3
66
S. K. PICHANDI MOHANRAJ ET AL.
product obtained after distilling out methanol was extracted in to dichloromethane (2 X
7
8
.5 L), washed with water up to neutral pH, evaporated and dried to give 15 (1.785 kg,
1
8% yield, 98.67% purity from HPLC analysis) as an oil. H NMR (300 MHz, CD OD)
3
d 0.76 (s, 3H), 0.91-2.84 (m, 30H), 3.53 (t, 2H), 3.66 (t, 1H), 6.47 (s, 1H), 6.54 (dd,
1
3
1
2
3
1
4
H), 7.06 (d, 1H). C NMR (75 MHz, CD OD) d 26.56, 26.91, 28.59, 29.20, 29.47,
3
9.97, 30.50, 30.59, 30.65, 30.71, 30.76, 31.06, 33.59, 34.56, 35.27, 35.63, 35.73, 38.15,
9.48, 40.34, 41.13, 43.56, 44.43, 61.46, 62.95, 69.72, 72.07, 79.88, 81.40, 82.46, 113.92,
16.94, 127.79, 131.65, 137.43, 155.84, 178.56; MS (M-H): Calculated for C H O , m/z
27
42 3
14.62. Found, m/z 413.20.
Anal. Calcd for C H O : C, 78.21; H, 10.21. Found: C, 78.23; H, 10.17.
2
7
42 3
3
-Triphenylmethyloxy-7a-9-(hydroxynonyl)estra-1,3,5(10)-triene-17b-ol (16)
To a solution of 1.785 kg, (4.3 mol) of 15 in tetrahydrofuran (17.85 L) was added 1.430 L
of 6N sodium hydroxide solution followed by trityl chloride (1.6 kg, 5.73 mol) and the
reaction mixture was stirred for 4 hours at room temperature. The reaction mixture was
poured into saturated sodium bicarbonate solution (6 L). The product was extracted
with dichloromethane (2 X 10 L) and the organic layer washed to neutral with water,
ꢀ
concentrated completely under vacuum at 40-45 C to yield crude compound 16 as a
gummy material. This was dissolved in 5 L of dichloromethane at ambient temperature
ꢀ
and then was added 35L of petroleum ether slowly. The contents were cooled to -10 C
to crystallize pure compound 16 (2.74 kg, yield 97%, 98.64% purity from HPLC ana-
1
lysis). H NMR (300 MHz, DMSO-d6) d 0.73 (s, 3H), 0.8-2.64 (m, 32H), 3.64 (t, 2H),
3
.69 (t, 1H), 6.29 (s, 1H), 6.45 (d, 1H), 6.85 (d, 1H), 7.20 (t, 3H), 7.25 (t, 6H), 7.44
1
3
(d, 6H). C NMR (75 MHz, DMSO-d6) d 11.21, 22.57, 25.37, 25.72, 26.87, 28.06, 29.43,
2
8
1
9.64, 29.70, 29.99, 30.49, 32.76, 33.09, 34.35, 36.83, 38.13, 41.77, 43.31, 46.41, 63.05,
1.94, 90.16, 118.32, 122.37, 125.48, 126.97, 127.51, 129.02, 132.36, 135.55,
44.31, 153.90.
Anal. Calcd for C H O : C, 84.10; H, 8.59. Found: C, 84.02; H, 8.64.
4
6
56 3
3
-Triphenylmethyloxy-7a-(9-p-toluenesulfonyloxynonyl)estra-1,3,5(10)-triene-17b-
ol (17)
To a stirred solution of compound 16 (1.124 kg, 1.71 mol) in dichloromethane (5.6 L) at
ꢀ
-
(
10 C was added triethylamine (0.61 kg, 6.0 mol) followed by p-toluenesulfonyl chloride
ꢀ
763 g, 4.0 mol). The reaction mixture was stirred at -10 C for 24 hours. The mixture
was concentrated, diluted with methanol (3 L) and poured into saturated sodium bicar-
bonate (4.5L) solution, stirred vigorously for one hour and the product was extracted
into dichloromethane (2 X 7 L), the organic phase washed with water until neutral and
evaporated to obtain gummy solid 17 (1.34 kg, yield 97%, 89.01% purity from HPLC
1
analysis). The material was used directly in the next step. H NMR (400 MHz, DMSO-
d6) d 1.21-1.30 (m, 15H), 1.60-1.65 (m, 3H), 1.84 (d,1H), 2.07-2.20 (m,4H), 2.44 (s,
4
7
7
H), 2.62 (dd, 1H), 3.70 (q, 1H), 4.02 (t, 2H), 6.29 (d,1H), 6.44, (dd, 1H), 6.85 (d, 1H),
.20 (s, 1H), 7.21 (m, 2H), 7.23 (m, 3H), 7.25 (m, 3H), 7.27 (m, 1H), 7.33 (d, 2H),
.426-7.449 (m, 6H), 7.80Hz, (2H d)