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Chemical Structure| 849203-60-7 Chemical Structure| 849203-60-7

Structure of 849203-60-7

Chemical Structure| 849203-60-7

tert-Butyl 1-oxo-7-azaspiro[3.5]nonane-7-carboxylate

CAS No.: 849203-60-7

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Cat. No.: A612603 Purity: 98%

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Product Details of [ 849203-60-7 ]

CAS No. :849203-60-7
Formula : C13H21NO3
M.W : 239.31
SMILES Code : CC(C)(C)OC(=O)N1CCC2(CCC2=O)CC1
MDL No. :MFCD14585368
InChI Key :IJUALTPNDJIBJT-UHFFFAOYSA-N
Pubchem ID :21983962

Safety of [ 849203-60-7 ]

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

Application In Synthesis of [ 849203-60-7 ]

* 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 [ 849203-60-7 ]

[ 849203-60-7 ] Synthesis Path-Downstream   1~34

  • 1
  • [ 849203-60-7 ]
  • [ 66713-38-0 ]
  • [ 849203-61-8 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; In dichloromethane; water; at 0 - 20℃; for 20h; The <strong>[849203-60-7]tert-butyl 1-oxo-7-azaspiro[3.5]nonane-7-carboxylate</strong> (10.9 mmol) from Step A was taken up in methylene chloride (20 mL) and allyl tetrahydrothiophenium bromide (2.74 g, 13.1 mmol) (prepared from allyl bromide and tetrahydrothiophene in methanol according to J. Chem. Soc., Perkin Trans. I, 1993, 2979) and benzyltriethylammonium chloride (0.25 g, 1.1 mmol) were added. The mixture was cooled in an ice bath while 10N NaOH (17 mL) was added. The reaction was then stirred as it was allowed to warm to room temperature over 20 h. The reaction was diluted with water and extracted three times with methylene chloride. The organic layers were combined, washed with saturated sodium chloride solution, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography eluting with 10% ethyl acetate in hexanes to afford the intermediate spiro cyclobutyl/allyl epoxide (0.5 g) as a mixture of isomers along with starting material (1.74 g). 1H NMR (400 MHz, CDCl3): (partial spectrum) δ 1.464 (s, 9 H), 3.27 and 3.39 (2 d, 1 H), 5.25-5.3 and 5.32-5.36 (2 m, 1 H), 5.4-5.5 (m, 1 H) 5.5-5.56 and 5.58-5.68 (2 m, 1 H).
  • 2
  • [ 849203-59-4 ]
  • [ 849203-60-7 ]
YieldReaction ConditionsOperation in experiment
With lithium tetrafluoroborate; In toluene; at 80℃; for 1.5h; The residue was taken up in toluene (70 mL) and lithium tetrafluoroborate (81 mg, cat.) was added. The mixture was heated to 80 C. for 90 min, cooled, then quenched with water, and extracted three times with ether. The organic layers were combined, washed with saturated sodium chloride solution, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography eluting with 20% ethyl acetate in hexanes to afford the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 0.932 (t, 2 H), 1.071 (t, 2 H), 1.484 (s, 9 H), 1.6-1.8 (m, 2 H), 1.8-1.95 (m, 2 H), 3.45-3.55 (m, 2 H), 3.65-3.75 (m, 2 H).
