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Product Details of 2-Methylpropane-2-sulfinamide

CAS No. :146374-27-8
Formula : C4H11NOS
M.W : 121.20
SMILES Code : CC(C)(C)[S](=O)N
MDL No. :MFCD01863616

Safety of 2-Methylpropane-2-sulfinamide

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

Application In Synthesis of 2-Methylpropane-2-sulfinamide

* 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 [ 146374-27-8 ]

[ 146374-27-8 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 127842-54-0 ]
  • [ 146374-27-8 ]
  • [ 1112851-47-4 ]
YieldReaction ConditionsOperation in experiment
1-[3,4-Bis(difluoromethoxy)phenyl]methanamine hydrochloride (4-3)To a solution of <strong>[127842-54-0]3,4-bis(difluoromethoxy)benzaldehyde</strong> (4-2, 100 mg, 0.42 mmol, 1 equiv) in THF (840 uL) was added 2-methylpropane-2-sulfinamide (56 mg, 0.46 mmol, 1.1 equiv) and titanium ethoxide (440 uL, 2.10 mmol, 5.0 equiv), and the reaction mixture stirred at ambient temperature for 4.5 hours. The reaction mixture was then cooled to 0 C. and sodium borohydride (31.8 mg, 0.84 mmol, 2.0 equiv) was added portionwise and the reaction was stirred for an additional hour. Methanol (2 mL) was added slowly and the reaction mixture was partitioned between EtOAc (20 mL) and brine (20 mL) and filtered. The organic phase was dried over MgSO4 and concentrated to afford crude N-[3,4-bis(difluoromethoxy)benzyl]-2-methylpropane-2-sulfinamide, which was dissolved in methanol (2.2 mL). To the solution was added HCl (2 M in ether, 655 uL, 3 equiv), and the reaction mixture stirred for 30 minutes. It was then concentrated to afford the desired product (4-3) as a white solid. ESI+MS [M-NH2]+C9H7F4O2: 223.0 found, 223.0 required.
  • 2
  • [ 79099-07-3 ]
  • [ 146374-27-8 ]
  • [ 85482-13-9 ]
  • [ 919112-66-6 ]
  • 3
  • [ 1483-55-2 ]
  • [ 146374-27-8 ]
  • [ 1338209-67-8 ]
YieldReaction ConditionsOperation in experiment
94% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 15h;Inert atmosphere; General procedure for coupling reaction: An oven-dried resealable Schlenk tube were charged with Pd(OAc)2 (6.7 mg, 0.03 mmol), Xantphos (34.7 mg, 0.06 mmol), 2-methylpropane-2-sulfinamide (145 mg, 1.2 mmol) and Cs2CO3 (650 mg, 2.0 mmol). The Schlenk tube was evacuated and back-filled with argon. 4-bromo-2-methylbenzonitrile (196 mg, 1.0 mmol) and dioxane (3 ml) were added and the Schlenk tube was then sealed with a Teflon screw cap and placed in a preheated oil bath at 100oC for 15 h. After cooling of the reaction mixture to room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The product was purified by flash chromatography. Yield: 228 mg, 97 % [table-1, entry-5].
  • 4
  • [ 118994-86-8 ]
  • [ 146374-27-8 ]
  • [ 1394952-04-5 ]
YieldReaction ConditionsOperation in experiment
58.7% With titanium(IV) tetraethanolate; In tetrahydrofuran; at 65℃; for 12h; step 1 : Oxazole-5-carbaldehyde (1.0 g, 10.30 mmol), 2-methylpropane-2-sulfinamide (2.247 g, 18.54 mmol; CASRN 146374-27-8), and tetraethoxytitanium (8.460 g, 37.09 mmol) were placed in THF (15 mL) and heated to 65 C for 12 h. The reaction was cooled and poured onto water. The solids were filtered off and the filtrate was extracted with EtOAc. The layers were separated and the organic layer was concentrated. The resulting residue was purified by Si02 chromatography (20-25% EtOAc/hexane) to afford (E)-2-methyl-N-(oxazol-5- ylmethylene)propane-2-sulfinamide (20, 1.211 g, 6.047 mmol, 58.70 % yield).
