Journal of Chemistry
7
(lit. [18] 199∼200°C); IR (KBr, cm− 1): 3460, 2850, 1680, 1200,
1100, 600; 1H NMR (600 MHz, DMSO-d6) δ:11.89 (br s, 1H,
COOH), 4.50 (br s, 1H, OH), 2.12∼2.14 (m, 2H, CH),
1.66∼1.48 (m, 12H, CH2); ESI-MS (m/z): 197 (M + 1)+.
4. Conclusion
0is study provides a simple and economical method to
synthesis 2-(3-hydroxy-1-adamantane)-2-oxoacetic acid in
60% yield from 1-adamantanecarboxylic acid over five steps.
0e reaction is mild, simple, and inexpensive, which repre-
sents a great improvement compared with previously reported
methods and has a great foreground of development.
3.2. Preparation of 3-Hydroxy-1-acetyladamantane (IV).
A mixture of pyridine (4.5 mL, 0.056 mol) and compound
III (5.5 g, 0.028 mol) was stirred in an ice-water bath for an
hour; then, acetyl chloride (10 mL, 0.138 mol) was added
dropwise to the mixture, and this solution was stirred at
25°C for 3 h. After that, pyridine hydrochloride was formed
and was filtered. 0e excess acetyl chloride of filtrate was
removed with reduced pressure, and the residue was 3-
hydroxy-1-adamantyl methacetic anhydride. A mixture of
diethyl malonate (7.4 mL, 0.042 mol) and petroleum ether
(20 ml) were added dropwise to metallic sodium in pe-
troleum ether (100 mL). 0e mixture was stirred for an-
other 15 h at room temperature to get white precipitates.
Afterwards, previously prepared 3-hydroxy-1-adamantyl
methacetic anhydride in petroleum ether (20 mL) was
added to the preceding suspension slowly; then, the mix-
ture was stirred at room temperature for 12 h. Afterwards,
water (50 ml) was added to the solution and stirred for
about 10 minutes, and the organic layers were separated
and concentrated with reduced pressure to give the oil
residue. After that, a mixed solution of acetic acid (20 ml),
water (6 ml), and sulfuric acid (2 mL) was added to the
residue obtained as above, the reaction mixture was then
refluxed for 8 h and then poured into cold water (200 mL),
which was extracted with ethyl acetate (3 ×10 mL), and the
combined organic layers were washed with water (100 mL),
dried over Na2SO4, and concentrated under reduced
pressure. 0e residue was recrystallized from methylene
chloride/hexane to give compound IV (3.69 g, 74.6%
yield).M.p. 89∼90°C(lit. [25] 89∼90°C); IR (KBr, cm− 1):
3380, 2880, 2850, 1750, 1410, 1000, 600; 1H NMR
(600 MHz, DMSO-d6) δ: 4.52 (s, 1H, OH), 2.22 (br s, 2H,
CH), 2.05 (s, 3H, CH3), 1.62∼1.47 (m, 12H, CH2); ESI-MS
(m/z): 195 (M + 1)+.
Data Availability
0e figure and table data used to support the findings of this
study are included within the article.
Conflicts of Interest
0e authors declare that there are no conflicts of interest
regarding the publication of this paper.
Authors’ Contributions
Qi Liao and Lan Jiang have contributed equally to this work.
Acknowledgments
0e authors are deeply grateful for the support of the
Chongqing Science and Technology Commission
(cstc2015zdcy-ztzx120003) for this study. 0e authors also
appreciate that the Undergraduate Innovative Experiment
Program of Chongqing Medical University (no. 201971) for
providing financial aid for our work.
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3.3. Preparation of 2-(3-Hydroxy-1-adamantyl)-2-Oxoacetic
Acid (I). 0e tert-butanol (10 mL), 2% KOH (100 mL),
compound IV (5.0 g, 0.026 mol), and phase transfer catalyst
TBAB were added to a 250 mL three-necked flask; then, the
mixture was stirred at 40°C, and potassium permanganate
(8.3 g, 0.052 mol) was added in batches during a period of
1 h. After that, the solution was stirred for 5 h; then, sodium
sulfite (3.8 g, 0.026 mol) was added and stirred for 10 min,
and the mixture was filtered. 0e filtrate was adjusted to pH
1-2 and then extracted with ethyl acetate (10 mL × 3), and the
organic phases were combined, which was concentrated
under reduced pressure to get a light yellow oil residue. 0e
residue was recrystallized by heptane and dried to obtain
compound I (5.3 g, 91.8% yield). M.p. 163–165°C (lit. [26]
164∼165°C); IR (KBr, cm− 1): 3380, 2920, 2850, 1713, 1680;
1H NMR (600 MHz, DMSO-d6) δ: 14.2 (br s, 1H, COOH),
4.6 (br s, 1H, OH), 2.19 (s, 2H, CH), 1.72–1.46 (m, 12H,
CH2); ESI–MS (m/z): 225(M + 1)+.