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Chemical Structure| 147081-44-5 Chemical Structure| 147081-44-5
Chemical Structure| 147081-44-5

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Product Details of (S)-1-Boc-3-aminopyrrolidine

CAS No. :147081-44-5
Formula : C9H18N2O2
M.W : 186.25
SMILES Code : N[C@@H]1CN(C(OC(C)(C)C)=O)CC1
MDL No. :MFCD03419271
InChI Key :CMIBWIAICVBURI-ZETCQYMHSA-N
Pubchem ID :854071

Safety of (S)-1-Boc-3-aminopyrrolidine

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H318
Precautionary Statements:P264-P270-P280-P301+P310-P305+P351+P338-P310-P321-P330-P405-P501
Class:6.1
UN#:2810
Packing Group:

Application In Synthesis of (S)-1-Boc-3-aminopyrrolidine

* 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 [ 147081-44-5 ]

[ 147081-44-5 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 24424-99-5 ]
  • [ 79286-79-6 ]
  • [ 99724-19-3 ]
  • [ 147081-44-5 ]
YieldReaction ConditionsOperation in experiment
0.4%; 81.7% With potassium hydroxide; In methanol; at 15 - 20℃; for 1h;pH 11.8 - 12.2; 60 g of methanol and 8.6 g (0.1 mols) of (S)-3-aminopyrrolidine (Chemical purity 99.8 %, optical purity 99.5 % ee - hereinafter referred to as S-AP) were fed into a 200-ml 4-neck flask equipped with a stirrer, a pH sensor and two strapped dropping funnels, and stirred at 15 to 20C. 21.8 g (0.1 mols) of di-tertiary butyl dicarbonate (by Tokyo Chemical) was fed into it via one dropping funnel, and 25 g (0.11 mols) of methanolic solution of 25 % potassium hydroxide was thereinto via the other dropping funnel. With stirring at 15 to 20C, di-tertiary butyl dicarbonate was dropwise added to the reaction system over a period of about 1 hour. During this, the methanolic solution of 25 % potassium hydroxide was dropwise added thereto so as to make the reaction system have a pH of from 11.8 to 12.2. The reaction mixtures were analyzed for its composition, and it comprised 4 % of the starting 3-aminopyrrolidine, 86.7 % of the product, 3-amino-1-tertiary butoxycarbonylpyrrolidine (hereinafter referred to as 1-BocAP), and 8.4 % of 1-tertiary butoxycarbonyl-3-tertiary butoxycarbonylaminopyrrolidine (hereinafter referred to as DiBocAP). After the reaction, the reaction mixtures were concentrated under reduced pressure to make 32 g. 100 g of toluene was added to the concentrated solution, and inorganic salts were precipitated with stirring. The precipitated crystals were filtered away, and the filtrate was distilled under reduced pressure to obtain a fraction at 120 to 125C/0.7 kPa, (S)-3-amino-1-tertiary butoxycarbonylpyrrolidine. Its weight was 15.2 g, and its yield was 81.7 %. (Chemical purity 99.1 %; optical purity 99.5 % ee. ) The positional isomer, 3-tertiary butoxycarbonylaminopyrrolidine was 0.4 %.
  • 2
  • [ 90176-80-0 ]
  • [ 147081-44-5 ]
  • [ 820985-25-9 ]
YieldReaction ConditionsOperation in experiment
1, 1-Dimethylethyl (3S)-3-AMINOPIPERIDINE-1-CARBOXYLATE (5G) and 4-fluoro-2- (trifluoromethyl) benzaldehyde (5. 15G, 26. 8MMOL) were allowed to stir in methanol for 16h at room temperature. Sodium borohydride (1.62g, 26. 8MMOL) was then added portionwise. The resulting solution was further stirred for 2 h at room temperature. The solvent was evaporated in vacuo, water was added, and the solution extracted with dichloromethane. The organic extracts were absorbed onto a methanol washed cationic ion exchange resin (Isolute TM SCX-2). The basic components were recovered from the column by elution with 7N ammonia in methanol. The resultant solution was concentrated in vacuo to yield the desired compound as an oil. This was further purified by column chromatography on silica gel, eluting with ethyl acetate/iso-hexane (0: 100 to 40: 60). The title compound was used in subsequent reactions without further purification. 1H NMR (300 MHz, CDC13) ON : 7.37-7. 28 (m, 2H), 7.24-7. 20 (m, 1H), 3. 80 (s, 2H), 3.52-3. 48 (m, 2H), 3.32 (m, 3H), 3.12 (M, 1H), 2.08-2. 0 (m, 1H), 1.75 (m, 1H), 1.45 (s, 9H).