58.7% With titanium(IV) tetraethanolate; In tetrahydrofuran; at 65℃; for 12h;Inert atmosphere; [001851 step 1 : Oxazole-5-carbaldehyde (1.0 g, 10.30 mmol), 2-methylpropane-2-sulfinamide (2.247 g, 18.54 mmol; CASRN 146374-27-8), and tetraethoxytitanium (8.460 g, 37.09 mmol) were stirred in THF (15 mL) and heated to 65 C for 12 h under nitrogen. The reaction was cooled and poured onto water. The solids were filtered off and the filtrate was extracted with EtOAc. The layers were separated and the organic layer was dried (MgS04), filtered and concentrated. The resulting residue was purified by Si02 chromatography eluting with an EtOAc hexane gradient (20 to 25% EtOAc) to afford 1.21 1 g (58.7%) of (E)-2-methyl-N-(oxazol-5-ylmethylene)propane-2- sulfinamide (20).
  • 5
  • titanium(IV) tetraethanolate [ No CAS ]
  • [ 146374-27-8 ]
  • [ 161957-59-1 ]
  • (R,E)-N-(1-(3-chloro-2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In tetrahydrofuran; ethyl acetate; Step 1: (R,E)-N-(1-(3-chloro-2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (18a) To a solution of <strong>[161957-59-1]1-(3-chloro-2-fluorophenyl)ethanone</strong> (5.60 g, 31.5 mmol) and (R)-2-methylpropane-2-sulfinamide (5.72 g, 47.2 mmol) in THF (50.0 mL) was added tetraethoxytitanium (16.50 mL, 79 mmol) and the overall bright yellow solution was heated at 70 C. for overnight. The reaction was slightly cooled with ice-water bath, then was added EtOAc (50 mL), NaHCO3 (10 mL), and brine (10 mL). The slurry was filtered through a short path of Celite and the wet cake was washed with EtOAc. The resulted bright yellow solution was phase separated, and the organic layer was concentrated to afford the title compound (8.3 g, 30.1 mmol, 96% yield) as a light yellow oil. This material was used in the next step without purification. MS m/z=276.0 [M+H]+. Calculated for C12H15ClFNOS: 275.77.
  • 6
  • [ 704-38-1 ]
  • [ 146374-27-8 ]
  • bis(2-thienyl)methanone [ No CAS ]
  • 7
  • [ 22929-52-8 ]
  • [ 146374-27-8 ]
  • N-(dihydrofuran-3(2H)-ylidene)-2-methylpropane-2-sulfinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With titanium(IV) tetraethanolate; In tetrahydrofuran; at 20 - 60℃; for 8h;Inert atmosphere; Intermediate 334A: N-(Dihydrofuran-3(2H)-ylidene)-2-methylpropane-2-sulfinamide To a stirred solution of <strong>[22929-52-8]dihydrofuran-3(2H)-one</strong> (0.901 mL, 11.62 mmol) in THF (20 mL) at RT under nitrogen was added Ti(OEt)4 (4.87 mL, 23.23 mmol), 2-methylpropane-2-sulfinamide (1.549 g, 12.78 mmol) and the reaction mixture was stirred at 60 C. for 8 h. The reaction mixture was quenched with a saturated aq. solution of NaHCO3 with vigorous stirring. The precipitate was filtered and washed with EtOAc and the aq. layer was extracted with EtOAc. The combined organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography (40 g REDISEP column, eluting with 25% ethyl acetate in hexanes). Fractions containing the product were combined and evaporated to afford Compound 334A as a pale yellow liquid (700 mg, 32%). The crude compound was taken to next step without purification.
With titanium(IV) isopropylate; In tetrahydrofuran; at 60℃; A solution of <strong>[22929-52-8]dihydrofuran-3(2H)-one</strong> (300 mg, 3.48 mmol), 2-methylpropane-2- sulfinamide (422 mg, 3.48 mmol), and titanium(IV) isopropoxide (1.07 ml, 3.66 mmol) in THF (5 ml) was heated to 60 C overnight. The reaction mixture was cooled to room temperature, diluted with EtOAc, and poured into brine. The suspension was filtered and the layers were separated. The organic layer was dried over MgS04, filtered, and concentrated. The residue was used without purification. LCMS calculated for CgHi6N02S (M+H)+: m/z = 190.1, found: 190.1.
  • 8
  • [ 146374-27-8 ]
  • [ 121246-96-6 ]
