Triethylamine → 3-Tert-butoxycarbonylamino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 1675558ノート

反応式

HRID 1675558 の反応式
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][C:9]=1[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].C(N(CC)CC)C.[C:26]([C:30]#[CH:31])([CH3:29])([CH3:28])[CH3:27].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.C(Cl)Cl.[Cu]I.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]>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:31]#[C:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

参加物

9

反応物 4

HCID 8471TriethylamineHCID 135123,3-Dimethyl-1-butyneHCID 634876Binap, (A+-)-HCID 57356848Methyl 5-bromo-3-((tert-butoxycarbonyl)amino)thiophene-2-carboxylate

生成物 1

HCID 249893453-Tert-butoxycarbonylamino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
60 °C

実験手順

To a solution of 3-(tert-butoxycarbonyl)amino-5-bromo-thiophene-2-carboxylic acid methyl ester (4.566 g, 13.58 mmol) in dry DMF (40 mL) are added copper (I) iodide (52 mg, 0.27 mmol), Pd2 dba3 (622 mg, 0.68 mmol) and triethylamine (9.46 mL, 67.9 mmol), and the mixture is deoxygenated by bubbling nitrogen through solution for 10 min. Then tert-butylacetylene (6.62 mL, 54.32 mmol) and BINAP (676 mg, 1.09 mmol) are added to the mixture, and it is heated at 60° C. overnight under nitrogen. The mixture is diluted with CH2Cl2 and filtered through celite washing with CH2Cl2. Filtrate is washed with brine, organic fraction is separated, dried over Na2SO4, concentrated, and the residue is purified by column chromatography on silica gel eluting with gradient of EtOAc in hexane to give of 5-(3,3-dimethyl-but-1-ynyl)-3-(tert-butoxycarbonyl)amino-thiophene-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ, ppm: 1.27 (s, 9H), 1.51 (s, 9H), 3.84 (s, 3H), 7.87 (s, 1H), 9.24 (br.s, 1H)

後処理

  1. customthe mixture is deoxygenated
  2. customby bubbling nitrogen through solution for 10 min
  3. filtrationfiltered
  4. washthrough celite washing with CH2Cl2
  5. washFiltrate is washed with brine, organic fraction
  6. customis separated
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customthe residue is purified by column chromatography on silica gel eluting with gradient of EtOAc in hexane

出典と根拠

ORDレコード
ord-9c7211bb84054280b15e9d1c70ff00c2
出典データセット
uspto-grants-2011_08
特許番号
US08003685B2

反応ノート

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