R. J. Payne et al. /Bioorg. Med. Chem. 12 (2004) 5785–5791
5789
3.9mmol) in ether (3.7mL) was added and the reaction
stirred in ice for a further 2h. The ice bath was removed
and the mixture allowed to warm to rt with stirring over
3h. The reaction was quenched with 10% aqueous HCl
and the ether layer separated. The aqueous phase was
back extracted with ether and the combined organic
fractions washed with water, saturated aqueous NaH-
CO3, water, dried (MgSO4) and evaporated under re-
duced pressure. The residue was purified by flash
chromatography on silica (ethyl acetate/petroleum ether
5:95) to give 6 (0.33g, 34%) as an orange oil. Rf (1:4 v/v
ethyl acetate–petroleum ether) = 0.61. FT-IR 2988,
ArH), 8.04 (m, 2H, ArH). 2H NMR (46MHz,
CHCl3 + 1% CDCl3) d 3.79 (br s, CD2O–). HRMS calcd
for C13H13O2Br: 248.1382. Found: 248.1389.
5.4. 2-(3-Methyl-1,4-dimethoxynaphthalen-2-yl)ethyl
hydrogen succinate 8a and 2-(3-methyl-1,4-dimethoxy-
naphthalen-2-yl)eth-[2,2-D]-yl hydogen succinate 8b
A solution of recrystallised succinic anhydride (23mg,
0.23mmol), DMAP (1mg, 0.01mmol) and triethylamine
(0.02mL, 0.16mmol) in CH2Cl2 (0.4mL) was added
drop wise to a solution of 7a (27mg, 0.11mmol, 1equiv)
in CH2Cl2 (1mL) and the reaction stirred at rt over-
night. The solvent was removed by evaporation under
reduced pressure and the resulting solid was dissolved
in CH2Cl2. This was washed with 10% aqueous HCl,
water (·2) and solvent removed to give 8a (21mg,
2941, 2837, 1732, 1595cmÀ1 1H NMR (500MHz,
.
CDCl3): d 1.26 (t, J = 5.4Hz, 3H, OCH2CH3), 2.36 (s,
3H, ArCH3), 3.87 (s, 3H, OCH3), 3.91 (s, 3H, OCH3),
3.92(s, H2, ArCH
2), 4.19 (q, J = 7.3Hz, 2H,
OCH2CH3), 7.48 (m, 2H, ArH), 8.06 (m, 2H, ArH).
13C NMR (75MHz, CDCl3): d 12.54, 14.13, 32.97,
60.80, 61.30, 62.23, 122.13, 122.36, 124.01, 125.37,
125.92, 126.54, 126.93, 128.17, 150.01, 150.66, 171.64.
HRMS calcd for C17H20O4: 288.1362. Found:
288.1366. Anal. Calcd for C17H20O4: C, 70.81; H, 6.99.
Found C, 70.51; H, 7.03.
1
55%) as a yellow oil that was not purified further. H
NMR (500MHz, CDCl3): d 2.45 (s, 3H, ArCH3), 2.66
(m, 4H, 2· CH2), 3.17 (t, J = 7.3Hz, 2H, ArCH2), 3.86
(s, 3H, OCH3), 3.91 (s, 3H, OCH3), 4.29 (t, J = 7.3Hz,
2H, CH2O), 5.29 (s, 1H, OH), 7.47 (m, 2H, ArH), 8.03
(m, 2H, ArH). 13C NMR (75MHz, CDCl3): d 12.48,
26.68, 28.85 (·2), 61.30, 62.14, 63.93, 122.18, 122.27,
125.43, 125.81, 126.12, 126.49, 127.01, 127.92, 150.15,
150.89, 172.13, 177.93. HRMS calcd for C19H22O6:
346.1416 found: 346.1420. Anal. Calcd for C19H22O6:
C, 65.9; H, 6.4. Found: C, 66.3; H, 6.8.
