G
S. J. Mattingly et al.
Paper
Synthesis
1H NMR (600 MHz, D2O): = 4.03–3.97 (m, 1 H), 3.56 (dd, J = 11.7, 3.8
Hz, 1 H), 3.44 (dd, J = 11.9, 7.0 Hz, 1 H), 2.30 (dd, J = 15.1, 5.6 Hz, 1 H),
2.27 (dd, J = 15.1, 8.3 Hz, 1 H).
1H NMR (500 MHz, CDCl3): = 7.31 (d, J = 8.5 Hz, 2 H), 6.90 (d, J = 8.5
Hz, 2 H), 5.11 (s, 2 H), 3.82 (s, 3 H), 3.32–3.27 (m, 1 H), 2.84 (dd, J =
5.0, 5.0 Hz, 1 H), 2.59 (dd, J = 6.3, 6.3 Hz, 2 H), 2.56 (dd, J = 5.0, 2.5 Hz,
1 H).
13C NMR (125 MHz, CDCl3): = 170.2 (C), 159.7 (C), 130.1 (CH), 127.7
(C), 114.0 (CH), 66.5 (CH2), 55.2 (CH3), 47.9 (CH), 46.6 (CH2), 38.1
(CH2).
To the crude sodium salt (theoretical 8.25 mmol) was added DMF (8
mL) and imidazole (1.12 g, 16.5 mmol). The mixture was cooled to
0 °C. Triisopropylsilyl chloride (3.34 g, 17.3 mmol) was added. The
mixture was allowed to come to rt then heated at 50 °C for 1 h. The
mixture was poured into hexanes (50 mL) and H2O (20 mL) was add-
ed. The hexane layer was washed with H2O (2 × 10 mL) and brine (10
mL). The solvent was condensed by rotary evaporation. The interme-
diate product, a bis-protected primary silyl ether and silyl ester, was
purified by silica gel chromatography (gradient elution: 0% hexanes to
15% EtOAc in hexanes) and isolated as a clear, colorless oil (2.284 g,
64%). Rf = 0.55 (EtOAc/hexanes, 1:4, KMnO4 stain).
HRMS (EI): m/z [M]+ calcd for C12H14O4: 222.0892; found: 222.0893.
Funding Information
This work was supported by the Natural Science and Engineering Re-
search Council of Canada (NSERC) and the Dianne and Irving Kipnes
Foundation.()
FTIR (neat): 3477 (br), 2945, 2893, 2868, 1719, 1465, 1123, 883, 681
cm–1
.
1H NMR (600 MHz, CDCl3): = 4.14–4.07 (m, 1 H), 3.74 (dd, J = 9.8, 5.3
Hz, 1 H), 3.69 (dd, J = 9.8, 6.0 Hz, 1 H), 2.94 (d, J = 4.9 Hz, 1 H), 2.62
(dd, J = 16.2, 5.3 Hz, 1 H), 2.57 (dd, J = 16.6, 7.5 Hz, 1 H), 1.31 (sept, J =
7.1 Hz, 3 H), 1.14–1.04 (m, 39 H).
13C NMR (150 MHz, CDCl3): = 172.2 (C), 68.8 (CH), 66.3 (CH2), 39.4
(CH2), 17.9 (CH3), 17.7 (CH3), 11.9 (CH).
Supporting Information
Supporting information for this article is available online at
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HRMS (ESI): m/z [M + Na]+ calcd for C22H48NaO4Si2: 455.2983; found:
References
455.2979.
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Anal. Calcd for C22H48O4Si2: C, 61.06; H, 11.18. Found: C, 61.08; H,
11.11.
(2) (a) Van Hee, V. F.; Grasso, D.; Sonveaux, P.; Labar, D.; Gregoire,
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Following a chemoselective deprotection strategy outlined by Chen et
al.,28 the bis-protected intermediate (1.78 g, 4.11 mmol) was dis-
solved in DMF/H2O (20:1, 21 mL) and heated at 70 °C for 3 h. The reac-
tion was cooled to rt, diluted with Et2O (80 mL), washed with sat.
aqueous NH4Cl (2 × 30 mL) and brine (2 × 30 mL), and dried over
Na2SO4. The solvent was evaporated by rotary evaporation and the
crude residue was purified by silica gel chromatography (hex-
anes/EtOAc, 1:1). The product was isolated as a clear, yellow oil (0.848
g, 75%). Rf = 0.17 (hexanes/EtOAc, 1:1, KMnO4 stain). The 1H NMR was
in agreement with Cooksey et al.30
1H NMR (600 MHz, CDCl3): = 4.17–4.10 (m, 1 H), 3.77 (dd, J = 9.8, 4.5
Hz, 1 H), 3.68 (dd, J = 9.8, 6.0 Hz, 1 H), 2.64 (dd, J = 16.2, 4.5 Hz, 1 H),
2.58 (dd, J = 16.2, 7.9 Hz, 1 H), 1.17–1.09 (m, 3 H), 1.09–1.05 (m, 18 H).
13C NMR (150 MHz, CDCl3): = 177.1 (C), 68.5 (CH), 66.3 (CH2), 37.8
(CH2), 17.9 (CH3), 11.8 (CH).
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p-Methoxybenzyl 3,4-Epoxybutyrate (18d)
p-Methoxybenzyl 3-butenoate (17d) (0.477 g, 2.312 mmol) was dis-
solved in CH2Cl2 (12 mL) and chilled to –78 °C. Reagent grade ≤77%
MCPBA (1.061 g, 4.624 mmol) was added in one portion. The mixture
was stirred for 48 h before being allowed to come to rt. The precipi-
tated solids were removed by filtration. The solution was quenched
with sat. aqueous K2S2O3 (8 mL) and filtered again. The filtrate was
washed with sat. aqueous K2S2O3 (8 mL), H2O (10 mL), and brine (10
mL), dried over Na2SO4, and condensed by rotary evaporation. The
crude residue was purified by silica gel chromatography. The column
was pretreated with 2% Et3N in hexanes/acetone (2:1). The product
was eluted with hexanes/acetone (2:1, isocratic). The product was
isolated as an amber oil (0.355 g, 69%). Rf = 0.37 (hexanes/acetone,
2:1, with a 2% Et3N pretreated plate).
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FTIR (neat): 3003, 2958, 2838, 1735, 1612, 1516, 1303, 1248, 1170,
1032, 823 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H