 cm3 ethyl acetate. Organic
layers were washed with 15 cm3 water, 15 cm3 brine, dried
(Na2SO4), evaporated under reduced pressure, and purified
the residue by column chromatography (silica gel, 60–120
To the stirred solution of 1.9 g 8 (4.96 mmol, 1.0 eq) in
5.0 cm3, anhydrous methanol was treated with catalytic
amount of RuCl2 [(S)-binap] [17] at 30 °C for 36 h under
hydrogen atmosphere. After completion of the reaction, it
was filtered, evaporated, and purified by column chro-
matography (silica gel, 60–120 mesh, 15 % EtOAc in pet.
ether) to give 9 (1.56 g, 81 %) as a pale yellow syrup.
123