Ethyl Acetate → N-[6-[2-chloro-4-(phenylmethoxy)phenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

HRID 497664ノート

反応式

HRID 497664 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[Cl:16].C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:31]2[CH:39]=[C:38]3[C:34]([C:35]([NH:48][C:49](=[O:53])[CH2:50][CH2:51][CH3:52])=[N:36][N:37]3[CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])=[CH:33][CH:32]=2)O1.C(OCC)(=O)C>O.O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:16][C:3]1[CH:4]=[C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:7][C:2]=1[C:31]1[CH:39]=[C:38]2[C:34]([C:35]([NH:48][C:49](=[O:53])[CH2:50][CH2:51][CH3:52])=[N:36][N:37]2[CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:45])[CH3:46])=[CH:33][CH:32]=1

参加物

8

反応物 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 22319493N-[6-(4,4,5,5-tetramethyl [1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamideHCID 223195014-(Benzyloxy)-1-bromo-2-chlorobenzene

生成物 1

HCID 22319610N-[6-[2-chloro-4-(phenylmethoxy)phenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide収率 56%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

実験手順

1.95 g of 1-bromo-2-chloro-4-(phenylmethoxy)benzene, described previously, 1.11 g of sodium carbonate in 36 cm3 of water and 347 mg of tetrakis(triphenylphosphine)palladium are added to 2 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously in Example 56, in 180 cm3 of dioxane. The medium is then refluxed for 2 hours and the mixture is allowed to return to room temperature, 200 cm3 of ethyl acetate and 100 cm3 of water are added and the resulting mixture is filtered through a sinter funnel packed with Celite. The combined organic phases are washed with 100 cm3 of distilled water and then with 100 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (85/15 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 1.34 g of N-[6-[2-chloro-4-(phenylmethoxy)phenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of a yellow oil.

後処理

  1. temperatureThe medium is then refluxed for 2 hours
  2. customto return to room temperature
  3. filtrationthe resulting mixture is filtered through a sinter funnel
  4. washThe combined organic phases are washed with 100 cm3 of distilled water
  5. dry with materialwith 100 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa; 45° C.)
  8. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (85/15 by volume)
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)

出典と根拠

ORDレコード
ord-f3013ee970db4c00becda000df7dfc9a
出典データセット
uspto-grants-2005_09
特許番号
US06949579B2

反応ノート

読み込み中…