2.96 g With lithium tetrafluoroborate; In toluene; at 80℃; for 2h; Dried crude t-butyl 10-oxa-7-azadispiro[2.0.5.1]decane-7-carboxylate (6.2 g, 26 mmol) was dissolved in anhydrous toluene (60 mL). To this solution was added lithium tetrafluoroborate (122 mg) in one lot. The mixture was heated to 80 C for 2 h. After cooling to RT, about 50 mL of toluene was removed under reduced pressure. The reaction mixture was then quenched with water (40 mL). The product was extracted with diethyl ether (3 x 50 mL), washed with brine (2 x 60 mL), dried over sodium sulfate and evaporated to dryness. The residue was purified by flash column chromatography on silica gel with ethyl acetate/hexane (20:80) to give tert-butyl 1 -oxo-7-azaspiro[3 , 5] -nonane-7-carboxylate (2.96 g, 12.4 mmol) as a white solid.
  • 3
  • [ 849203-60-7 ]
  • [ 100-46-9 ]
  • [ 1100748-83-1 ]
YieldReaction ConditionsOperation in experiment
85% With sodium tris(acetoxy)borohydride; In 1,2-dichloro-ethane; at 20℃; for 18h; To a solution of tert-butyl 1-oxo-7-azaspiro[3,5]-nonane-7-carboxylate (2.96 g, 12.4 mmol) in anhydrous 1,2-dichloroethane (35 mL) was added benzylamine (1.6 g, 14.9 mmol) followed by sodium triacetoxyborohydride (5.3 g, 24.8 mmol). The mixture was stirred at rt for 18 h and then quenched with saturated aqueous sodium bicarbonate and the product extracted with EtOAc (3 x 50 mL). The combined extracts were washed with water (2 x 40 mL) and brine (2 x 50 mL), dried over Na2 SO4, and concentrated to dryness. The product was purified by silica gel chromatography eluting with 2% MeOHIDCM to give tert-butyl 1 -(benzylamino)-7-azaspiro[3 .5 ]nonane-7-carboxylate (3.48 g, 85%).Mass Spectrum (ESI) m/z = 331.2 (M+H).
  • 4
  • [ 849203-60-7 ]
  • [ 301226-27-7 ]
YieldReaction ConditionsOperation in experiment
46% With dihydrogen peroxide; sodium hydroxide; In tetrahydrofuran; methanol; Intermediate 20 was prepared from <strong>[849203-60-7]tert-butyl 1-oxo-7-azaspiro[3.5]nonane-7-carboxylate</strong> by a Baeyer-Villiger reaction using 30% hydrogen peroxide and 0.5 N sodium hydroxide in THF/MeOH (46%).
  • 5
  • [ 849203-60-7 ]
  • (R)-N-((S)-7-(6-amino-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazin-2-yl)-7-azaspiro[3.5]nonan-1-yl)-2-methylpropane-2-sulfinamide [ No CAS ]
  • 6
  • [ 849203-60-7 ]
  • (S)-7-(6-amino-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazin-2-yl)-7-azaspiro[3.5]nonan-1-amine [ No CAS ]
  • 7
  • [ 849203-60-7 ]
  • (R)-2-methyl-N-((S)-7-azaspiro[3.5]nonan-1-yl)propane-2-sulfinamide [ No CAS ]
  • 8
  • [ 849203-60-7 ]
  • [ 196929-78-9 ]
  • (S)-tert-butyl 1-((R)-1,1-dimethylethylsulfinamido)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
4.79 g A solution of fer?-butyl l-oxo-7-azaspiro[3.5]nonane-7-carboxylate (5.24 g, 21.9 mmol), titanium(IV) isopropoxide (16.2 mL, 54.7 mmol), and (R)-2-methylpropane- 2-sulfinamide (3.45 g, 28.5 mmol) in THF (99 mL) was stirred for 12 h at 65 C. After cooling to -78 C, MeOH (9.9 mL) was added followed by lithium borohydride (1.43 g, 65.7 mmol). The resulting mixture was stirred at -78 C for 3 h and at RT for 1 h. MeOH was slowly added to quench the excess of borohydride followed by addition of brine. The resulting mixture was stirred for 15 min and then filtered through Celite. The aqueous mixture was extracted with EtOAc (3 x 20 mL). The organic phases were dried over MgS04, filtered, and the volatiles were removed under reduced pressure. The resulting residue was purified by silica chromatography (0 to 50% gradient of EtO Ac/heptane to give (5)-?er?-butyl l-((R)-l,l-dimethylethylsulfinamido)-7- azaspiro[3.5]nonane-7-carboxylate (4.79 g. 13.90 mmol) as a white solid. MS m/z 345.3 (M+H)+.
