Cesium carbonate → 5-(Bis(2,2,2-trifluoroethyl)amino)-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid methyl ester

HRID 632219

반응식

HRID 632219 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](Br)=[C:7]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)[N:6]=1)=[O:4].[F:17][C:18]([F:27])([F:26])[CH2:19][NH:20][CH2:21][C:22]([F:25])([F:24])[F:23].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N:20]([CH2:19][C:18]([F:17])([F:26])[F:27])[CH2:21][C:22]([F:25])([F:24])[F:23])=[C:7]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)[N:6]=1)=[O:4]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 78999Bis(2,2,2-trifluoroethyl)amineHCID 634876Binap, (A+-)-HCID 71087286Methyl 5-bromo-6-(cyclopropylmethoxy)picolinate

생성물 1

HCID 866747735-(Bis(2,2,2-trifluoroethyl)amino)-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid methyl ester수율 29.7%

시약·촉매·용매 2

HCID 9832798Tris(dibenzylideneacetone) dipalladium촉매HCID 1140Toluene용매

실험 절차

Under a nitrogen atmosphere, a solution of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid methyl ester (Example 114 a, 1 g, 3.5 mmol), bis(2,2,2-trifluoroethyl)amine (1.90 g, 10 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (CAN 98327-87-8, 0.435 g, 1 mmol), tris(dibenzylideneacetone) dipalladium (CAN 51364-51-3, 0.32 g, 0.35 mmol) and cesium carbonate (CAN 534-17-8, 3.4 g, 10 mmol) in toluene (50 mL) was reacted overnight at 110° C. The reaction mixture was concentrated under reduced pressure, dissolved in water, extracted with ethyl acetate (50 mL), the aqueous layer was adjusted to pH 2 with conc. HCl, then extracted with ethyl acetate (3×50 mL), washed with brine (2×50 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 10 g, 20% ethyl acetate in petroleum ether) to yield the title compound (0.5 g, 29.7%) as a yellow oil; MS: m/e=387.1 [M+H]+.

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutiondissolved in water
  3. extractionextracted with ethyl acetate (50 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washwashed with brine (2×50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (silica gel, 10 g, 20% ethyl acetate in petroleum ether)

출처 및 근거

ORD 기록
ord-75ea6733d01e40608073b143920db332
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321727B2

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