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Chemical Structure| 130369-04-9

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Product Details of [ 130369-04-9 ]

CAS No. :130369-04-9
Formula : C10H17NO2
M.W : 183.25
SMILES Code : O=C(OC(C)(C)C)NC1CC(C1)=C
MDL No. :MFCD09991757

Safety of [ 130369-04-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 130369-04-9 ]

* 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 [ 130369-04-9 ]

[ 130369-04-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 24424-99-5 ]
  • [ 15760-36-8 ]
  • [ 130369-04-9 ]
YieldReaction ConditionsOperation in experiment
39.4% N-Boc-S-Methylene-cyclobutanainineTo a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. BoC2O (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45 C overnight. The reaction was then cooled to 0C and was quenched with 10% aq. NaNO2 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHCO3 (2 x 20 mL), brine (30 ml), dried over Na2SO4, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
34.9% With sodium azide; tetrabutylammomium bromide; zinc trifluoromethanesulfonate; In tetrahydrofuran; at 40 - 45℃; N-Boc-S-Methylene-cyclobutanamineTo a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. BoC2O (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45C overnight. The reaction was then cooled to 00C and was quenched with 10% aq. NaNO2 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHCO3 (2 x 20 mL), brine (30 ml), dried over Na2SO4, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3 -methyl ene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
34.9% To a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g,8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. BoC2O (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 450C overnight. The reaction was then cooled to 0C and was quenched with 10% aq. NaNO2 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHCO3 (2 x 20 mL), brine (30 ml), dried over Na2SO4, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (S, 9 H).
34.9% To a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g,8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. Boc20 (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45C overnight. The reaction was then cooled to 0C and was quenched with 10% aq. NaN02 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHC03 (2 x 20 mL), brine (30 ml), dried over Na2S04, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
34.9% To a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. Boc20 (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45 C overnight. The reaction was then cooled to 0C and was quenched with 10% aq. NaN02 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHC03 (2 x 20 mL), brine (30 ml), dried over Na2S04, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
34.9% To a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. Boc20 (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45C overnight. The reaction was then cooled to 0C and was quenched with 10% aq. NaN<¾ (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHC03 (2 x 20 mL), brine (30 ml), dried over Na2S04, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): *H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
34.9% N-Boc-S-Methylene-cyclobutanamine; To a stirring solution of 3 -methylene- cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 400C. BoC2O (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45C overnight. The reaction was then cooled to 00C and was quenched with 10% aq. NaNO2 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHCO3 (2 x 20 mL), brine (30 ml), dried over Na2SO4, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3-methylene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
34.9% With sodium azide; tetrabutylammomium bromide; zinc trifluoromethanesulfonate; In tetrahydrofuran; at 40 - 45℃; N-Boc-S-Methylene-cyclobutanamineTo a stirring solution of 3-methylene-cyclobutane carboxylic acid (1.0 g, 8.9 mmol) in THF (90 mL) was added NaN3 (2.0 g, 31.1 mmol), followed by tetrabutyl ammonium bromide (0.48 g, 1.5 mmol) and Zn(OTf)2 (0.1 g, 0.3 mmol), and the reaction mixture was heated to 40C. BoC2O (2.1 g, 9.8 mmol) was then added at once, and the reaction was heated at 45C overnight. The reaction was then cooled to 00C and was quenched with 10% aq. NaNO2 (180 mL). The THF was evaporated and the aqueous layer was extracted with EtOAc (180 mL). The organic layer was washed with 5 % aq. NaHCO3 (2 x 20 mL), brine (30 ml), dried over Na2SO4, filtered and concentrated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes: ethyl acetate: 0-90%) to yield the desired N-Boc-3 -methyl ene- cyclobutanamine (0.57 g, 3.1 mmol, 34.9% yield): 1H NMR (250 MHz, CDC13) δ 4.83 (s, 2 H), 4.79 (bs, 1 H), 4.05-4.23 (m, 1 H), 2.92-3.11 (m, 2 H), 2.50-2.65 (m, 2 H), 1.44 (s, 9 H).
1.0 g (8.9 mmol) of 3 -methyl enecyclobutane carboxylic acid, 2.0 g (31.1 mmol) Of NaN3, 0.48 g (1.5 mmol) of tetrabutyl ammonium bromide, O.lg (0.3 mmol) of Zn(OTf)2 and 90ml of dry THF were added to a 250 mL round bottom flask and warmed to 40 0C. When the reaction mixture reached this temperature, 2.1 g (9.8 mmol) of BoC2O was added at once and allowed to react overnight at 45 0C. The reaction mixture was then cooled in ice bath. 180 mL of 10% NaNO2 solution was added and THF was evaporated off. 180 mL EtOAc was used for extraction and the <n="64"/>organic layer was washed with 5% NaHCO3 (2 x 20 mL) followed by brine (once by 30 ml). Dried organic layer over Na2SO4 and evaporated solvent to get a yellow solid. The product was purified on 40 gram Si column to use hexanes/ethyl acetate as eluent, gradient: 0-90 % for 1 hour to give 0.57 g of 1-(N-Boc amino)-3- methylenecyclobutane.

  • 2
  • [ 15760-36-8 ]
  • [ 130369-04-9 ]
  • 3
  • [ 15760-36-8 ]
  • [ 75-65-0 ]
  • [ 130369-04-9 ]
YieldReaction ConditionsOperation in experiment
77% With diphenyl phosphoryl azide; triethylamine;Reflux; Step 2: Preparation of tert-butyl (3-methylidenecyclobutyl)carbamate To a solution of 3-methylidenecyclobutanecarboxylic acid (132 g, 1.17 mol) and Et3N (178 g, 1.76 mol) in tert-butyl alcohol (1 L) was added dropwise DPPA (574 g, 1.41 mol) and the resulting mixture was refluxed overnight. The mixture was then quenched with water (100 mL). After removal of the tert-butyl alcohol, the residue was treated with sat. NH4Cl (500 mL), and the resulting solid precipitate was collected, washed with sat. NH4Cl and sat. NaHCO3 to give the title compound (165 g, 77% yield) as a white solid.
56% With diphenyl phosphoryl azide; triethylamine; at 85℃; for 17h; Triethylamine (11 .9 mL, 85 mmol) was added to <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (Intermediate 21A) (6.37 g, 56.8 mmol) in tei-butanol (57 mL) at room temperature, followed by diphenyl phosphoryl azide (14.7 mL, 68.2 mmol). The reaction mixture was heated at 85 C under nitrogen for 17 h, quenched with water and concentrated. The residue was taken up in diethyl ether, washed with 10% citric acid followed by saturated sodium bicarbonate,the organic layer dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography, eluting with EtOAc:hexanes (1:9) to give the title compound (6.08 g, 56% yield). 1H NMR (400 MHz, CD3SOCD3) 1 .36 (5, 9 H), 2.54-2.64 (m, 2 H), 2.76-2.86 (m, 2 H), 3.92 (h, J = 8 Hz, I H), 4.76 (p, J = 2 Hz, 2 H), 7.23 (d, J = 7 Hz, I H).
 

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