Method for preparing chiral deuterated methionine by using heavy water as deuterium source
A technology of deuterated methionine and methionine ester, which is applied in the field of preparation of chiral deuterated methionine, can solve the problems of complex synthesis steps, harsh synthesis conditions, failure to meet application value and market value, and achieve high atom economy and simple operation Effect
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Embodiment 1
[0027] In a water-free and oxygen-free glove box under an argon atmosphere, the Pd(OAc) 2 (0.001 mmol), ( R , R )-PhBox (0.0012 mmol), AgOTf (0.002 mmol), Fe (0.6 mmol) and α - Add dehydroamino acid ester (0.2 mmol) to a 10 mL reaction tube in turn, then add 2 ml DCE (1,2-dichloroethane), then add heavy water (0.4 mmol) and send it out of the glove box. Reaction in 60°C oil bath, TLC monitoring and I 2 Chromogenic detection reaction, after the reaction is completed, concentrate, and pass through the column with silica gel to obtain a white solid, namely chiral N-(tert-butoxycarbonyl)-methioninate, with a yield of 95%. ee The value is 98%, and the deuterium incorporation rate is 96%. 1 H NMR (400 MHz, CDCl 3 ): δH = 1.32 (9H, s), 1.82 (0.1H, dq), 1.93-2.06(4H, m), 2.42 (2H, t), 3.63 (3H, s), 4.29 (0.1H, m), 5.27 (1H, d). 13C NMR (100 MHz, CDCl3): δC = 15.3, 28.2, 29.9, 31.9, 52.2, 52.6, 79.7, 155.3, 172.7.
[0028] Add the above white solid to a round bottom flask, add ...
Embodiment 2
[0030] In a water-free and oxygen-free glove box under an argon atmosphere, [RhCl(COD)] 2 (0.002 mmol), ( R )-Seghos (0.0024 mmol), HB (C 6 f 5 ) 3 (0.01mmol), S 8 (0.1 mmol) and α - Dehydroamino acid esters (0.1 mmol) were sequentially added to a 10 mL reaction tube, then 2 ml tetrahydrofuran was added, and heavy water (0.1 mmol) was added and sent out of the glove box. Reaction in -50°C oil bath, TLC monitoring and I2 The reaction was detected by color development. After the reaction was completed, it was concentrated and passed through a column with silica gel to obtain a white solid. The yield is 20%, ee The value is 88%, and the deuterium incorporation rate is 85%. 1 H NMR (400 MHz, CDCl 3 ): δH = 1.32(9H, s), 1.82 (0.15H, dq), 1.93-2.06 (4H, m), 2.42 (2H, t), 3.63 (3H, s), 4.29 (0.15H, m), 5.27 (1H, d). 13C NMR (100 MHz, CDCl3): δC = 15.3, 28.2, 29.9, 31.9, 52.2, 52.6, 79.7, 155.3, 172.7.
[0031] Step 2: Add the above white solid to a round bottom flask, ad...
Embodiment 3
[0033] Step 1: Ni(OTf) 2 (0.01 mmol), ( R )-Binap (0.012 mmol), B (C 6 f 5 ) 3 (0.2 mmol), H 2 S (0.8mmol) and α - Dehydroamino acid esters (0.3 mmol) were sequentially added to a 10 mL reaction tube, then 2 ml tetrahydrofuran was added, and then water (0.8 mmol) was added and sent out of the glove box. Reaction in 80°C oil bath, TLC monitoring and I 2 The reaction was detected by color development. After the reaction was completed, it was concentrated and passed through a column with silica gel to obtain a white solid. Yield is 75%, ee The value is 88%, and the deuterium incorporation rate is 87%. 1 H NMR (400 MHz, CDCl 3 ): δH = 1.32 (9H,s), 1.82 (0.13H, dq), 1.93-2.06 (4H, m), 2.42 (2H, t), 3.63 (3H, s), 4.29(0.13H, m), 5.27 (1H, d). 13C NMR (100 MHz, CDCl3): δC = 15.3, 28.2, 29.9, 31.9, 52.2, 52.6, 79.7, 155.3, 172.7.
[0034] Step 2: Add the above white solid to a round bottom flask, add a mixed solvent of TFA (1.8 mL) and dichloromethane (2 mL), stir at room...
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