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Product Details of 1-Boc-L-azetidine-2-carboxylic acid

CAS No. :51077-14-6
Formula : C9H15NO4
M.W : 201.22
SMILES Code : O=C([C@H]1N(C(OC(C)(C)C)=O)CC1)O
MDL No. :MFCD01321011
InChI Key :JWJVSDZKYYXDDN-LURJTMIESA-N
Pubchem ID :2734495

Safety of 1-Boc-L-azetidine-2-carboxylic acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 1-Boc-L-azetidine-2-carboxylic acid

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 51077-14-6 ]

[ 51077-14-6 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 24424-99-5 ]
  • [ 2133-34-8 ]
  • [ 51077-14-6 ]
YieldReaction ConditionsOperation in experiment
100% Example 15 (S)-1-(tert-Butoxycarbonyl)azetidine-2-carboxylic Acid (13). To a solution of (S)-2-azetidinecarboxylic acid 12 (1.0 g, 10.0 mmol) and di-tert-butyl dicarbonate (2.83 g, 12.5 mmol) in ethanol (20 mL) and water (10 mL) was added NaOH (420 mg, 10.5 mmol) at 0 C. The mixture was stirred overnight at ambient temperature. After evaporation of the ethanol, water (20 mL) was added, then acidified with diluted HCl to a pH of 3 and extracted with ethyl acetate (50 mL*3). The combined ethyl acetate was washed with water (30 mL) and saturated NaCl (30 mL), and dried over Na2 SO4. After evaporation of the ethyl acetate to afford 1.98 g (100%) of 13 as a white solid. 1H NMR (300 MHz, CDCl3) delta 4.79 (m, 1H), 3.93 (m, 2H), 2.46 (m, 2H), 1.48 (s, 9H).
With tetramethyl ammoniumhydroxide; In acetonitrile; at 25℃; for 77h; (a) (S)-1-(tert-Butyloxycarbonyl)azetidine-2-carboxylic acid.; A mixture of <strong>[2133-34-8]L-azetidine-2-carboxylic acid</strong> (1.0 g, 9.9 mmol, Toronto Research), tetramethylammonium hydroxide pentahydrate (2.0 g, 11 mmol, Aldrich) and di-tert-butyl dicarbonate (3.2 g, 15 mmol, Aldrich) in acetonitrile (50 mL) was stirred for 3 d at 25 C. Additional amount of di-tert-butyl dicarbonate (1.0 g, 4.6 mmol) was added and the mixture was stirred for 5 h at 25 C. The reaction mixture was evaporated under reduced pressure and the residue was partitioned between aqueous solution of K2CO3 and 1:1 mixture of EtOAc/hexane. The aqueous phase was separated, acidified with aqueous solution of citric acid, and extracted with EtOAc (3×). The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was dried under vacuo to afford the title compound as a white solid. MS (ESI, neg. ion.) m/z: 200 (M-1).
With 4-methyl-morpholine; sodium hydrogencarbonate; In 1,4-dioxane; water; 7a. 1-t-butyloxycarbonyl-2-(S)-azetidinecarboxylic acid To an ice cooled solution of 2-(S)-azetidinecarboxylic acid (10.15 g, 100.39 mmol) in 1,4 dioxane:water (300 mL, 1:1) was added di-tert-butyl dicarbonate (28.48 g, 130.51 mmol), followed by 4-methylmorpholine (11.68 g, 115.45 mmol). The reaction mixture continued to stir 18 hours, gradually warming to room temperature. The reaction mixture was then poured into a ice cooled saturated solution of sodium bicarbonate (250 mL) and washed with ethyl acetate (3*250 ml). The aqueous was then acidified with potassium hydrogen sulfate (pH=1) and the product extracted with ethyl acetate (3*300 ml). These extracts were then dried (Na2 SO4), filtered and concentrated in vacuo. The resulting semisolid was carried forward without further purification. MS (DCI/NH3) m/e 202 (M+H)+, 219 (M+NH4)+. 1 H NMR (CDCl3, 300 MHz) delta: 10.0 (br s, 1H), 4.81-4.76 (t, J=15 Hz, 1H), 3.99-3.83 (m, 2H), 2.62-2.38 (m, 2H), 1.48 (s, 9H).