1, 1-Dimethylethyl (3S)-3-AMINOPIPERIDINE-L-CARBOXYLATE (5G) and 4-fluoro-2- (trifluoromethyl) benzaldehyde (5. 15G, 26. 8MMOL) were allowed to stir in methanol for 16h at room temperature. Sodium borohydride (1.62g, 26.8mmol) was then added portionwise. The resulting solution was further stirred for 2 h at room temperature. The solvent was evaporated in vacuo, water was added, and the solution extracted with dichloromethane. The organic extracts were absorbed onto a methanol washed cationic ion exchange resin (IsoluteTM SCX-2). The basic components were recovered from the column by elution with 7N ammonia in methanol. The resultant solution was concentrated in vacuo to yield the desired compound as an oil. This was further purified by column chromatography on silica gel, eluting with ethyl acetate/iso-hexane (0: 100 to 40: 60). The title compound was used in subsequent reactions without further purification. LH NMR (300 MHz, CDC13) ON : 7.37-7. 28 (m, 2H), 7.24-7. 20 (m, 1H), 3.80 (s, 2H), 3.52-3. 48 (M, 2H), 3.32 (m, 3H), 3.12 (M, 1H), 2.08-2. 0 (m, 1H), 1.75 (m, 1H), 1.45 (s, 9H).
1, 1-Dimethylethyl (3S)-3-aminopiperidine-1-carboxylate (5g) and 4-fluoro-2- (trifluoromethyl) benzaldehyde (5.15g, 26. 8mmol) were allowed to stir in methanol for 16h at room temperature. Sodium borohydride (1.62g, 26. 8mmol) was then added portionwise. The resulting solution was further stirred for 2 h at room temperature. The solvent was evaporated in vacuo, water was added, and the solution extracted with dichloromethane. The organic extracts were absorbed onto a methanol washed cationic ion exchange resin (Isolute SCX-2). The basic components were recovered from the column by elution with 7N ammonia in methanol. The resultant solution was concentrated in vacuo to yield the desired compound as an oil. This was further purified by column chromatography on silica gel, eluting with ethyl acetate/iso-hexane (0: 100 to 40: 60). The title compound was used in subsequent reactions without further purification. 'H NMR (300 MHz, CDC13) 8H : 7.37-7. 28 (m, 2H), 7.24-7. 20 (m, 1H), 3.80 (s, 2H), 3.52-3. 48 (m, 2H), 3.32 (m, 3H), 3.12 (m, 1H), 2. 08-2. 0 (m, 1H), 1.75 (m, 1H), 1.45 (s, 9H).
  • 3
  • [ 156150-67-3 ]
  • [ 147081-44-5 ]
  • [ 915001-95-5 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; ethylene glycol;copper(l) iodide; for 46h;Heating / reflux; To a 50 ml of isopropyl alcohol solution containing 15.0 g of 3 (S) -aminopyrrolidine-1-carboxylic acid tert-butyl ester (80.5 mmol) and 24.8 g of 2-chloro-l-fluoro-4-iodobenzene(96.7 mmol) were added 1.54 g of copper (I) iodide (8.1 mmol),9.0 ml of ethylene glycol (10.1 mmol) and 34.2 g of potassium phosphate (161 mmol) , and heated under reflux under a nitrogen atmosphere for 46 hours. The reaction solution was cooled to room temperature and filtered using Celite. The substance remained in the filter was washed with ethyl acetate and the filtrate was concentrated under reduced pressure together with the washings, and the residue was purified by silica gel column chromatography (n-hexane : ethyl acetate = 4 : 1) . The solvent was distilled off under reduced pressure, and the residue was recrystallized from diethyl ether to thereby obtain 15.9 g of white powdery 3 (S)- (3- chloro-4-fluorophenylamino)pyrrolidine-l-carboxylic acid tert- butyl ester. 1H-NMR(CDCl3) deltappm: 1.47(9H,s), 1.78-1.96 (lH,m) , 2.10-2.28 (IH,m) , 2.10-2.28 (lH,m) , EPO <DP n="69"/>3.11-3.30 (IH,m), 3.30-3.56 (2H,m) , 3.57-3.79 (2H,m) , 3.85- 4.03(lH,m), 6.38-6.47 (IH,m) , 6.60 (IH, dd, J=6. OHz, J=2.9Hz) , 6.90- 7.00 (IH,m) .
