Improved microwave-assisted ring opening of 1,1,1-trifluoro-2,3- epoxypropane: Synthesis of new 3-alkoxy-1,1,1-trifluoropropan-2-ols

Article abstract of DOI:10.1055/s-0030-1258156

A highly efficient and environmentally friendly method for the synthesis of 3-alkoxy-1,1,1-trifluoropropan-2-ols is presented. The approach involves ring-opening reaction of 1,1,1-trifluoro-2,3-epoxypropane with structurally different long-chain alcohols

Full text of DOI:10.1055/s-0030-1258156

PAPER
3117
Improved Microwave-Assisted Ring Opening of 1,1,1-Trifluoro-2,3-
epoxypropane: Synthesis of New 3-Alkoxy-1,1,1-trifluoropropan-2-ols
M
icrowa
v
o
e-Assiste
d
S
s
ynthesis
o
e
f
Trifluorom
p
ethyl Carbinols Rayó,a Lourdes Muñoz,a Gloria Rosell,b Mª Pilar Bosch,a Ángel Guerrero*a
a
Department of Biological Chemistry and Molecular Modelling, IQAC (CSIC), Jordi Girona 18–26, 08034 Barcelona, Spain
Department of Pharmacology and Therapeutic Chemistry, Unity Associated to CSIC, Faculty of Pharmacy, University of Barcelona,
Avda. Diagonal s/n., 08028 Barcelona, Spain
b
Fax +34(932)045904; E-mail: angel.guerrero@iqac.csic.es
Received 14 May 2010; revised 20 May 2010
O
Abstract: A highly efficient and environmentally friendly method
for the synthesis of 3-alkoxy-1,1,1-trifluoropropan-2-ols is present-
ed. The approach involves ring-opening reaction of 1,1,1-trifluoro-
2,3-epoxypropane with structurally different long-chain alcohols
under microwave irradiation at room temperature in the absence of
solvent. These chemicals are precursors of the corresponding tri-
fluoromethyl ketones, potent inhibitors of human and murine liver
microsomes and porcine liver esterase.
CF3
O
2
OH
CF3
RO
RO
+
CF3
4
ROH
3
1
Scheme 1 Ring opening of 1,1,1-trifluoro-2,3-epoxypropane (2)
with alcohols 3
Key words: 1,1,1-trifluoro-2,3-epoxypropane, ring opening, tri-
fluoromethyl carbinols, trifluoromethyl ketones, microwave catalysis
ring-opening reaction to prepare also long-chain trifluo-
romethyl carbinols. The results of this investigation are
reported herein.
Trifluoromethyl carbinols are important intermediates in
the synthesis of polyfunctional bioactive molecules1 and
have been used as synthons in the construction of anti-fer-
roelectric liquid crystalline molecules.2 They are also pre-
cursors of trifluoromethyl ketones (TFMK), an important
class of compounds, which have resulted potent inhibitors
of hydrolytic enzymes including carboxylesterases,3 pro-
teases,4 human phospholipases,5 fatty acid amide hydro-
lase,6 etc. Hammock and co-workers found that the
introduction of a heteroatom (S, O) in the b-position to the
carbonyl group increased the inhibition potency of these
compounds, producing potent inhibitors of human liver
microsomes, murine liver microsomes, and porcine liver
esterase.7 Very few papers have described the synthesis of
ether-substituted TFMK 4.5,7 In this paper, we present a
straightforward, environmentally friendly approach for
the synthesis of 3-alkoxy-1,1,1-trifluoropropan-2-ols 1,
many of them previously unknown in the literature, pre-
cursors of 4. The approach involves microwave-induced
ring cleavage of 1,1,1-trifluoro-2,3-epoxypropane (2)
with long-chain alcohols 3 in the presence of a Lewis acid
as catalyst (Scheme 1). Since the pioneering work by
McBee et al.8 in 1956 on the ring cleavage of 1,1,1-tri-
fluoro-2,3-epoxypropane with ethanol, there have been
only a further few reports and these used simple alcohols
(MeOH, EtOH, BnOH) in the presence of sulfuric acid.9–11
Moreover, when longer chain alcohols were used, such as
hexan-1-ol, the expected ring-opening product resulted in
low yield (47%).9 Therefore, we envisioned that micro-
wave irradiation could improve the performance of the
Initial trials for the reaction of (Z)-tetradec-9-en-1-ol (3e)
with fluorinated epoxide 2 under Lewis acid catalysts
(Table 1), such as copper(I) cyanide and aluminum(III)
chloride, in tetrahydrofuran at 45 °C for 48 hours failed to
produce the expected trifluoromethyl carbinol 1e (entries
1 and 2). When the reaction was conducted at room tem-
perature for 24 hours using boron trifluoride–diethyl ether
complex as the catalyst in dichloromethane, the desired
fluorinated alcohol 1e was obtained in 43% yield along
with 51% of unreacted alcohol 3e (entry 3). Increasing the
temperature to 45 °C yielded alcohol 1e in a moderate
68% yield (entry 4). Similar results were obtained using a
shorter and, in principle, more reactive alcohol such as oc-
tan-1-ol (3a) (entries 5 and 6). To improve these results,
microwave irradiation appeared a promising alternative
(Scheme 2).