To a mixture of (S)-(-)-2-azetidinecarboxylic acid (110 mg, 1.1 mmol), Boc2O (290 mg, 1.30 mmol), and DMAP (0.017 g, 0.14 mmol) in 4:1 DMF/H2O (10 mL) is added Et3N (0.30 mL, 2.2 mmol). The reaction mixture is stirred at rt for 68 h, and then is concentrated. The concentrate is diluted with EtOAc, and the EtOAc solution is washed with cold 10% KHSO4. The combined organic extracts are dried, filtered and concentrated to give the title compound as a colorless oil: TLC (750:250:1 Hexanes/acetone/HCO2H) Rf=0.26; 1H NMR (CD3OD) delta 4.97 (1H), 4.57 (1H), 3.98 (1H), 3.87 (1H), 2.57 (H), 2.13 (1H), 1.42 (9H); MS (-ESI) m/z 200.3.

  • 2
  • [ 58632-95-4 ]
  • [ 2133-34-8 ]
  • [ 51077-14-6 ]
  • 3
  • tert-butyl S-4,6-dimethylpirimidin-2-ylthiocarbonate [ No CAS ]
  • [ 2133-34-8 ]
  • [ 51077-14-6 ]
  • 4
  • [ 51077-14-6 ]
  • [ 161511-85-9 ]
YieldReaction ConditionsOperation in experiment
100% Example 16 (S)-tert-Butyl 2-(Hydroxymethyl)azetidine-1-carboxylate (14).17 To a solution of 13 (0.94 g, 4.7 mmol) in THF (10 mL) was added slowly a 1 M BH3 in THF (21.0 mL) at 0 C. The mixture was stirred 2 days at ambient temperature, then cold water (20 mL) was added at 0 C. After evaporation of the THF in vacuo, an 10% aqueous solution of citric acid (15 mL) was added and extracted with ethyl acetate (50 mL*2). The combined ethyl acetate was washed with saturated NaHCO3 (30 mL) and NaCl (30 mL), and dried over Na2SO4. Evaporation of the ethyl acetate in vacuo afforded 0.86 g (100%) of 14 as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 4.40 (m, 1), 3.85-3.70 (m, 3H), 2.13 (m, 1H), 1.90 (m, 1H), 1.42 (s, 9H).
87% With boron dimethyl-trifluoro sulphide; In tetrahydrofuran; at 0℃; for 2h;Heating / reflux; (S)-1-(tert-butoxycarbonyl)-2-azetidinecarboxylic acid (10.42 g, 49.4mmol) was introduced into a 500-mLpear-shaped flask, and tetrahydrofuran (200 mL) was added to dissolve the compound. Then, a tetrahydrofuran solution of 10 M borane-dimethyl sulfide complex salt (9.87 mL, 98.7 mmol) was slowly added at 0C, and the mixture was heated to reflux for 2 hours while stirring. The reaction solution was left to cool, and then was concentrated under reduced pressure. Ice water (100 mL) was poured thereto, and the mixture was extracted with ethyl acetate (200 mLx2). The extract was washed with saturated brine (200 mL), and then dried over anhydrous sodium sulfate. After filtering the extract, the filtrate was concentrated under reduced pressure to obtain the title compound (8.03 g, 42.9mmol, 87%) as an oily matter. NMR(CDCl3)δ:1.45(9H,s),1.93(1H,brs),2.13-2.22(1H,m),3.67-3.81(3H,m),3.87(1H,q,J=8.8Hz),4.21(1H,br s),4.44(1H,br s). MS(ESI)m/z:188(M++1).
