A kind of synthetic method of rolipram
A synthesis method and compound technology, which can be used in organic chemistry methods, organic chemistry, bulk chemical production, etc., can solve problems such as expensive transition metal catalysts, and achieve the effects of high stereoselectivity, mild reaction conditions and simple operation.
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Embodiment 1-20
[0045]
[0046] In embodiments 1-20, the alcohol shown in formula II is selected from ethanol, R in formula I and formula III 1 is -Ph, and PG in formula I and formula III is H, Bn or Cbz.
[0047] The structures of NHC A and NHC B in the table below are shown in the following formulas:
[0048]
[0049] The Mes group in the above structure is mesityl. The concrete reaction situation of embodiment 1-20 is as follows:
[0050]
[0051]
[0052] The reaction conditions of Examples 1-20 are as shown above, wherein: the serial number of the embodiment without special identification is the standard reaction conditions, and the conditions are: the alcohol shown in the formula II is selected from ethanol, the R in the formula I and the formula III 1 For -Ph, PG=Cbz formula I compound (0.1mmol), formula II compound (1.5 times molar equivalent), NHC (20mol%), alkali (1.5 times molar equivalent), solvent (0.1M, namely 0.1mol / L ), the reaction temperature is 30℃, N 2 Atmo...
Embodiment 21～35
[0064] Embodiment 21~35 substrate scope of application experiment
[0065]
[0066] In Examples 21-35, the PG substituents are Cbz, R 2 is ethyl, R 1 are selected from different substituents. NHC B is selected as the nitrogen heterocyclic carbene catalyst.
[0067] The product III, yield and ee value of Examples 21-35 are respectively as follows: 3a-3o. The reaction conditions of Examples 21-35 are the same as those of Example 17, and the same yield is the yield after purification by silica chromatography, which is based on the substrate I. The only difference between the examples 21 to 35 is the R in the substrate I 1 Substituents.
[0068]
[0069] 3a is a colorless liquid in the product of the above-mentioned embodiment 21, and its hydrogen spectrogram is as follows figure 1 As shown, the carbon spectrum is shown as figure 2 Shown, the spectrogram result of product 3a is:
[0070] 1 H NMR (400MHz, CDCl 3 )δ7.59 (s, 1H), 7.36 (d, J=4.8Hz, 5H), 7.23-7.29 (m, ...
Embodiment 21
[0073] The high performance liquid phase chromatogram of product 3a in embodiment 21 is as follows Figure 7 Shown, by high performance liquid chromatography [HPLC condition (Chiralcel ODH, 90:10 hexanes / i-PrOH, 1.0mL / min), t r (major) = 50.7min, t r (minor)=33.3min, the ee value of the product is 95%.
[0074] The detection result of product optical rotation is: [α] D 23 (0.03, CHCl 3 )=-296.1;
[0075] The reaction was carried out according to the operating conditions of Example 21, except that the NHC B catalyst was replaced by a racemic catalyst, that is, a mixed catalyst of NHC B and ent NHC B, to obtain racemic product (±)-3a, racemic compound The HPLC of (±)-3a is as follows Figure 6 shown.
[0076] 3j is a colorless liquid in the above product, and its hydrogen spectrum is as follows image 3 As shown, the carbon spectrum is shown as Figure 4 Shown, the spectrogram result of product 3j is:
[0077] 1 H NMR (400MHz, CDCl 3 )δ7.51 (d, J = 7.2Hz, 1H), 7.34-7...
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