4.79 g A solution of teri-butyl l-oxo-7-azaspiro[3.5]nonane-7-carboxylate (5.24 g, 21.9 mmol), titanium(IV) isopropoxide (16.2 mL, 54.7 mmol), and (R)-2- methylpropane-2-sulfinamide (3.45 g, 28.5 mmol) in THF (99 mL) was stirred for 12 h at 65 C. After cooling to -78 C, MeOH (9.9 mL) was added followed by lithium borohydride (1.43 g, 65.7 mmol). The resulting mixture was stirred at -78 C for 3 h and at room temperature for 1 h. MeOH was slowly added to quench the excess of borohydride followed by addition of brine. The resulting mixture was stirred for 15 min and then filtered through Celite. The aqueous mixture was extracted with EtOAc (3 x 20 mL). The organic phases were dried over MgS04, filtered, and concentrated. The resulting residue was purified by silica chromatography (0-50% EtO Ac/heptane eluent) to provide (5)-teri-butyl 1 -((/?)- 1 , 1- dimethylethylsulfinamido)-7-azaspiro[3.5]nonane-7-carboxylate (4.79 g. 13.90 mmol) as a white solid. LCMS: m/z 345.3 (M+H)+.
4.79 g A solution of <strong>[849203-60-7]tert-butyl 1-oxo-7-azaspiro[3.5]nonane-7-carboxylate</strong> (5.24 g, 21.9 mmol), titanium(IV) isopropoxide (16.2 mE, 54.7 mmol), and (R)-2-methylpro- pane-2-sulfinamide (3.45 g, 28.5 mmol) in THF (99 mE) was stirred for 12 h at 65 C. Afier cooling to -78 C., MeOH (9.9 mE) was added followed by lithium borohydride (1.43 g, 65.7 mmol). The resulting mixture was stirred at-78 C. for 3 h and at RT for 1 h. MeOH was slowly added to quench the excess of borohydride followed by addition of brine. The resulting mixture was stirred for 15 mm and then filtered through Celite. The aqueous mixture was extracted with EtOAc (3x20 mE). The organic phases were dried over Mg504, filtered, and the volatiles were removed under reduced pressure. The resulting residue was purified by silica chromatography (0 to 50% gradient of EtOAc/heptane to give (5)-tert-butyl 1 -((R)- 1,1 -dimethylethylsulfinamido)7-azaspiro[3 .5]nonane-7-carboxylate (4.79 g. 13.90 mmol) as a white solid. MS mlz 345.3 (M+H).
  • 9
  • [ 849203-60-7 ]
  • (S)-7-azaspiro[3.5]nonan-1-amine [ No CAS ]
  • 10
  • [ 849203-60-7 ]
  • (R)-N-((S)-7-(6-amino-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazin-2-yl)-7-azaspiro[3.5]nonan-1-yl)-2-methylpropane-2-sulfinamide [ No CAS ]
  • 11
  • [ 849203-60-7 ]
  • (R)-2-methyl-N-((S)-7-azaspiro[3.5]nonan-1-yl)propane-2-sulfinamide [ No CAS ]
  • 12
  • [ 849203-60-7 ]
  • N-(7-azaspiro[3.5]nonan-1-yl)benzamide [ No CAS ]
  • 13
  • [ 849203-60-7 ]
  • N-(7-isobutyl-7-azaspiro [3.5]nonan-1-yl)benzamide [ No CAS ]
  • 14
  • [ 79099-07-3 ]
  • [ 116808-70-9 ]
  • [ 849203-60-7 ]
YieldReaction ConditionsOperation in experiment
