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Chemical Structure| 1380331-28-1 Chemical Structure| 1380331-28-1

Structure of 1380331-28-1

Chemical Structure| 1380331-28-1

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Product Details of [ 1380331-28-1 ]

CAS No. :1380331-28-1
Formula : C12H15FN2O4
M.W : 270.26
SMILES Code : O=C(OC)C1=C(F)C=NC(NC(OC(C)(C)C)=O)=C1
MDL No. :MFCD23162870
Boiling Point : No data available

Safety of [ 1380331-28-1 ]

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 [ 1380331-28-1 ]

* 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 [ 1380331-28-1 ]

[ 1380331-28-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 885588-14-7 ]
  • [ 4248-19-5 ]
  • [ 1380331-28-1 ]
YieldReaction ConditionsOperation in experiment
56% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; at 100℃; for 6.0h;Inert atmosphere; A mixture of <strong>[885588-14-7]methyl 2-bromo-5-fluoropyridine-4-carboxylate</strong> (6.64 g, 28.4 mmol), tert- Butyl carbamate (4.0 g, 34.1 mmol), cesium carbonate (13.0 g, 39.8 mmol), X-phos (657 mg, 1.1 mmol) and Pd(dba)2 (520 mg, 0.9 mmol) in 1,4-dioxane (100 mL) was purged with nitrogen and then stirred at 100 C under nitrogen for 6 h. The mixture was cooled to RT, diluted with water (100 mL), and extracted with EA (150 mL x 2). The combined organic phase was washed with brine, dried over MgSO4, and concentrated. The residue was chromatographed, eluting with 0- 30% EA in hexane to give methyl 2-((tert-butoxycarbonyl)amino)-5-fluoropyridine-4- carboxylate as a white solid (4.5 g, 56%). MS (ESI+) m/z 271.1 (M+H)+, retention time: 1.81 min. (Method A). 1H NMR (400 MHz, CDCl3) δ 1.52 (s, 9H), 3.96 (s, 3H), 8.24 (s, 1H), 8.40 (d, 1H), 9.00 (s, 1H).
56% With caesium carbonate; bis(dibenzylideneacetone)-palladium(0); XPhos; In 1,4-dioxane; at 100℃; for 6.0h;Inert atmosphere; A mixture of <strong>[885588-14-7]methyl 2-bromo-5-fluoropyridine-4-carboxylate</strong> (6.64 g, 28.4 mmol), tert-Butyl carbamate (4.0 g, 34.1 mmol), cesium carbonate (13.0 g, 39.8 mmol), X-phos (657 mg, 1.1 mmol) and Pd(dba)2 (520 mg, 0.9 mmol) in 1,4-dioxane (100 mL) was purged with nitrogen and then stirred at 100 C under nitrogen for 6 h. The mixture was cooled to RT, diluted with water (100 mL), and extracted with EA (150 mL x 2). The combined organic phase was washed with brine, dried over MgS04, and concentrated. The residue was chromatographed, eluting with 0-30% EA in hexane to give methyl 2-((tert-butoxycarbonyl) amino)-5-fluoropyridine-4-carboxylate as a white solid (4.5 g, 56%). MS (ESI+) m/z 271.1 (M+H)+, retention time: 1.81 min. (Method A). 'H NMR (400 MHz, CDCl3) d 1.52 (s, 9H), 3.96 (s, 3H), 8.24 (s, 1H), 8.40 (d, 1H), 9.00 (s, 1H).
55.7% With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 5.5h;Inert atmosphere; b) methyl 2-(tert-butoxycarbonylamino)-5-fluoroisonicotinate To an nitrogen purged suspension of <strong>[885588-14-7]methyl 2-bromo-5-fluoroisonicotinate</strong> (2.8 g, 12 mmol) in dioxane (55 ml) is added successively tert-butyl carbamate (1.68 g, 14.4 mmol), tris(dibenzylidene-acetone)dipalladium(0) (219 mg, 239 umol), 4,5-bis(diphenylphos-phino)-9,9-dimethylxanthene (277 mg, 479 mmol) and cesium carbonate (5.46 g, 16.8 mmol). The mixture is then stirred for 5.5 hrs at 100 C. under nitrogen atmosphere. After 5 min at 100 C. the redbrown suspension has turned green. The mixture is diluted with ethyl acetate, washed twice with water, once with brine, dried with magnesium sulfate and the solvent is removed in vacuo. The product is isolated by chromatography of the residue (3.85 g) on a 70 g Silicycle silica cartridge using a heptane/ethyl acetate 10-40% gradient affording methyl 2-(tert-butoxycarbonylamino)-5-fluoroisonicotinate (1.8 g, 55.7%) as a light yellow solid. MS: m/z=271.2 (M+H+).
55.7% With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 5.5h;Inert atmosphere; To an nitrogen purged suspension of <strong>[885588-14-7]methyl 2-bromo-5-fluoroisonicotinate</strong> (2.8 g, 12 mmol) in dioxane (55 ml) is added successively tert-butyl carbamate (1.68 g, 14.4 mmol),tris(dibenzylidene-acetone)dipalladium(0) (219 mg, 239 umol), 4,5-bis(diphenylphos-phino)-9,9- dimethylxanthene (277 mg, 479 ummol) and cesium carbonate (5.46 g, 16.8 mmol). The mixture is then stirred for 5.5 hrs at 100C under nitrogen atmosphere. After 5 min at 100C the redbrown suspension has turned green. The mixture is diluted with ethyl acetate, washed twice with water, once with brine, dried with magnesium sulfate and the solvent is removed in vacuo. The product is isolated by chromatography of the residue (3.85 g) on a 70 g Silicycle silica cartridge using a heptane / ethyl acetate 10 - 40% gradient affording methyl 2-(tert- butoxycarbonylamino)-5-fluoroisonicotinate (1.8 g, 55.7%) as a light yellow solid. MS: m/z= 271.2 (M+H+).
8.43 g With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 24.0h;Inert atmosphere; Sonication; To a solution of methyl 2-bromo-5-fluoro-pyridine-4-carboxylate (10.3 g, 44.0 mmol) in 1,4- dioxane (150 mL) were added tert-butyl carbamate (6.18 g, 52.8 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.86 g, 0.88 mmol), 4,5 -bis(diphenylphosphino)-9,9- dimethylxanthene (1.02 g, 1.76 mmol) and cesium carbonate (20.08 g, 61.6 mmol). The reaction mixture was purged with argon, sonicated, caped and left to stir at 90C for 24h. The reaction mixture was cooled, filtrated through pad of celite and washed with ethyl acetate. Mother liquor was washed with water (2x 100 mL) and brine (100 mL) and evaporated under reduced pressure affording the cmde product, which was triturated from ethyl acetate affording methyl 2-(tert-butoxycarbonylamino)-5 - fluoro-pyridine-4-carboxylate (8.43g). LCMS: MW (calcd): 270.1; MS (ES, m/z): 215.41 (M+H-56).

 

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