Organic Process Research & Development
Article
°C and washed with H2O (40 mL) at the same temperature to
keep NaBr dissolved. Then, the mixture was further washed
successively with 5% aq Na2SO3 (40 mL), 5% NaHCO3 (40
mL), and H2O (40 mL) at 25−30 °C. The organic phase was
separated and evaporated to provide crude 4 as a light-yellow
oil [48.4 g (content: 89.3%), assay yield: 88%]. The crude
product was used as is in the next reaction. An analytically pure
sample of 4 was obtained by distillation (bp 85−87 °C/3
TMSI obtained was given by the following procedure: under a
N2 atmosphere, to a mixture of TMSCl (1.0 g, 9.2 mmol) and
TBAB (148 mg, 0.46 mmol) in CD2Cl2 (5.0 mL) were added
NaI (1.66 g, 11 mmol) and mesitylene (1.11 g, 9.2 mmol) and
the mixture was stirred at 40 °C for 1 h. An aliquot (700 μL)
1
of the mixture was allowed for H NMR (CD2Cl2, 400 MHz)
yield of 7 (90.0%) by comparing integration of signals for the
methyl group of TMSI and mesitylene. 7: 1H NMR (400 MHz,
1
mmHg). H NMR (400 MHz, CDCl3): δ 4.09 (t, J = 7.6 Hz,
1
CD2Cl2): δ 0.55 (9H, s). Mesitylene: H NMR (400 MHz,
2H), 3.05−3.12 (m, 2H), 2.22−2.30 (m, 2H), 1.62−1.85 (m,
4H), 1.21 (t, J = 7.6 Hz, 3H). Conditions for GC analysis:
column: HP-5 (30 m × 0.32 mm × 0.25 μm), column
temperature: 100−280 °C, 10 °C/min, injection temperature:
300 °C, injection volume: 0.2 μL, detector: FID, detection
temperature: 300 °C, carrier gas: He (1.1 mL/min), split: 60:1.
Ethyl 5-Iodopentanoate (4) (under Microwave Irradi-
ation).9 To a solution of ethyl 5-bromopentanoate 3 (1 g, 4.78
mmol) and nBu4NBr (77.1 mg, 0.239 mmol) in toluene (5
mL) were added NaI (860 mg, 5.74 mmol) and H2O (50 μL)
at 25 °C, and the mixture was stirred under microwave
irradiation (5−10 W, 1−2 bar) at 100 °C for 15 min to give 4
in a 99.6% conversion (GC analysis).
CD2Cl2): δ 6.89 (s, 3H), 2.38 (s, 9H). 6: 1H NMR (400 MHz,
CD2Cl2): δ 0.22 (9H, s). Conditions for GC analysis: column:
HP-5 (30 m × 0.32 mm × 0.25 μm), column temperature:
40−230 °C, 10 °C/min, injection temperature: 250 °C,
injection volume: 0.2 μL, detection: FID, detection temper-
ature: 300 °C, carrier gas: He (13.3 mL/min), split: 30:1.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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sı
1H NMR spectra of the products (PDF)
Ethyl (3aS, 4Z, 6aR)-5-{Hexahydro-1,3-dibenzyl-2-
oxo-4H-thieno[3,4-d]imidazol-4-ylidene}pentanoate
(5).9 Under a N2 atmosphere, zinc dust (29.6 g, 363 mmol)
was suspended in a mixture of THF (48 mL) and toluene (34
mL) and Br2 (15.1 g, 94.5 mmol) was added dropwise at 25−
30 °C over 3.5 h. Then, 4 [48.4 g (content: 89.3%), 189
mmol] was added dropwise at 55 °C over 1.5 h. The mixture
was stirred at 55 °C for 3 h. After completion of the reaction (a
98.6% conversion, GC analysis), toluene (97 mL) and 2 (45.1
g, 133 mmol), followed by 10% Pd/C (dry, 1.24 g, 1.17 mmol)
in dimethylformamide (12 mL), were added at 26−42 °C. The
mixture was stirred at 40 °C for 3 h and at 25 °C for 15 h.
After completion of the reaction, 16% aq HCl (108 mL) was
added at 25 °C and the mixture was stirred at the same
temperature for 1 h and filtered. The organic phase was washed
successively with H2O (93 mL, 2 × 165 mL), 5% aq Na2SO3
(165 mL), 10% NaHCO3 (165 mL), and H2O (93 mL) and
evaporated. The residue was co-evaporated with toluene (2 ×
80 mL) to give 5 as a light-yellow syrup (NET 54.4 g, assay
yield: 90.7%). The crude product was used as is in the next
reaction. An analytical sample of 5 was obtained by purification
by silica gel column chromatography (hexane/AcOEt = 5:2).
1H NMR (400 MHz, CDCl3): δ 7.23−7.34 (m, 10H), 5.40−
5.43 (m, 1H), 4.92−4.95 (m, 2H), 4.78−4.82 (m, 1H), 4.05−
4.28 (m, 6H), 2.91−2.96 (m, 2H), 2.24−2.28 (m, 2H), 2.00−
2.18 (m, 2H), 1.60−1.72 (m, 2H), 1.22−1.26 (m, 3H).
Conditions for GC analysis: column: HP-5 (30 m × 0.32 mm
× 0.25 μm), column temperature: 100−280 °C, 10 °C/min,
injection temperature: 300 °C, injection volume: 0.2 μL,
detector: FID, detection temperature: 300 °C, carrier gas: He
(1.1 mL/min), split: 60:1. Conditions for HPLC analysis:
column: L-column ODS, column temperature: 40 °C, injection
volume: 10 μL, 0.01 M KH2PO4 (pH = 3.0) buffer/CH3CN =
50:50, flow rate: 1.0 mL/min.
AUTHOR INFORMATION
Corresponding Author
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Masahiko Seki − New Business Promotion Department,
Tokuyama Corporation, Tsukuba, Ibaraki 300-4247, Japan;
Author
Yusuke Takahashi − New Business Promotion Department,
Tokuyama Corporation, Tsukuba, Ibaraki 300-4247, Japan
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
REFERENCES
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(1) For example, see: (a) Liu, Q.; Dong, X.; Li, J.; Xiao, J.; Dong, Y.;
ACS Catal. 2015, 5, 6111−6137. (b) Hofmayer, M. S.; Hammann, J.
Alkyl Iodides. Org. Lett. 2016, 18, 6456−6459. (c) Shen, Y.; Cornella,
2017, 7, 409−412. (d) Kiyokawa, K.; Watanabe, T.; Fra, L.; Kojima,
11, 3268−3292.
(2) For example, see: (a) Seki, M.; Hatsuda, M.; Mori, Y.; Yoshida,
Kato, D.; Nagae, H.; Tsurugi, H.; Seki, M.; Mashima, K. Syntheses of
Chem. Ger. 1910, 43, 1528−1532. (b) Miller, J. A.; Nunn, M. J.
Trimethylsilyl Iodide (7). Under a N2 atmosphere, to a
mixture of 6 (1.0 g, 9.21 mmol) and TBAB (148 mg, 0.46
mmol) in CH2Cl2 (5.0 mL) was added NaI (1.66 g, 11.1
mmol, 1.2 equiv) and the mixture was stirred at 40 °C for 1 h.
An aliquot (100 μL) of the mixture was dissolved in CH2Cl2
(400 μL) and subjected to GC analysis, and the conversion of
the reaction was determined to be 95.4%. The assay yield of
D
Org. Process Res. Dev. XXXX, XXX, XXX−XXX