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Chemical Structure| 71461-30-8 Chemical Structure| 71461-30-8

Structure of 71461-30-8

Chemical Structure| 71461-30-8

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Product Details of [ 71461-30-8 ]

CAS No. :71461-30-8
Formula : C13H15NO3
M.W : 233.26
SMILES Code : O=C(N1[C@H](C=O)CCC1)OCC2=CC=CC=C2
MDL No. :MFCD17214732
InChI Key :ASNHSGGMNWXBEI-LBPRGKRZSA-N
Pubchem ID :11746545

Safety of [ 71461-30-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Application In Synthesis of [ 71461-30-8 ]

* 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 [ 71461-30-8 ]

[ 71461-30-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 6216-63-3 ]
  • [ 71461-30-8 ]
YieldReaction ConditionsOperation in experiment
99% A 100 mL flame-dried Schlenk flask under nitrogen atmosphere was charged with oxalyl chloride (1.64mL, 19.12 mmol, 1.5 eq) and 60 mL dry DCM and cooled to -78 C using dry ice/acetone. DMSO (2.71mL, 38.25 mmol, 3.0 eq) was added dropwise, and the reaction was stirred for 15 min. A solution of 14(3.00 g, 12.75 mmol, 1.0 eq) in 20 mL dry DCM was added dropwise, and the reaction was stirred for 1 h. DIPEA (12 mL) was added, and the reaction was stirred for an additional hour at -78 C, followed by slow warming until the temperature reached -10 C. Saturated aq. NH4Cl was slowly added to quench, and the reaction was brought to room temperature. The organic layer was washed twice with additional saturated aq. NH4Cl, dried over MgSO4, filtered, and evacuated to afford 15 as yellow oil. Cooling in the fridge overnight afforded pale yellow crystals which did not melt upon warming to room temperature. Yield 2.94 g, 99%. [alpha]D25 -24 (c 1 g/100 mL, CH2Cl2). 1H NMR (400 MHz, CDCl3): delta = 9.53 (d, J = 4.0Hz, 1H), 7.34-7.25 (m, 5H), 5.15-5.06 (m, 2H), 4.31-4.10 (m, 1H), 3.57-3.43 (m, 2H), 2.10-1.76 (m, 4H).13C NMR (400 MHz, CDCl3): delta = 199.79, 155.09, 154.23, 136.22, 136.01, 128.25, 127.85, 127.69, 66.97,65.02, 64.62, 47.04, 46.46, 27.49, 26.32, 24.22, 23.43. MS (ESI): m/z calcd for [C13H15NO3 + H]+: 234,found: 234. Spectroscopic data agree with literature.26
90% In a 100 mL two-necked round bottom flask was taken cyanuric chloride (5.65 g, 30.62 mmol, 1.2 equiv), and dissolved in dry THF. To this solution was added dry DMSO (10.86 mL, 153.14 mmol, 6.0 equiv), slowly at -30 C. After 30 min was added Cbz-(S)-prolinol 8 (6.0 g, 25.53 mmol, 1.0 equiv) dissolved in dry THF (60 mL) at -30 C and stirring was continued for further 30 min at -30 C. Et3N (21.32 mL, 153.14 mmol, 6.0 equiv), was added to the reaction mixture and the temperature was maintained for further 30 min at -30 C. Slowly it was allowed to warm-up for room temperature and stirred for further 15 min. The organic solvents were evaporated under reduced pressure to get a white solid. To this was added Et2O and the suspension was treated with 1N HCl till two clear layers develop. The organic layer was separated and treated with saturated solution of NaHCO3, brine and Na2SO4. Flash chromatography using EtOAc: petroleum ether (1:2) afforded a colorless liquid Cbz-(S)-prolinal 9 (5.35 g, 90% yield). [alpha]D -66.58 (c 1.06, CHCl3) (lit. -74.42 (c 0.1384 CHCl3) [23]); IR (Neat): v 3450, 3033, 2955, 2884, 1705, 1415, 1355, 1204, 1173, 1120, 766, 699 cm-1; 1H NMR (200 MHz, CDCl3): delta 1.73-2.27 (m, 4H, CH2), 3.35-3.76 (m, 3H, CH2, CH), 4.10-4.38 (m, 1H, CH), 5.08-5.16 (d, 1H, J = 6.61 Hz, CH), 7.23-7.38 (m, 5H, Ar-H), 9.47 and 9.57 (s, 1H, rotameric CHO). Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C, 66.88; H, 6.42; N, 5.96.
74% With pyridinium chlorochromate; In dichloromethane; at 20℃; for 5h; The solution of (S)-N-benzyloxycarbonyl prolinol 14 (1.97 g, 8.37 mmol) in CH2Cl2 (3 mL) was added to a stirred suspension of pyridinium chlorochromate (2.88 g, 13.39 mmol) in dry CH2Cl2 (30 mL) and the reaction mixture was stirred for 5 h at room temp. Et2O (30 mL) was added and stirred for 20 minute at room temp, and the mixture was filtered through a short bed of celite and the filtrate obtained was evaporated to give a crude product 15, which was passed through a short bed of silica column using EtOAc to give syrupy liquid3 (1.45 g, 74%).
70% With triethylamine; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dimethyl sulfoxide; 24d. N-Cbz-L-prolinal To a stirred solution of N-Cbz-L-prolinol (5 g, 21.26 mmol, from steps 24b or 24c above)in 20 mL of anhydrous DMSO were added 8.89 mL (63.79 mmol) of triethylamine and 10.75 g (63.79 mmol) of SO3 -pyridine complex in 35 mL of DMSO. The reaction mixture was stirred at room temperature for 10 min, then poured into 200 mL of ice water. The mixture was extracted with ether, the extract was dried over Na2 SO4 and concentrated to afford the title product, 3.058 g (70% yield).