O
CF3
2
OH
BF3·OEt2
MW
+
Me(H2C)7O
CF3
1a
Me(CH2)7OH
3a
Scheme 2
Microwave-assisted alcoholysis reaction of 1,1,1-
trifluoro-2,3-epoxypropane (2) with octan-1-ol (3a)
Thus, when the reaction of epoxide 2 and octan-1-ol (3a)
in presence of 1 mol% of boron trifluoride–diethyl ether
complex and in the absence of solvent was implemented
SYNTHESIS 2010, No. 18, pp 3117–3120
Advanced online publication: 07.07.2010
DOI: 10.1055/s-0030-1258156; Art ID: Z12410SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0

3118
J. Rayó et al.
PAPER
Table 1 Optimization Experiments for the Alcoholysis Reaction of 1,1,1-Trifluoro-2,3-epoxypropane (2)
Entry
Alcohola
3e
Ratio 2/3
1:0.8
Catalyst
CuCN
Temp (power, time)b
45 °C (–, 48 h)
Solvent
THF
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
–
Yieldc (%)
1
2
3
4
5
6
7
8
9
–
3e
1:0.8
AlCl3
45 °C (–, 48 h)
–
3e
1:0.8
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
r.t. (–, 24 h)
43 (1e), 51 (3e)
68 (1e)
41 (1a), 55 (3a)
70 (1a)
53 (1a)
79 (1a)
96 (1a)
3e
1:0.8
45 °C (–, 24 h)
3a
1:0.8
r.t. (–, 24 h)
3a
1:0.8
45 °C (–, 24 h)
3a
1:0.8
45 °C (100 W, 0.25 h)
60 °C (100 W, 0.25 h)
60 °C (100 W, 0.25 h)
3a
1:0.8
–
3a
1:1.25
–
a For alcohols see Table 2.
b When applicable, power indicates initial microwave power, which is modulated to control the temperature.
c Isolated yields after column chromatography purification on silica gel.
in a microwave oven at 45 °C for 15 minutes, the expected Table 2 Microwave-Enhanced Reaction of 1,1,1-Trifluoro-2,3-ep-
oxypropane (2) with Different Alcohols
carbinol 1a was obtained in 53% isolated yield with no
unreacted substrate being detected (entry 7). Increasing
Entry
1
Alcohol
Product
Yielda (%)
96
the reaction temperature to 60 °C improved the perfor-
mance of the reaction (79% yield of 1a, entry 8). Howev-
er, the ratio of reagents used (2/3a, 1:0.8) meant that the
concomitant formation of epoxide oligomers was also ob-
served, as already found in a previous ring-opening meth-
odology of nonfluorinated epoxides.12 Increasing the ratio
2/3a to 1:1.25 under the same conditions was sufficient to
obtain compound 1a in an excellent 96% yield, with no
epoxide oligomers detected (entry 9). In the absence of the
catalyst, the starting alcohol was recovered unchanged
(entry not shown).
1a14
OH
OH
OH
5
3a
2
3
1b7
89
96
3
7
3b
1c14
3c
Et
4
1d
81
OH
The optimized methodology was applied to structurally
diverse alcohols and the results are summarized in
Table 2. Moderate- or long-chain length saturated and un-
saturated primary alcohols 3a–f, secondary 3g,h, and even
tertiary alcohols 3i provided good to excellent yields of
the corresponding fluorinated alcohols 1a–i (entries 1–9).
