488
J Chem Crystallogr (2014) 44:487–492
Table 1 13C NMR signals of compound 2–4 (d ppm)
0 °C and the mixture was stirred until starting material was
consumed and the color of the oxidant remained. Isopro-
panol (3 ml) was added, the mixture was stirred for
15 min, poured into cold aqueous NaCl solution and
extracted with ethyl acetate (3 9 30 ml). The organic layer
was washed with saturated NaCl solution (2 9 30 ml),
dried (anh. Na2SO4) and evaporated to afford 978 mg
(97%) of the desired ketone. Mp 174–175 °C (from ethyl
acetate) Lit. 177–179 °C [11]. 1H NMR (400 MHz,
CDCl3) d (ppm): 4.96 (d, J = 2.7 Hz, 1H), 4.60–4.49 (m,
1H), 3.64 (s, 3H, CH3O), 2.49 (t, J = 12.6 Hz, 1H), 2.01
(s, 3H), 1.99 (s, 3H), 1.01 (s, 3H), 1.00 (s, 3H), 0.82 (t,
J = 8.0 Hz, 3H). For 13C NMR (100.5 MHz) see Table 1.
Methyl 3a,7a-dihydroxy-12-oxo-5b-cholanate (4). The
acetylated ketone (3) (1.008 g, 2 mmol) was stirred in a
10 % NaOCH3 solution (8 ml) for 24 h at room tempera-
ture. After neutralization with concentrated HCl, water
(20 ml) was added and the mixture was extracted with
ethyl acetate (2 9 25 ml). The organic layer was washed
with saturated NaCl solution, dried (anh. Na2SO4) and
evaporated to afford the desired dihydroxylated ketone.
Chromatographic purification in a column packed with
silica gel employing hexane/ethyl acetate 10/1 to 4/1 as
eluent afforded 722 mg (86 %). Mp 157–158C °C (from
ethyl acetate) Lit. 154.5–161.5 °C [12]. 1H NMR
(400 MHz, CDCl3) d (ppm): 3.91 (d, J = 1.9 Hz, 1H),
3.64 (s, 3H, CH3O), 3.41 (qd, J = 11.2, 5.7 Hz, 1H), 2.44
(dd, J = 20.3, 8.0 Hz, 1H), 1.00 (s, 3H), 0.97 (s, 3H), 0.83
(d, J = 6.6 Hz, 3H). For 13C NMR (100.5 MHz) see
Table 1.
2
3
4
C-1
34.5
34.5
35.3
30.4
71.6
39.6
41.1
34.9
67.9
39.3
36.9
35.8
37.7
C-2
26.7
26.5
C-3
74.1
73.5
C-4
34.8
34.8
C-5
42.1
40.4
C-6
31.3
31.3
C-7
70.8
70.4
C-8
38.1
37.8
C-9
28.2
37.8
C-10
C-11
C-12
C-13
C-14
C-15
C-16
C-17
C-18
C-19
C-20
C-21
C-22
C-23
C-24
CH3 acetyl
C=O acetyl
OCH3
34.4
35.5
28.6
37.5
72.7
213.9
57.0
214.8
56.9
53.3
23.8
27.5
46.3
11.5
22.2
35.6
18.5
30.5
31.2
174.7
–
46.6
40.9
53.0
23.0
23.7
27.3
27.3
47.2
46.3
12.5
11.5
22.5
22.1
35.0
35.4
17.4
18.5
30.8
30.4
31.0
31.1
174.6
21.5, 21.7
170.5, 170.6
51.5
174.5
21.4, 21.4
170.1, 170.6
51.5
–
51.4
X-ray Crystallography
to a suspension of methyl cholate (1) (6.4 g, 15 mmol) in
benzene (30 ml) and the mixture was stirred for 24 h
before pouring into water (300 ml). Ethyl acetate (100 ml)
was added and the organic layer was washed with water
(4 9 30 ml) and with 50 ml portions of 10 % aq. CuSO4
(until no change in the color of CuSO4 was observed),
washed again with water (3 9 50 ml), dried (anh. Na2SO4)
and evaporated to afford 5.17 g (68 %) of the desired
diacetate (2) after purification in a chromatographic col-
umn packed with silica gel employing hexane/ethyl acetate
10/1 to 4/1 as eluent. Mp 183–185 °C (from ethyl acetate)
Lit. 185–187 °C [11]. 1H NMR (400 MHz, CDCl3) d
(ppm): 4.89 (dd, J = 5.9, 3.1 Hz, 1H), 4.58 (tt, J = 11.4,
4.4 Hz, 1H), 4.00 (s, 1H), 3.65 (s, 3H, CH3O), 2.37 (ddd,
J = 15.0, 10.0, 5.0 Hz, 1H), 2.28–2.16 (m, 2H), 2.06 (s,
3H), 2.02 (s, 3H), 0.97 (d, J = 6.3 Hz, 3H), 0.92 (s, 3H),
0.68 (s, 3H). For 13C NMR (100.5 MHz) see Table 1.
Methyl 3a,7a-diacetoxy-12-oxo-5b-cholanate (3) An
excess of Jones reagent was added dropwise to a solution
of compound 2 (506 mg, 1 mmol) in acetone (60 ml) at
A suitable single crystal of compound 4 grown by slow
evaporation of a hexane/ethyl acetate solution was moun-
ted on a glass fiber and crystallographic data were collected
with an Oxford Diffraction Gemini ‘‘A’’ diffractometer
˚
with a CCD area detector (kMoKa = 0.71073 A, mono-
chromator: graphite) at 130 K. Unit cell constants were
determined with a set of three runs of 15 frames (1° in x).
The collected data set consisted of 3 runs of 325 frames of
intensity (1° in x), and a crystal-to-detector distance of
55.00 mm. The double pass method of scanning was used
to exclude any noise. The collected frames were integrated
by using an orientation matrix determined from the narrow
frame scans.
CrysAlisPro and CrysAlis RED software packages [13]
were used for data collection and data integration. Analysis of
the integrated data did not reveal any decay. Final cell con-
stants were determined by a global refinement of 2,193
reflections (h \ 26.0°). Collected data were corrected for
absorption effects by using an Analytical numeric absorption
123