With sodium tetrahydroborate; iodine; In tetrahydrofuran; at 0℃; for 19.5h;Reflux; Inert atmosphere; To 699 mg (18.48 mmol) sodium borohydride in 20 mL dry THF under nitrogen, was added 1.15 g (5.74 mmol) (S)-azetidine-1 ,2-dicarboxylic acid 1 -te/f-butyl ester and the reaction was cooled to 0 C, 1.72 g (6.78 mmol) iodine in 10 mL dry THF was added dropwise over 30 minutes, the reaction mixture was allowed to warm to room temperature, and was heated under reflux for 19 hours. The mixture was cooled to room temperature and 25 mL MeOH was added dropwise over 15 minutes. After evaporation of the solvent, 30 mL KOH (1 M) was added and the mixture was stirred at room temperature for 2 hours. The aqueous phase was extracted with DCM (2 x 75 mL) and the combined organic layers were washed with saturated brine (3 x 50 mL), then dried over MgSO4. After filtration, the solvent was evaporated to give the desired product, which was used for the next step without further purification.
  • 5
  • [ 2133-34-8 ]
  • [ 51077-14-6 ]
YieldReaction ConditionsOperation in experiment
55% EXAMPLE 3 Methanol (40mL) was added to the (R)-4-phthalimido-2-chlorobutyric acid (5 g) and the mixture was stirred. To the mixture 80% hydrazine hydrate (2.3 g) was added with stirring, and the mixture was stirred at 40C overnight. Water (30 mL) was then added to the mixture with stirring, and 47% sulfuric acid (13 mL) was added. The mixture was stirred at room temperature for 4 hours and the precipitate was filtered out. The filtrate was concentrated under reduced pressure to recover an aqueous solution of (R)-4-amino-2-chlorobutyric acid. A small amount of the solution was sampled to identify the molecular structure by NMR. The analytical data was as follows:1H-NMR (D2O): delta 2.15-2.45 (m,2H), 3.19 (t,2H), 4.45 (t, 1H) The solution was then placed in an ice bath and an aqueous sodium hydroxide solution (400 g/L) was added to the solution in order to adjust the pH of the solution to 2.0. Water was added to the solution to obtain about 130 g of solution. The resultant solution was heated to about 90C with stirring. Magnesium hydroxide (1.0 g) was added to the solution and the solution was stirred for 5 hours to produce an aqueous solution of (S)-azetidine-2-carboxylic acid. A small amount of the solution was sampled to identify the molecular structure by NMR. The analytical data was as follows: 1H-NMR (CD3OD): delta 2.15 (m,1H), 2.58 (m,1H), 3.90 (m,1H), 4.02 (q,1H), 4.60 (t,1H) The solution was spontaneously cooled to room temperature. Sodium carbonate (2.1 g) and DIBOC (4.3 g) were added with stirring and the mixture was further stirred overnight. Hydrochloric acid (6N) was added to the solution in order to adjust the pH of the solution to 2.0. The resultant solution was extracted with ethyl acetate three times. The resultant organic solution was washed with a saturated brine solution and dried with sodium sulfate. The solvent in the mixture was then removed to recover (S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (2.1 g) (yield 55%, optical purity 89.3 %e.e.). A small amount of the solution was sampled to identify the molecular structure by NMR. The analytical data was as follows:1H-NMR (CDCl3): delta 1.48 (s,9H), 2.40-2.60 (bs,2H), 3.80-4.00 (bs,2H), 4.80 (t,1H)
41% EXAMPLE 4 Dioxane (3 mL) was added to (S)-4-phthalimido-2-hydroxybutyric acid (1.0 g) in a nitrogen atmosphere. Thionyl chloride (2.5 g) was added to the mixture with stirring, and the mixture was stirred at 40C for one hour. Pyridine (0.06 g) was then added to the mixture and further stirred at 40C for 15 hours to produce a solution of dioxane and (R)-4-phthalimido-2-chlorobutyryl chloride. The solution was placed in an ice bath and then water (5 mL) was added with stirring. The solution was extracted with ethyl acetate at room temperature. The resultant organic solution was washed with a brine solution and was dried with mirabilite. The resultant solution