  • (E)-N-((3-chloropyrazin-2-yl)methylene)-2-methylpropane-2-sulfinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(II) sulfate; In dichloromethane; at 20℃; for 17h; To a solution of <strong>[121246-96-6]3-chloropyrazine-2-carbaldehyde</strong> (900 mg, 6.31 mmol) and 2- methylpropane-2-sulfinamide (842 mg, 6.95 mmol) in methylene chloride (10 mL), was added cupric sulfate (1.109 g, 6.95 mmol). The mixture was stirred at room temperature for 17 h overnight. The mixture was diluted with ethylacetate and washed with water, brine, dried over MgSC>4, filtered and concentrated. The crude was purified by column chromatography (24 g silica gel, 50% ethyl acetacetate in hexanes) to afford product (E)-N-((3-chloropyrazin-2- yl)methylene)-2-methylpropane-2-sulfinamide.
  • 9
  • [ 41042-12-0 ]
  • [ 146374-27-8 ]
  • (E)-N-(1-propyl-2-oxoindolin-3-ylidene)-2-methylpropane-2-sulfinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With titanium(IV) isopropylate; In dichloromethane;Reflux; Inert atmosphere; General procedure: To a solution of N-substituted isatin (1.17 mmol, 1.0 eq) in anhydrous CH2Cl2 (2.9 mL, 0.4 M), Ti(OiPr)4 (2.34 mmol, 2.0 eq) and 2-methyl-2-propanesulfinamide (1.4 mmol, 1.2 eq) were added. The solution was refluxed until complete disappearance of the starting materials (monitored by TLC). The reaction was quenched by adding saturated aq. NaHCO3 (15 mL) and diluted with CH2Cl2 (15 mL). The biphasic solution was filtered through a pad of Celite and the organic phase washed with water (2 x 15 mL), dried over Na2SO4 and the solvent was evaporated under reduced pressure. The crude was purified by flash chromatography (FC), using hexane/EtOAc/CH2Cl2 (gradient from 9:1:10 to 5/5/10) as eluent.
  • 10
  • [ 689291-89-2 ]
  • [ 146374-27-8 ]
  • C11H13BrINOS [ No CAS ]
  • 11
  • [ 1260878-78-1 ]
  • [ 146374-27-8 ]
  • N-((4-chloro-3-fluoropyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; caesium carbonate; Synthesis of N-((4-chloro-3-fluoropyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide. To a solution of <strong>[1260878-78-1]4-chloro-3-fluoropicolinaldehyde</strong> (26.0 g, mixtutre, 163.0 mmol) in DCM (100 mL) was added cesium carbonate (96.0 g, 293.3 mmol) and 2-methylpropane-2-sulfinamide (19.8 g, 163.0 mmol) at RT. The reaction mixture was stirred for 3 h at RT. After the reaction was complete, the reaction mixture was filtrated and washed with DCM three times. To the combined mixture was added MeOH (40 mL), and then the resulting mixture was cooled to 0 C. by ice-water bath. Sodium borohydride (15.5 g, 409.0 mmol) was added slowly in portions. The reaction mixture was warmed up to RT and stirred at this temperature for 2 h. The reaction was quenched with H2O carefully. The resulting mixture was extracted with DCM (100 mL*3), the combined organic solvent was dried by sodium sulfate, filtered, and concentrated to get crude N-((4-chloro-3-fluoropyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide (43.3 g, crude) as yellow solid. ESI-MS [M+H]+: 265.1.
  • 12
  • [ 34595-26-1 ]
  • [ 146374-27-8 ]
  • C16H24N2OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
83.5% With pyridinium p-toluenesulfonate; In tetrahydrofuran; for 8h;Reflux; Compound 187.1 g (0.46 mol, 1.0 eq), pyridine 4-methylbenzenesulfonate 3.5 g (13.8 mmol, 0.03 eq), (R)-(+)-tert-butylsulfinyl 111.5 g (0.92 mol, 2.0 Eq) and 435g of tetrahydrofuran were placed in a reaction flask, heated to reflux for 8 hours, HPLC controlled raw material reaction < 3%, cooled, 2g of triethylamine was added, stirred for 30 minutes, the solvent was concentrated under reduced pressure to obtain crude product. The crude product was recrystallized from n-heptane to give white solid 112.2g, HPLC purity 98.1%, yield 83.5%.
 

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