5.3. 2-(3-Methyl-1,4-dimethoxynaphthalen-2-yl)ethanol
7a and 2-(3-methyl-1,4-dimethoxynaphthalen-2-yl)-
ethan-[2,2-D]-ol 7b
A solution of ester 6 (110mg, 0.38mmol) in ether
(3.60mL) was stirred under an argon atmosphere, lith-
ium aluminium hydride (29mg, 0.76mmol) was added
and the reaction stirred at rt for 20min. TLC analysis
showed the reaction to be incomplete so additional lith-
ium aluminium hydride (10mg) was added and the reac-
tion stirred for a further 30min. The reaction was
quenched by the addition of saturated aqueous NH4Cl
and the organic layer separated. The aqueous phase
was back extracted with ethyl acetate and the combined
organic fractions washed with water, brine, dried
(MgSO4) and evaporated under reduced pressure. The
residue was purified by radial chromatography eluting
with 1:4 ethyl acetate–petroleum ether to 1:1 ethyl ace-
tate–petroleum ether to give 7a (85mg, 90%) as a white
solid, which was used subsequently without further puri-
fication. mp 66–69ꢁC. Rf (1:4 v/v ethyl acetate–petro-
leum ether) = 0.14. FT-IR 3265, 2936, 2841, 1589
A solution of recrystallised succinic anhydride (23mg,
0.23mmol), DMAP (1mg, 0.01mmol) and triethylamine
(0.02mL, 0.16mmol) in CH2Cl2 (0.4mL) was reacted
with 7b (27mg, 0.11mmol) in CH2Cl2 (1mL) as de-
scribed for 8a above to give 8b (31mg, 45%) as an or-
1
ange oil. H NMR (500MHz, CDCl3): d 2.45 (s, 3H,
CH3), 2.66 (m, 4H, 2· CH2), 3.16 (s, 2H, ArCH2),
3.87 (s, 3H, OCH3), 3.92(s, 3H, OCH ), 5.29 (s, 1H,
3
OH), 7.47 (m, 2H, ArH), 8.04 (m, 2H, ArH). 2H
NMR (300MHz, CHCl3 + 1% CDCl3) d 4.22 (br s,
CD2O–). HRMS calcd for C19H20D2O6: 348.1542.
Found: 348.1547.
5.5. 2-(3-Methyl-1,4-naphthoquinon-2-yl)ethyl hydrogen
succinate 9a and 2-(3-methyl-1,4-naphthoquinon-2-yl)-
eth-[2,2-D]-yl hydrogen succinate 9b
cmÀ1
.
1H NMR (500MHz, CDCl3): d 2.43 (s, 3H,
An ice cooled solution of ceric ammonium nitrate
(CAN) (230mg, 0.42mmol) in acetonitrile/water
(0.75mL of a 1:1 v/v mixture) was added drop wise to
a cooled solution of 8a (58mg, 0.17mmol) in acetonit-
rile/water (0.65mL of a 2:1 v/v mixture). The reaction
mixture was stirred for 20min at 0ꢁC, and then at rt
for a further 10min. Water was added and the mixture
was extracted with CH2Cl2 (·2). The combined organic
fractions were washed with water, dried (MgSO4) and
the solvent removed under reduced pressure. The resi-
due was purified by radial chromatography eluting with
dichloromethane to 1:19 MeOH–petroleum ether to give
9a (40mg, 76%) as a bright yellow oil. 1H NMR
(500MHz, CDCl3): d 2.19 (s, 3H, ArCH3), 2.55 (m,
4H, 2· CH2), 2.96 (t, J = 5.9Hz, 2H, ArCH2), 4.21 (t,
J = 6.4Hz, 2H, CH2O), 7.66 (m, 2H, ArH), 8.02 (m,
2H, ArH). 13C NMR (75MHz, CDCl3): d 12.92,
ArCH3), 3.12(t, J = 6.8Hz, 2H, ArCH2), 3.85 (t,
J = 6.8Hz, 2H, CH2OH), 3.86 (s, 3H, OCH3), 3.92(s,
3H, OCH3), 7.47 (m, 2H ArH), 8.04 (m, 2H, ArH).
13C NMR (75MHz, CDCl3): d 12.54, 30.61, 61.32,
61.87, 62.62, 122.17, 122.19, 125.46, 125.72, 126.43,
126.91, 127.33, 127.81, 150.32, 150.50. HRMS
calcd for C15H18O3: 246.1256. Found: 246.1255. Anal.
Calcd for C15H18O3: C, 73.1; H, 7.4. Found C, 72.8;
H, 7.4.
A solution of ester 6 (50mg, 0.18mmol) in ether
(1.7mL) was reduced with lithium aluminium deuteride
(22mg, 0.53mmol) as described for 7a above to give 7b
(40mg, 87%) as a yellow oil. 1H NMR (500MHz,
CDCl3): d 2.43 (s, 3H, CH3), 3.12(s, H2 , ArCH 2),
3.87 (s, 3H, OCH3), 3.93 (s, 3H, OCH3) 7.26 (m, 2H,