In the case of 3i we could not avoid, however, the undes-
ired elimination reaction. The chain length of the alcohols
had no effect on the yield of the process. Furthermore, no
isomerization product in the reaction of 3e (Z-isomer) was
detected. Benzyl alcohol (3j) also gave the expected ring-
opening product 1j in excellent yield (91%, entry 10), sig-
nificantly higher than that obtained under conventional
conditions (BF3·OEt2, BnOH, 45 °C, 65% yield).11b As
model examples of being precursors of TFMK 4, com-
pounds 1a and 1e were converted into ketones 4a and 4e
by Dess–Martin oxidation13 in 78–81% yield.
7
3d
n-Bu
OH
5
6
1e
1f
77
67
7
3e
BnO
OH
3f
OH
7
8
1g
1h
83
86
3g
3h
OH
OH
7
9
1i
69
91
In summary, the methodology described herein remark-
ably improves the performance of the ring-opening reac-
tion of 1,1,1-trifluoro-2,3-epoxypropane (2) with alcohols
3 and expands the scope of previous epoxide opening re-
actions. The reaction is very fast (15 min), provides high-
to-excellent yields of the corresponding fluorinated
3i
BnOH
3j
10
1j11b
a Isolated yields after column chromatography purification on silica
gel.
Synthesis 2010, No. 18, 3117–3120 © Thieme Stuttgart · New York

PAPER
Microwave-Assisted Synthesis of Trifluoromethyl Carbinols
3119
1H NMR (500 MHz, CDCl3): d = 4.10 (m, 1 H), 3.67–3.57 (m, 2 H),
3.49 (t, J = 6.5 Hz, 2 H), 3.21 (br s, 1 H), 2.12 (m, 4 H), 1.58 (m, 2
H), 1.45 (m, 2 H), 1.38–1.29 (m, 8 H), 1.09 (t, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 124.1 (q, J = 280 Hz, CF3), 81.6
(C), 79.5 (C), 72.0 (CH2), 69.3 (q, J = 31 Hz, CHCF3), 68.0 (CH2),
29.3 (CH2), 29.2 (CH2), 29.1 (CH2), 29.2 (CH2), 28.7 (CH2), 18.6
(CH2), 14.3 (CH3), 12.4 (CH2).
carbinols 1 under mild conditions and is environmentally
friendly (no solvent is required). The fluorinated alcohols
1 prepared can be easily oxidized to the corresponding tri-
fluoromethyl ketones 4 and therefore the outlined meth-
odology represents also a formal synthesis of these potent
enzyme inhibitors.
19F NMR (376 MHz, CDCl3): d = –78.28 (d, J = 7.9 Hz, CF3).
MS (EI): m/z (%) = 294 (M+, 1), 265 (4), 223 (9), 169 (25), 93 (100),
79 (99), 67 (99), 55 (66).
HRMS: m/z [M + H]+ calcd for C15H26F3O2: 295.1885; found:
Chemicals were purchased from Sigma-Aldrich Química. Micro-
wave reactions were carried out in a Discover apparatus (CEM,
USA). IR spectra were recorded on a Bomem MB-120. H NMR
spectra were recorded on a Varian Unity spectrometer operating at
300 or 500 MHz, 13C NMR at 75 or 100 MHz and 19F NMR at 376
MHz; TMS (1H,13C) and CFCl3 (19F) as internal standard. Mass
spectra were obtained on a Fisons MD 800 instrument. HRMS was
obtained on a UPLC Acquity (Waters, USA) instrument coupled to
a mass spectrometer LCT Premier XE.
1
295.1874.
1,1,1-Trifluoro-3-[(Z)-tetradec-9-enyloxy]propan-2-ol (1e)
IR (film): 3447, 2928, 2856, 1275, 1177, 1146 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.35 (m, 2 H), 4.11 (m, 1 H), 3.64
(m, 2 H), 3.51 (t, J = 6.6 Hz, 2 H), 2.93 (br, J = 6.1 Hz, 1 H), 2.04–
1.99 (m, 4 H), 1.58 (m, 2 H), 1.35–1.26 (m, 14 H), 0.89 (t, J = 6.5
Hz, 3 H).
