(S)-Alpha, Alpha-fluorine-containing diaryl-2-pyrrolidine methanol derivative as well as preparation and applications thereof
A technology of pyrrolidine methanol and derivatives, which is applied in the preparation of organic compounds, carboxylic acid ester preparation, catalyst activation/preparation, etc., and can solve problems such as harsh reaction conditions, expensive catalysts, and environmental pollution
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Examples
Embodiment 1
[0052] Synthesis of Optically Pure (S)-α,α-bis(3,4,5-fluorobenzene)-trimethylsilyl ether 2-pyrrolidine catalyst
[0053] 1. Synthesis of L-proline methyl ester (b)
[0054]
[0055] Add 40mmol (46g) of L-proline (a) and 30mL of methanol to the reaction flask, cool in an ice bath, slowly add 100mmol (118g) of thionyl chloride dropwise while stirring, after dropping, heat and reflux for 6 hours, reduce The solvent was distilled off under pressure to obtain a light yellow oily liquid, which was the crude product (b) of L-proline methyl ester, which was directly used in the next reaction.
[0056] 2. Synthesis of (S)-N-benzyl-2-pyrrolidinecarboxylic acid methyl ester (c)
[0057]
[0058] The crude product (b) from the previous step was dissolved in 40 mL of methanol, 78 mmol (82.6 g) of sodium carbonate was added, 46 mmol (58 g) of benzyl chloride was added dropwise under reflux, and reflux was continued for 4 hours after the dropwise addition. After the reaction was comp...
Embodiment 2
[0072] Other operations are the same as in Example 1, except that in step 4, the protic solvent is changed to isopropanol, and the reaction conditions are as follows.
[0073] Preparation of (S)-α,α-(3,4,5-trifluoro)diphenyl-2-pyrrolidinemethanol (e)
[0074] Take 10 mmol of compound (d) from the previous step, add 0.45 g of 10 wt% palladium carbon, 20 mL of isopropanol, and stir at room temperature under the protection of hydrogen. After reacting for 2 hours, the palladium carbon was removed by filtration, and the solvent was evaporated under reduced pressure to obtain the pure product (S)-α, α-(3,4,5-trifluoro)diphenyl-2-pyrrolidinemethanol (e) 9.3 mmol, the yield is 93%.
Embodiment 3
[0076] Other operations are the same as in Example 1, except that in step 4, the protic solvent is changed to ethanol, and the reaction conditions are as follows.
[0077] (S)--α, α-(3,4,5-trifluoro)diphenyl-2-pyrrolidinemethanol (e) preparation
[0078] Take 10 mmol of compound (d) in the previous step, add 0.45 g of 10 wt% palladium carbon, 40 mL of ethanol, and stir at room temperature under the protection of hydrogen. After reacting for 4 hours, the palladium carbon was removed by filtration, and the solvent was evaporated under reduced pressure to obtain the pure product (S)-α, α-(3,4,5-trifluoro)diphenyl-2-pyrrolidinemethanol (e) 9.6 The mmol yield was 96%.
[0079] Subsequent operations and reaction conditions were the same as in Example 1 to obtain (S)-α,α-bis(3,4,5-fluorobenzene)-trimethylsilyl ether-2-pyrrolidine with a total yield of 38.1%.
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Description
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Application Information
- IPC
- C07F7/18; C07D207/08; C07B53/00; B01J31/02; B01J37/00; C07C67/347; C07C69/738; C07C69/716; C07D311/74; C07D407/04; C07D311/94
- CPC
- Y02P20/55
- Inventors
- 俞传明; 郑飞