546 JOURNAL OF CHEMICAL RESEARCH 2011
Scheme 3
and to the resulting slurry was added 1.0 M n-C4H9MgBr (20 mL,
20 mmol) dropwise at –15 to –5 °C to afford a clear solution. After
cooling to –20 °C again, the Grignard reagent 6 was exchanged above
and added dropwise at 0 °C over 0.5 h.
a cobalt- catalysed coupling reaction, using an efficient
catalytic reagent, CoCl2/TMEDA. This simple protocol will
be very attractive for large scale production. Further studies
are currently underway in our laboratory.
After the completion of the addition, the reaction mixture was
allowed to warm to room temperature over 30 min. and then quenched
with aqueous HCl (1 M, 100 mL). The aqueous layer was extracted
with EtOAc (50 mL × 2), the combined organic layers were washed
with water (100 mL) and dried with MgSO4. Evaporation of the
solvent, then flash chromatography with petroleum ether/ethyl acetate
(5:l) gave 7 as a pale yellow solid (5 g, 14.4 mmol, 72% yield).
[α]D22 = + 14.5 (c 1.0, MeOH). M.p. 76–78 °C. {lit.22 [α]D20 = + 15.2
(c 1.0, MeOH). M.p. 88–88.5 °C.} IR (cm–1): 3360, 2983, 1729, 1688,
1424, 1335, 1250,1029,. 1H NMR (400 MHz, CDCl3) δ 7.17–6.70 (m,
2H), 5.19 (br, 1H), 4.20–4.00 (m, 1H), 3.71 (s, 3H), 2.90–2.81 (m,
2H), 2.58–2.47 (m, 2H), 1.37 (s, 9H). ESI-MS: 348.2 (M + 1)+
Experimental
Melting points were determined with a SGW X-4 micro melting
point apparatus. IR spectra were determined on a Bruker Vertex 70
1
spectrophotometer. H NMR spectra were recorded using an Avance
400 MHz spectrometer. ESI-MS were recorded on a Dionex MSO-
Plus Mass Spectrometer. High resolution mass spectra were recorded
on a Finnigan MAT XL95 mass spectrometer. GC were determined
on a Fuli GC-9790 system. Optical rotations were obtained on a
Perkin-Elmer 241 Autopol polarimeter.
(S)-Methyl [3-(tert-butoxycarbonyl)-amino]-4-hydroxybutanoate
(3): To a mixture of 1 (26.1 g, 0.1 mol) and 1-hydroxypyrrolidine-2,
5-dione (12.7g., 0.11 mol) in ethyl acetate (200 mL), a solution of
DCC (22.7 g, 0.11 mol) in ethyl acetate (50 mL) was added drop-
wise at 0 °C. The mixture was then stirred at r.t. for 8 h and the solvent
was removed under vacuum after being filtered. The formed white
solid and NaBH4 (3.8 g, 0.1 mol) were suspended in THF (200 mL),
methanol (20 mL) was added dropwise at 0 °C. After 0.5 h, sat. NH4Cl
(100 mL) was added, the mixture was stirred for 0.5 h and then
extracted with ethyl acetate (2 × 100 mL). The combined organic
layers were washed with brine, dried, filtered and concentrated to
give the colourless oil 3 (19.6 g, 0.084 mol) in 84% yield over the
two steps. [α]D20 = + 5.9 (c 0.5, CHCl3). {lit23. [α]D23 = + 6.3 (c 0.5,
The authors are grateful to Zhejiang Hisoar Pharmaceutical
Co., Ltd. for financial support.
Received 14 July 2011; accepted 15 September 2011
Paper 1100795 doi: 10.3184/174751911X13155906432537
Published online: 30 September 2011
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