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6.6-6.8 (m, 2 H), 7.15-7.35 (m, 2 H). IR (cm-1) 2950 (s),
1650 (s), 1530 (m), 1495 (s), 1250 (s). MS (EI) 364 (85,
M+), 293 (45), 186 (100), 119 (64).
3-Methoxy-21-phenyl-19-nor-pregna-1,3,5(10),14,16-
pentaen-20-one (7): 1H NMR (CDCl3, 300 MHz) 1.0-1.15
(m, 1 H), 1.25 (s, 3 H), 1.55-1.70 (m, 1 H), 1.8-1.95 (m,
1 H), 2.15-2.4 (m, 4 H), 2.55-2.65 (m, 1 H), 2.9-3.1 (m,
2 H), 3.8 (s. 3 H), 4.0 (s, 2 H), 6.10 (m, 1 H), 6.6-6.8 (m,
2 H), 7.15-7.4 (m, 7 H). IR (cm-1) 2950 (m), 1650 (s),
1520 (s), 1500 (s), 1250 (s).
10 mL of warm ethyl acetate. Complete evaporation of the
solvent gave the product as a colourless oil. Yield: 1.62 g
(8.91 mmol, 90%) of diene-yne 15 (Cyclohex-1-enylethyn-
1
ylbenzene). H NMR (CDCl3, 300 MHz) 1.55-1.8 (m, 4
H), 2.1-2.2 (m, 2 H), 2.2-2.3 (m, 2 H), 6.15-6.25 (m, 1
H), 7.2-7.3 (m, 3 H), 7.35-7.45 (m, 2 H). IR (cm-1) 2950
(s), 1595 (m), 1495 (s), 760 (s), 695 (s). MS (CI/NH3 ) 200
(70, M+ + NH4+), 183 (100, M+ + 1), 162 (9), 145 (12).
The Following Compounds Were Prepared by the
Same Procedure. 3-Methoxy-17-prop-1-ynylestra-1,3,5-
1
Procedure for the Rupe Rearrangement of Steroid 2
in the Pilot Plant. In a 500-L enamelled reaction vessel, 64
kg of cation-exchange resin A-252 C and 128 L of ethanol
were charged. The mixture was stirred for 1 h. The resin
was filtered off using a 200-L pressure filter and washed
with 220 L of deionized water. The resin was taken back
into the vessel, and 117 L of deionized water and 6.4 L of
concentrated sulfuric acid were added, and the mixture was
stirred for 1 h. The resin was filtered off using the pressure
filter and washed neutral with deionized water. The activated
resin was returned to the vessel. Steroidal derivative 1 (64
kg) and 256 L of ethyl acetate were added. Ethyl acetate/
water (130 l) was distilled off and replaced by 130 L of ethyl
acetate. This step was repeated once, and then the water
content was measured and adjusted to 2 mol equiv by
addition of deionized water. The reaction mixture was
refluxed for 4 h after which time TLC control showed
complete conversion of the starting material. The resin was
filtered off using a preheated 200-L pressure filter and was
washed four times with 50 L of ethyl acetate; 250 L of the
filtrate was distilled off, and then the mixture was cooled to
0 °C and stirred for 1 h. The crystals were isolated with a
centrifuge, washed with 50 L of cold ethyl acetate, and dried
in a drying cabinet at 50 °C. A total yield of 49.8 kg (77.8%)
of colourless crystals was obtained with high purity (98.3%).
General Procedure for the Elimination of Propargylic
Alcohols to Diene-Yne Compounds Catalyzed by Strongly
Acidic Cation-Exchange Resins. Strongly acidic cation-
exchange resin (type IR-120 H) (2 g) was stirred in 10 mL
of EtOH for 30 min at 20 °C, filtered, washed with water,
and stirred for another 30 min in 2 N sulfuric acid. After
filtration and washing with water, the activated cation-
exchange resin together with 2 g of propargylic alcohol 14
(rac-1-(2-phenylethynyl)-cyclohexane-1-ol) (9.99 mmol) was
suspended in 10 mL of ethyl acetate and warmed to 80 °C.