75% Thirty grams (0.083 mol) of cyclopropyldiphenylsulfonium triflate was dissolved in 300 mL of anhydrous tetrahydrofuran,Cooled to -40 ,Then, 91 mL of potassium bis (trimethylsilyl) amide at a concentration of 1 M was added dropwise thereto;After the addition is complete and continue stirring for 5 minutes,Then, 16.6 g (0.083 mol) of 4-Boc-piperidone was added to the reaction system all at once,-40 C for 20 minutes,Naturally warmed to room temperature and stirred for 3 hours.Until the reaction is completed,Add 300mL of water to quench the reaction,Extract three times with ether (200 mL x 3) and combine the organic phases,The resulting organic phase was dried over anhydrous sodium sulfate,Concentration gave an oil. The resulting oil was dissolved in 300 ml of toluene,7.78 g (0.083 mol) of lithium tetrafluoroborate was added,80 C for 2 hours,Cool to room temperature,Toluene was removed under reduced pressure,Add 300mL of water to quench the reaction,Extract three times with ether (200 mL x 3) and combine the organic phases,The organic phase was washed twice with saturated brine (200 mL x 2)The resulting organic phase was dried over anhydrous sodium sulfate,Concentration to give crude.The resulting crude product was isolated on a silica gel column,Get 15 grams of product,Yield 75%.
  • 15
  • [ 867-13-0 ]
  • [ 849203-60-7 ]
  • (E)-tert-butyl 1-(2-ethoxy-2-oxoethylidene)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
A mixture of ethyl 2-( diethoxyphosphoryl)acetate ( 1.4 g, 6.27 mmol, 1.5eq) and t-5 BuONa (602 mg, 6.27 mmol, 1.5eq) in THF (15 mL) was stirred at 0 C for 0.5 h. Tert-butylloxo-7 -azaspiro[3 .5]nonane-7 -carboxylate (1 g, 4.18 mmol, 1 eq) was added and the resultingmixture was stirred at room temperature overnight. The mixture was concentrated and the crudewas purified by column chromatography (silica gel: 300-400 mesh, PE/EtOAc = 3/1 to give pure(E)-tert-butyll-(2-ethoxy-2-oxoethylidene )-7 -azaspiro[3 .5]nonane-7 -carboxylate. LRMS m/z10 (M+Na) 332.1 found, 332.2 required.
  • 16
  • [ 79099-07-3 ]
  • [ 33462-81-6 ]
  • [ 849203-60-7 ]
YieldReaction ConditionsOperation in experiment
KHMDS (5.5 mL, 11 mmol, 2M in THF, 1.1eq) was added to a solution ofcyclopropyldiphenylsulfonium tetrafluoroborate (3.4 g, 11 mmol, 1.1eq) in THF (20 mL) at-78C. After stirring for 0.5 h, tert-butyl4-oxopiperidine-1-carboxylate (2 g, 10 mmol, 1eq) wasadded to the mixture. The reaction mixture was warmed to room temperature and stirred foranother 1 h. The mixture was quenched with sat. NH4Cl (30 mL) and extracted with EtOAc (2015 mL x 2), dried over anhydrous Na2S04, filtered and concentrated to afford a crude compound.The crude product and Si02 (6 g) in DCM (50 mL) was stirred at 40C for 3 h, concentrated andpurified by column chromatography (silica gel: 300-400 mesh, PE/EtOAc = 5/1) to afford pure tert-butyll-oxo-7-azaspiro[3.5]nonane-7-carboxylate. LRMS m/z (M+H) 240.2 found, 240.1required.
  • 17
  • [ 849203-60-7 ]
  • tert-butyl 1-(2-ethoxy-2-oxoethyl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 18
  • [ 849203-60-7 ]
  • tert-butyl 1-(2-hydroxyethyl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 19
  • [ 849203-60-7 ]
  • tert-butyl 1-(2-oxoethyl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 20