1,1,1-Trifluoro-3-(octyloxy)propan-2-ol (1a); Typical Proce-
dure
Octan-1-ol (3a, 200 mg, 1.53 mmol), 1,1,1-trifluoro-2,3-epoxypro-
pane (2, 107 mg, 0.96 mmol), and freshly distilled BF3·OEt2 (2 mL,
16 mmol) were added to a microwave tube. The mixture was heated
at 60 °C in a microwave oven (100 W) for 15 min and then cooled.
The crude mixture was partitioned between Et2O (10 mL) and H2O
(10 mL). The organic soln was separated, washed with 1 M
NaHCO3 and H2O, dried (MgSO4), filtered, and concentrated. The
obtained pale yellow oil was purified by column chromatography
(silica gel, hexane–Et2O, 9:1) to afford 1a (223 mg, 96%).
13C NMR (100 MHz, CDCl3): d = 130.2 (CH), 130.1 (CH), 124.5
(q, J = 280 Hz, CF3), 72.3 (CH2), 69.6 (q, J = 31 Hz, CHCF3), 68.1
(CH2), 32.2 (CH2), 30.0 (CH2), 29.7 (CH2), 29.6 (CH2), 29.5 (CH2),
27.5 (CH2), 27.2 (CH2), 26.2 (CH2), 22.6 (CH2), 14.3 (CH3).
19F NMR (376 MHz, CDCl3): d = –78.28 (d, J = 6.9 Hz, CF3).
MS (EI): m/z (%) = 324 (M+, 3), 225 (8), 194 (30), 169 (27), 96 (97),
81 (100), 68 (99), 55 (95).
HRMS: m/z [M + H]+ calcd for C17H32F3O2: 325.2354; found:
325.2361.
IR (film): 3420, 2929, 2858, 1467, 1382, 1276, 1180, 1145, 1122,
699 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.14–4.08 (m, 1 H), 3.67 (dd,
J = 10.0, 3.5 Hz, 1 H), 3.60 (dd, J = 10.5, 6.0 Hz, 1 H), 3.51 (t,
J = 6.5 Hz, 2 H), 1.59 (m, 2 H), 1.34–1.27 (m, 10 H), 0.88 (t, J = 6.5
Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 124.2 (q, J = 280 Hz, CF3), 72.1
(CH2), 69.3 (q, J = 31 Hz, CHCF3), 67.9 (CH2), 31.8 (CH2), 29.4
(CH2), 29.3 (CH2), 29.2 (CH2), 25.9 (CH2), 22.6 (CH2), 14.1 (CH3).
19F NMR (376 MHz, CDCl3): d = –78.30 (d, J = 6.4 Hz, CF3).
MS (EI): m/z (%) = 242 (M+, 1), 143 (85), 111 (85), 84 (64), 71
(100), 57 (97), 43 (84).
HRMS: m/z [M – H]+ calcd for C11H20F3O2: 241.1415; found:
3-[3-(Benzyloxy)propoxy]-1,1,1-trifluoropropan-2-ol (1f)
IR (film): 3397, 2926, 2872, 1273, 1174, 1145 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.47–7.23 (m, 5 H), 4.50 (s, 2 H),
4.07 (m, 1 H), 3.62 (m, 6 H), 3.22 (br, 1 H), 1.89 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 138.4 (C), 128.6 (CH), 128.0
(CH), 127.9 (CH), 124.4 (q, J = 281 Hz, CF3), 73.3 (CH2), 69.5 (q,
J = 31 Hz, CHCF3), 69.3 (CH2), 67.1 (CH2), 53.7 (CH2), 29.9
(CH2).
19F NMR (376 MHz, CDCl3): d = –78.16 (d, J = 6.3 Hz, CF3).
MS (EI): m/z (%) = 278 (M+, 25), 169 (24), 147 (35), 107 (97), 91
(100), 79 (34), 65 (33).
HRMS: m/z [M – H]+ calcd for C13H16F3O3: 277.1052; found:
241.1408.
277.1042.
3-(Decyloxy)-1,1,1-trifluoropropan-2-ol (1c)
IR (film): 3420, 2930, 2858, 1275, 1146, 698 cm–1.