Ethyl acetate (10 mL) was distilled off, and the same amount
of fresh ethyl acetate was added. This was repeated once.
After 9 h at 80 °C, the TLC control showed that the reaction
was complete. The resin was filtered off and washed with
(10),14,16-pentaene (9): fp: 93 °C. H NMR (CDCl3, 300
MHz) 0.85-0.95 (m, 1 H), 1.10 (s, 3 H), 1.55-1.70 (m, 2
H), 1.8-1.95 (m, 1 H), 2.05 (s, 3 H), 2.15-2.4 (m, 4 H),
2.9-3.1 (m, 2 H), 3.8 (s, 3 H), 6.0 (m, 1 H), 6.6-6.8 (m, 2
H), 7.4-7.5 (m, 2 H). IR (cm-1) 2950 (s), 1610 (m), 1500
(s), 1250 (s). MS (EI) 304 (100, M+), 289 (21), 186 (95),
174 (52).
3-Methoxy-17-(2-phenylethynyl)estra-1,3,5(10),14,16-
pentaene (11): 1H NMR (CDCl3, 300 MHz) 0.85-0.95 (m,
1 H), 1.20 (s, 3 H), 1.55-1.70 (m, 2 H), 1.8-1.95 (m, 1 H),
2.15-2.4 (m, 4 H), 2.9-3.1 (m, 2 H), 3.8 (s, 3 H), 6.0 (m,
1 H), 6.6-6.8 (m, 2 H), 7.2-7.35 (m, 5 H), 7.4-7.5 (m, 2
H). IR (cm-1) 2950 (s), 2200 (m), 1600 (s), 1500 (s), 1250
(s). MS (CI/NH3) 368 (45, M+ + 1), 367 (100, M+).
3-Methoxy-17-prop-1-ynylestra-1,3,5(10),16-tetraene
1
(13): H NMR (CDCl3, 300 MHz) 0.87 (s, 3 H), 1.5-2.1
(m, 5 H), 2.0 (s, 3 H), 2.15-2.4 (m, 4 H), 2.8-3.0 (m, 2
H), 3.8 (s, 3 H), 5.9 (br s, 1 H), 6.6-6.8 (m, 2 H), 7.2-7.35
(m, 1 H). MS (CI/NH3) 324 (19, M+ + NH3), 308 (25,
M+ + 1), 307 (100, M+).
Cyclohex-1-enylethynylbenzene (15): 1H NMR (CDCl3,
300 MHz) 1.5-1.7 (m, 4 H), 2.4-2.6 (m, 4 H), 6.15-6.2
(m, 1 H), 7.2-7.3 (m, 3 H), 7.4-7.5 (m, 2 H). IR (cm-1)
2950 (s), 2250 (w), 1600 (m), 1495 (s), 1450 (s), 760 (s),
695 (s). MS (EI) 183 (100, M+ + 1), 162 (10), 145 (15).
Cyclopent-1-enylethynylbenzene (17): 1H NMR (CDCl3,
300 MHz) 1.9-2.0 (m, 2 H), 2.4-2.6 (m, 4 H), 6.15-6.2
(m, 1 H), 7.2-7.3 (m, 3 H), 7.4-7,5 (m, 2 H). IR (cm-1)
2950 (s), 2250 (w), 1600 (m), 1495 (s), 1450 (s), 760 (s),
695 (s). MS (EI) 168 (95, M+), 167 (100), 152 (55), 95 (52).
Acknowledgment
Excellent technical assistance by Ms. Tanja Hoffmann is
gratefully acknowledged. We thank the Schering Analytical
and Spectroscopic Departments for measuring the spectro-
scopic data and for HPLC support.
Received for review August 10, 2001.
OP010063H
Vol. 6, No. 3, 2002 / Organic Process Research & Development
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