  • [ 849203-60-7 ]
  • (1S,2R)-7-difluoromethanesulfonyl-2-[(5R)-5H-imidazo[4,3-a]isoindol-5-yl]-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • (1R,2S)-7-difluoromethanesulfonyI-2-[(5S)-5H-imidazo[4,3-a]isoindol-5-yl]-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • 21
  • [ 849203-60-7 ]
  • 2-[[3-hydroxy-2-(5H-imidazo[1,5-b]isoindol-5-yl)-7-azaspiro[3.5]nonan-7-yl]sulfonyl]acetonitrile [ No CAS ]
  • 22
  • [ 849203-60-7 ]
  • (2S,3R)-2-[[3-hydroxy-2-((5S)-5H-imidazo[1,5-b]isoindol-5-yl)-7-azaspiro[3.5]nonan-7-yl]sulfonyl]acetonitrile [ No CAS ]
  • 23
  • [ 849203-60-7 ]
  • 1-((1R,2S)-1-hydroxy-2-((S)-5H-imidazo[5,1-a]isoindol-5-yl)-7-azaspiro[3.5]nonan-7-yl)-3-(pyridin-3-yl)propan-1-one [ No CAS ]
  • 24
  • [ 849203-60-7 ]
  • 2,2-difluoroethyl (1R,2S)-1-hydroxy-2-((S)-5H-imidazo[5,1-a]isoindol-5-yl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 25
  • [ 849203-60-7 ]
  • tert-butyl 2-(5H-imidazo[5,1-a]isoindol-5-yl)-1-oxo-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 26
  • [ 849203-60-7 ]
  • tert-butyl 1-hydroxy-2-[5H-imidazo[4,3-a]isoindol-5-yl]-7-azaspiro [3.5]nonane-7-carboxylate [ No CAS ]
  • 27
  • [ 849203-60-7 ]
  • tert-butyl (1S,2R)-1-hydroxy-2-((R)-5H-imidazo[5,1-a]isoindol-5-yl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 28
  • [ 849203-60-7 ]
  • tert-butyl (1R,2S)-1-hydroxy-2-((S)-5H-imidazo[5,1-a]isoindol-5-yl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
  • 29
  • [ 849203-60-7 ]
  • 2-(5H-imidizo[4,3-a]isoindol-5-yl)-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • 30
  • [ 849203-60-7 ]
  • (1S,2R)-2-[(5R)-5H-imidazo[4,3-a]isoindol-5-yl]-7-methanesulfonyl-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • (1R,2S)-2-[(5S)-5H-imidazo[4,3-a]isoindol-5-yl]-7-methanesulfonyl-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • 31
  • [ 849203-60-7 ]
  • (1S,2R)-7-fluoromethanesulfonyl-2-[(5R)-5H-imidazo[4,3-a]isoindol-5-yl]-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • (1R,2S)-7-fluoromethanesulfonyl-2-[(5S)-5H-imidazo[4,3-a]isoindol-5-yl]-7-azaspiro[3.5]nonan-1-ol [ No CAS ]
  • 32
  • [ 849203-60-7 ]
  • [ 1402838-08-7 ]
  • tert-butyl (2E)-1-oxo-2-([2-[1-(triphenylmethyl)-1H-imidazol-4-yl]phenyl]methylidene)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With calcium hydroxide; In ethanol; at 80℃; A slurry of tert-butyll-oxo-7-azaspiro [3.5jnonane-7-carboxylate (2.27 g, 9.49 mmol), 2-[1-(triphenylmethyi)-l H-imidazol-4-yl]benzaldehyde (4.04 g, 9.74 mnioi) and Ca(OH)2 (2.10 g, 28.33 mmol) in EtOH (100 mL) were mixed and stirred overnight at 80 C. The solids were filtered out. The resulting mixture was concentrated under vacuum. This resulted in 7.4 g (crude) of tert-butyl(2E)-1 -oxo-2-([2-[ I -(tripbenylmethyl)-IN-imidazol-4-yI] phenyljmethylidene)-7- azaspiro[3.5]nonane-7-crboxy1ate as a yellow solid. LCMS (ESI) rniz 636.2 [M+HJ
  • 33
  • [ 849203-60-7 ]
  • 1-hydroxy-7-azaspiro[1-3]nonan-7-tert-butyl carboxylate [ No CAS ]
  • 34
  • [ 849203-60-7 ]
  • N-boc-3-hydroxy-1,2-dioxa-9-azaspiro[5.5]undecane [ No CAS ]
 

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