  • 4
  • [ 50638-47-6 ]
  • [ 147081-44-5 ]
  • [ 915001-97-7 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 1h;Heating / reflux; To a 5 ml of toluene solution containing 0.20 g of 3 (S) -aminopyrrolidine-1-carboxylic acid tert-butyl ester (1.1 mmol) and 0.238 g of 2-chloro-3-bromoanisole (1.1 mmol) were added 67.0 mg of BINAP (0.11 mmol), 24 mg of tris (dibenzylideneacetone) dipalladium (0.027 mmol) and 144 mg of sodium tert-butoxide (1.5 mmol). The mixture was heated under reflux under a nitrogen atmosphere at 100,C for one hour. After cooling to room temperature, the reaction solution was filtered EPO <DP n="70"/>using Celite. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane : ethyl acetate = 10 : 1 ? 3 : 1) . The purified product was concentrated to dryness under reduced pressure to thereby obtain 0.28 g of light yellow amorphous solid 3 (S) - (3-chloro-4-methoxyphenylamino)pyrrolidine-l-carboxylic acid tert-butyl ester. 1H-NMR(CDCl3) deltappm: 1.47(9H,s), 1.80-1.90 (IH,m) , 2.10-2.20 (lH,m) , 3.10-3.25 (IH,m) , 3.38-3.75(3H,m), 3.83(3H,s), 3.92-3.96 (IH,m) , 6.47 (IH,dd, J=2.8Hz, J=8.8Hz), 6.67 (IH, d, J=2.8Hz) , 6.81 (IH, d, J=8.8Hz) .
  • 5
  • [ 24424-99-5 ]
  • [ 79286-79-6 ]
  • [ 147081-44-5 ]
YieldReaction ConditionsOperation in experiment
In methanol; at 20℃; EXAMPLE 127Preparation of (3'S)-1'-[4-(1H-indol-1-ylmethyl)benzoyl]-1,3'-bipyrrolidine Step 1. A solution of (S)-3-aminopyrrolidine (1 mL, 11.6 mmol) in MeOH at 0 C. is treated with di-tert-butyl dicarbonate [(Boc)2O] (2.5 g, 1 eq), stirred at room temperature overnight and concentrated in vacuo to give a residue.
  • 6
  • [ 24424-99-5 ]
  • [ 103831-11-4 ]
  • [ 147081-44-5 ]
YieldReaction ConditionsOperation in experiment
78% Na2CO3 (5.3 g, 49.9 mmol) was added to a suspension of <strong>[103831-11-4](S)-3-aminopyrrolidine dihydrochloride</strong> (3.61 g, 22.7 mmol) in 60 ml MeOH, and it was stirred for 45 min. Afterwards, the mixture was cooled with an ice bath and Boc2O (4.46 g, 20.4 mmol) in 60 ml MeOH was added dropwise. After stirring for 3 h at 0 C, the solvent was removed under reduced pressure and 60 ml 1 N HCl was added to the residue (pH ~ 2). The aqueous phase was extracted with DCM (1 x) in order to remove double protected (S)-3-aminopyrrolidine. The aqueous phase was made alkaline by addition of solid K2CO3 and was extracted with DCM (3 x). The combined organic phases were dried over Na2SO4 and the solvent was removed under reduced pressure. The title compound was obtained as a colourless oil (1.7 g, 78 % yield). 1H-NMR (300MHz, CDCl3): delta 3.40 - 3.26 (m, 3H), 3.23 - 3.13 (m, 1H), 2.85 (dd, 1H, J = 4.6 Hz, J = 10.3 Hz), 1.85 (dq, 1H, J = 6.0 Hz, 12.3 Hz), 1.52 (ddd, 1H, J = 6.3 Hz, J = 13.6 Hz, J = 20.2 Hz), 1.39 (s, 9H). ES-MS: m/z (%): 187 (100) [MH+], 228 (86) [(MH)+ + MeCN], 373 (30) [2MH+], 172 (21) [(MH)+ + MeCN - C4H8], 131 (20) [MH+ - C4H8].
  • 7
  • [ 60211-57-6 ]
  • [ 530-62-1 ]
  • [ 147081-44-5 ]
  • tert-butyl (S)-3-((((3,5-dichlorobenzyl)oxy)carbonyl)amino)pyrrolidine-1-carboxylate [ No CAS ]
  • 8
  • [ 50638-47-6 ]
  • [ 147081-44-5 ]
  • [ 915001-98-8 ]
 

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