3-(Cyclohexyloxy)-1,1,1-trifluoropropan-2-ol (1g)
1H NMR (300 MHz, CDCl3): d = 4.11–4.05 (m, 1 H), 3.70–3.51 (m,
2 H), 3.47 (t, J = 6.0 Hz, 2 H), 3.03 (br, 1 H), 1.54 (m, 2 H), 1.27
(m, 14 H), 0.88 (t, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 124.2 (q, J = 280 Hz, CF3), 69.4
(q, J = 31 Hz, CHCF3), 65.4 (CH2), 36.3 (CH2), 31.8 (CH2), 29.6
(CH2), 29.5 (CH2), 29.2 (CH2), 25.4 (CH2), 25.3 (CH2), 22.6 (CH2),
19.4 (CH2), 19.3 (CH2), 14.1 (CH3).
19F NMR (376 MHz, CDCl3): d = –78.18 (d, J = 6.9 Hz, CF3).
MS (EI): m/z (%) = 269 ([M – 1]+, 2), 255 (14), 157 (100), 141 (34),
69 (40), 56 (70), 42 (71).
HRMS: m/z [M + H]+ calcd for C13H26F3O2: 271.1885; found:
IR (film): 3415, 2936, 2860, 1452, 1275, 1140 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.09 (m, 1 H), 3.70 (dd, J = 10.0,
5.0 Hz, 1 H), 3.63 (dd, J = 10.0, 5 Hz, 1 H), 3.33 (m, 1 H), 3.19 (br,
1 H), 1.89 (m, 2 H), 1.73 (m, 2 H), 1.52 (m, 1 H), 1.27 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 124.2 (q, J = 281 Hz, CF3), 78.6
(CH), 69.3 (q, J = 31 Hz, CHCF3), 65.1 (CH2), 31.9 (CH2), 31.7
(CH2), 25.6 (CH2), 23.8 (CH2), 23.7 (CH2).
19F NMR (376 MHz, CDCl3): d = –78.21 (d, J = 7.0 Hz, CF3).
MS (EI): m/z (%) = 212 (M+, 27), 183 (34), 169 (45), 113 (56), 83
(100), 55 (66).
HRMS: m/z [M – H]+ calcd for C9H14F3O2: 211.0946; found:
211.0942.
271.1891.
3-(Dodec-9-ynyloxy)-1,1,1-trifluoropropan-2-ol (1d)
1,1,1-Trifluoro-3-(1-methylnonyloxy)propan-2-ol (1h)
IR (film): 3443, 2934, 2858, 2246, 1275, 1145, 912, 735 cm–1.
IR (film): 3419, 2929, 2858, 1275, 1144, 909, 736 cm–1.
Synthesis 2010, No. 18, 3117–3120 © Thieme Stuttgart · New York

3120
J. Rayó et al.
PAPER
1H NMR (500 MHz, CDCl3): d = 4.08 (m, 1 H), 3.74–3.44 (m, 3 H),
3.29 (dd, J = 15.0, 6.5 Hz, 1 H), 1.56–1.26 (m, 14 H), 1.15 (d,
J = 6.0 Hz, 3 H), 0.87 (t, J = 6.5 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 5.37–5.33 (m, 2 H), 4.50 (s, 2 H),
3.78 (s, 2 H), 3.62–3.54 (m, 4 H), 2.02 (m, 4 H), 1.63 (m, 2 H), 1.30
(br, 16 H), 0.90 (t, J = 6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 124.2 (q, J = 280 Hz, CF3), 77.0
(CH), 69.4 (q, J = 31 Hz, CHCF3), 65.5 (CH2), 36.3 (CH2), 31.8
(CH2), 29.6 (CH2), 29.5 (CH2), 29.2 (CH2), 25.3 (CH2), 22.6 (CH3),
19.3 (CH2), 14.0 (CH3).
19F NMR (376 MHz, CDCl3): d = –78.20 (d, J = 7.0 Hz, CF3).
MS (EI): m/z (%) = 269 ([M – 1]+, 4), 255 (22), 157 (98), 70 (64),
13C NMR (75 MHz, CDCl3): d = 129.82 (CH), 129.68 (CH), 122.38
(qCF, J = 285 Hz CF3 hydrate), 92.23 (qCCF, J = 32.4 Hz, C(OH)2),
72.70 (CH2O hydrate), 72.49 (CH2O keto), 71.06 (CH2O keto),
69.54 (CH2O hydrate), 31.85, 29.09, 27.06, 25.77, 25.72, 22.24,
13.89.
19F NMR (282 MHz, CDCl3): d = –78.47 (s, COCF3), –85.89 (s,
C(OH)2CF3).
56 (100).
HRMS: m/z [M + H]+ calcd for C17H30F3O2: 323.2197; found:
323.2201.