70% With triethylamine; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dimethyl sulfoxide; 24d. N-Cbz-L-prolinal To a stirred solution of N-Cbz-L-prolinol (5g, 21.26 mmol, from steps 24b or 24c above) in 20 mL of anhydrous DMSO were added 8.89 mL (63.79 mmol) of triethylamine and 10.75 g (63.79 mmol) of SO3 -pyridine complex in 35 mL of DMSC). The reaction mixture was stirred at room temperature for 10 min, then poured into 200 mL of ice water. The mixture was extracted with ether, the extract was dried over Na2 SO4 and concentrated to afford the title product, 3.058 g (70% yield).
With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -78℃; for 0.583333h; Reference Example 55; L(-)-proline (17.0 g) was dissolved in tetrahydrofuran (350 ml) and a 1 N aqueous sodium hydroxide solution (296 ml), and then benzyl chlorocarbonate (23.2 ml) was added dropwise thereto at 0C under a nitrogen atmosphere. The resulting mixture was returned to room temperature and stirred overnight. 1 N Hydrochloric acid (296 ml) was added thereto at 0C, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give 1-[(benzyloxy)carbonyl]-L-proline, which was as such dissolved in tetrahydrofuran (250 ml), and then triethylamine (26.8 ml) was added thereto. To the resulting solution was added dropwise ethyl chlorocarbonate (16.9 ml) at 0C under a nitrogen atmosphere. The mixture was returned to room temperature and stirred for 1 hour, and the insolubles were removed by filtration. To the filtrate was added dropwise an aqueous sodium borohydride (11.2 g) solution (100 ml) at 0C, and the mixture was returned to room temperature and stirred for 3 hours under a nitrogen atmosphere. Next, water was added thereto, and the mixture was extracted with ethyl acetate twice. The organic layer was washed with saturated brine. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane : ethyl acetate 2 : 1 ? 1 : 4) to give benzyl (2S)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (25.0 g) as a colorless oily material. To a solution of oxalyl chloride (6.23 ml) in dichloromethane (70 ml) was added dropwise a solution of dimethyl sulfoxide (10.9 ml) in dichloromethane (100 ml) at -78C under an argon atmosphere. The mixture was stirred as such for 15 minutes, and then a solution of benzyl (2S)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (12.0 g) in dichloromethane (80 ml) was added dropwise thereto. The mixture was stirred as such for 15 minutes, and then triethylamine (42.7 ml) was added dropwise thereto, followed by stirring as such for 20 minutes. The resulting mixture was returned to room temperature and then water was added thereto, followed by separation. The organic layer was washed with 1 N hydrochloric acid twice, an aqueous 4% sodium carbonate solution and saturated brine, respectively, and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane : ethyl acetate = 2 : 1 ? 1 : 1) to give benzyl (2S)-2-formylpyrrolidine-1-carboxylate. To [2-(1,3-dioxolan-2-yl)ethyl]triphenylphosphonium bromide (90.4 g) was added tetrahydrofuran (400 ml), further added t-butoxypotassium, and the mixture was stirred at room temperature for 1.5 hours under a nitrogen atmosphere. To the resulting mixture was added dropwise a solution of benzyl (2S)-2-formylpyrrolidine-1-carboxylate in tetrahydrofuran (200 ml), and the mixture was stirred at room temperature for 1 hour and at 50C for 3 hours under a nitrogen atmosphere. After returning to room temperature, water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane : ethyl acetate = 3 : 1 ? 2 : 1) to give benzyl (2S)-2-[3-(1,3-dioxolan-2-yl)-1-propenyl]pyrrolidine-1-carboxylate (15.1 g). Benzyl (2S)-2-[3-(1,3-dioxolan-2-yl)-1-propenyl]pyrrolidine-1-carboxylate (15.0 g) was dissolved in ethanol (200 ml), and then 10% palladium carbon (4.0 g, water content: 50%) was added thereto, followed by overnight stirring at room temperature under a hydrogen atmosphere. The insolubles were removed by filtration, and then the solvent was distilled off under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (200 ml) and a 1 N aqueous sodium hydroxide solution (150 ml), and then benzyl chlorocarbonate (10.1 ml) was added dropwise thereto at 0C under a nitrogen atmosphere. The mixture was returned to room temperature, stirred for 3 hours and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane : ethyl acetate = 7 : 1) to give benzyl (2R)-2-[3-(1,3-dioxolan-2-yl)propyl]pyrrolidine-1-carboxylate (13.6 g). Benzyl (2R)-2-[3-(1,3-dioxolan-2-yl)propyl]pyrrolidine-1-carboxylate (13.0 g) was dissolved in tetrahydrofuran (130 ml), and then 2 N hydrochloric acid (305 ml) was added thereto at 0C. After stirring the resulting mixture at room temperature for 3.5 hours, a 1 N aqueous sodium hydroxide solution (610 ml) was added thereto at 0C. The mixture was extracted with ethyl acetate, the organic layer was then washed with satura...

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