Cesium carbonate → 6-Cyclopropylmethoxy-5-(2-methyl-pyrrolidin-1-yl)-pyridine-2-carboxylic acid

HRID 632010

反応式

HRID 632010 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([C:13]([OH:15])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.[CH3:16][CH:17]1[CH2:21][CH2:20][CH2:19][NH:18]1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:10]1([CH2:9][O:8][C:7]2[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=[CH:3][C:2]=2[N:18]2[CH2:19][CH2:20][CH2:21][CH:17]2[CH3:16])[CH2:12][CH2:11]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 130032-MethylpyrrolidineHCID 634876Binap, (A+-)-HCID 710875435-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid

生成物 1

HCID 710879326-Cyclopropylmethoxy-5-(2-methyl-pyrrolidin-1-yl)-pyridine-2-carboxylic acid収率 36.9%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

実験手順

Under an atmosphere of nitrogen, a solution of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (Example 9 d, 0.4 g, 1.5 mmol), 2-methylpyrrolidine (CAN 765-38-8, 188 mg, 2.2 mmol), R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (CAN 76189-55-4, 183 mg, 0.3 mmol), tris-(dibenzylidene-acetone)dipalladium (CAN 51364-51-3, 135 mg, 0.15 mmol) and cesium carbonate (1.9 g, 6 mmol) in toluene (50 mL) was heated to 90° C. overnight. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in water (10 mL) and extracted with ethyl acetate (30 mL), the pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid and the resulting mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate and evaporated. The residue was purified by column chromatography (silica gel, 10 g, 50% ethyl acetate in petroleum ether) to yield the title compound (0.15 g, 36.9%) as yellow solid; MS (EI): m/e=277.2 [M+H]+.

後処理

  1. customwas heated to 90° C. overnight
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in water (10 mL)
  4. extractionextracted with ethyl acetate (30 mL)
  5. additionthe pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid
  6. extractionthe resulting mixture was extracted with ethyl acetate (3×30 mL)
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. customevaporated
  10. customThe residue was purified by column chromatography (silica gel, 10 g, 50% ethyl acetate in petroleum ether)

出典と根拠

ORDレコード
ord-ffe41ccebcac497db6f9346aec012aac
出典データセット
uspto-grants-2016_04
特許番号
US09321727B2

関連ノート

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