HRMS: m/z [M + H]+ calcd for C13H26F3O2: 271.1885; found:
271.1872.
1,1,1-Trifluoro-3-(1-methylcyclohexyloxy)propan-2-ol (1i)
Acknowledgment
IR (film): 3447, 2934, 2861, 1274, 1175, 1143, 1123 cm–1.
We are indebted to Miriam Fuentes for technical support and Drs.
A. Delgado and A. Messeguer for the use of the microwave oven.
We also gratefully acknowledge MICINN for a fellowship to J.
Rayó, EU for a contract to L. Muñoz and CICYT (AGL2009-
13452-C02-01) for financial support.
1H NMR (300 MHz, CDCl3): d = 4.07 (m, 1 H), 3.55 (m, 2 H), 3.09
(br, 1 H), 1.71–1.17 (m, 10 H), 1.14 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 124.4 (q, J = 280 Hz, CF3), 74.7
(C), 69.4 (q, J = 30 Hz, CHCF3), 57.9 (CH2), 36.4 (CH2), 36.0
(CH2), 25.5 (CH2), 25.4 (CH2), 24.6 (CH2), 22.0 (CH3).
19F NMR (376 MHz, CDCl3): d = –77.93 (d, J = 7.0 Hz, CF3).
MS (EI): m/z (%) = 226 (M+, 64), 211 (73), 197 (59), 183 (93), 170
References
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(2) (a) Suzuki, Y.; Hagiwara, T.; Kawamura, I.; Okamura, N.;
Kitazume, T.; Kakimoto, M.; Imai, Y.; Ouchi, Y.; Takezoe,
H.; Fukuda, A. Liq. Cryst. 1989, 6, 167. (b) Mikami, K.
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(77), 115 (33), 97 (83), 81 (70), 71 (100), 55 (74).
HRMS: m/z [M – H]+ calcd for C10H16F3O2: 225.1102; found:
225.1096.
1,1,1-Trifluoro-3-(octyloxy)propan-2-one (4a); Typical Proce-
dure
To a soln of alcohol 1a (188 mg, 0.77 mmol) in CH2Cl2 (0.2 mL)
was added a 15% w/w Dess–Martin reagent in CH2Cl2 (24 mL, 3.68
g, 1.05 mmol). The mixture was stirred at r.t. for 19 h. The resultant
cloudy soln was diluted with Et2O (10 mL), washed with 10% aq
Na2S2O3 (10 mL), sat. NaHCO3 soln, and brine, and dried (MgSO4).
After filtration and concentration, the residual oil was purified by
flash column chromatography (hexane–Et2O, 85:15) to afford 4a
(146 mg, 78%) as a colorless oil. The compound was obtained
mainly as the hydrate form (keto/hydrate, 22:78).
1H NMR (500 MHz, CDCl3): d = 3.60 (t, J = 7 Hz, 2 H), 3.62 (s, 2
H), 3.52 (t, J = 6.5 Hz, 2 H), 1.61 (m, 2 H), 1.27 (br, 12 H), 0.87 (t,
J = 7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 188.70 (q, J = 34.4 Hz, CO),
122.47 (qCF, J = 284 Hz, CF3 keto), 115.28 (qCF, J = 290.6 Hz, CF3
hydrate), 92.33 (qCCF, J = 32.3 Hz, C(OH)2), 72.80, 69.62, 31.77,
29.40, 29.31, 29.18, 25.86, 22.63, 14.07.
(3) Harada, T.; Nakagawa, Y.; Wadkins, R. M.; Potter, P. M.;
Wheelock, C. E. Bioorg. Med. Chem. 2009, 17, 149.
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19F NMR (282 MHz, CDCl3): d = –78.48 (s, COCF3), –85.88 (s,
C(OH)2CF3).
HRMS: m/z [M – H]+ calcd for C11H18F3O2: 239.1252; found:
239.1259.
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1,1,1-Trifluoro-3-[(Z)-tetradec-9-enyloxy]propan-2-one (4e)
Following a similar procedure starting from alcohol 1e, with col-
umn chromatography purification (silica gel) gave TFMK 4e (81%
isolated yield). The chemical was obtained mainly in its hydrate
form (keto/hydrate 20:80).
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Synthesis 2010, No. 18, 3117–3120 © Thieme Stuttgart · New York