containing ethyl acetate was concentrated under reduced pressure to recover (R)-4-phthalimido-2-chlorobutyric acid. Methanol (9 mL) was added to the compound. To the mixture 80% hydrazine hydrate (0.5 g) was added with stirring, and the mixture was stirred at 40C overnight. Water (6 mL) was then added to the solution with stirring and 47% sulfuric acid (3 mL) was added to the solution. The mixture was stirred at room temperature for three hours and the precipitate was filtered. The filtrate was concentrated under reduced pressure to produce an aqueous solution of (R)-4-amino-2-chlorobutyric acid. The solution was then placed in an ice bath and an aqueous sodium hydroxide solution (400 g/L) was added to the solution in order to adjust the pH of the solution to 2.0. Water was added to the solution to obtain about 30 g of solution. The resultant solution was heated to about 80C with stirring. Magnesium hydroxide (0.20 g) was added to the solution and the solution was stirred for 10 hours to produce an aqueous solution of (S)-azetidine-2-carboxylic acid. The solution was spontaneously cooled to room temperature. Sodium carbonate (0.43 g) and DIBOC (0.90 g) were added with stirring and the mixture was further stirred overnight. Hydrochloric acid (6N) was added to the solution in order to adjust the pH of the solution to 2.0. The resultant mixture was extracted with ethyl acetate three times. The resultant organic solution was washed with a saturated brine solution and dried with sodium sulfate. The solvent in the mixture was then removed to recover (S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (0.32 g) (yield 41%, optical purity 87.1 %e.e.).
  • 6
  • [ 109-02-4 ]
  • [ 24424-99-5 ]
  • [ 2133-34-8 ]
  • [ 51077-14-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In 1,4-dioxane; water; 7a. 1-t-butyloxycarbonyl-2-(S)-azetidinecarboxylic acid To an ice cooled solution of 2-(S)-azetidinecarboxylic acid (10.15 g, 100.39 mmol) in 1, 4 dioxane:water (300 mL, 1:1) was added di-tert-butyl dicarbonate (28.48 g, 130.51 mmol), followed by 4methylmorpholine (11.68 g, 115.45 mmol). The reaction mixture continued to stir 18 hours, gradually warming to room temperature. The reaction mixture was then poured into a ice cooled saturated solution of sodium bicarbonate (250 mL) and washed with ethyl acetate (3*250 ml). The aqueous was then acidified with potassium hydrogen sulfate (pH=1) and the product extracted with ethyl acetate (3*300 ml). These extracts were then dried (Na2 SO4), filtered and concentrated in vacuo. The resulting semisolid was carried forward without further purification. MS (DCI/NH3) m/e 202 (M+H)+, 219 (M+NH4)+. 1 H NMR (CDCl3,300 MHz) delta: 10.0 (br s, 1H), 4.81-4.76 (t, J=15Hz, 1H), 3.99-3.83 (m, 2H), 2.62-2.38 (m, 2H), 1.48 (s, 9H).
  • 7
  • [ 161511-85-9 ]
  • [ 51077-14-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hypochlorite; sodium bicarbonate; sulfuric acid; cyfluthrin; sodium thiosulfate; sodium bromide; In water; ethyl acetate; EXAMPLE 10 Synthesis of (S)-N-t-butoxycarbonylazetidine-2-carboxylic Acid STR15 A reaction flask was charged with the (S)-N-t-butoxycarbonylazetidine-2-methanol (2.97 g, 15.9 mmol) obtained in Example 5, TEMPO (25.0 mg, 0.159 mmol), NaBr (4.94 g, 47.7 mmol), ethyl acetate (35 mL) and water (7 mL). Thereto was added, at 5 to 10 C., a mixture of an aqueous solution of sodium hypochlorite (Nakalai Tesque, 80 mL) and sodium hydrogen carbonate (4.68 g, 55.7 mmol). Stirring was further continued for 3 hours. Sodium thiosulfate (0.79 g, 5.06 mmol) was added to the reaction mixture, and the mixture was stirred for 5 minutes. Then, the reaction mixture was adjusted to pH 2 by adding 10% sulfuric acid and extracted with ethyl acetate (50 mL*2), the organic layer was washed with water (50 mL*2), dried over magnesium sulfate and filtered, and the filtrate was concentrated to give white crystals (3.18 g).
 

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