Ethyl Acetate → (4-Chloro-indan-1-yl)-acetic acid ethyl ester

HRID 28748

反応式

HRID 28748 の反応式
[H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][C:8]2=O.[CH3:14][CH2:15][O:16][C:17]([CH3:19])=[O:18]>C1COCC1.[Rh]>[CH2:15]([O:16][C:17](=[O:18])[CH2:19][CH:8]1[C:9]2[C:5](=[C:4]([Cl:3])[CH:12]=[CH:11][CH:10]=2)[CH2:6][CH2:7]1)[CH3:14]

参加物

6

反応物 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 113326814-chloro-2,3-dihydro-1H-inden-1-one

生成物 1

HCID 23549532(4-Chloro-indan-1-yl)-acetic acid ethyl ester

試薬・触媒・溶媒 2

HCID 23948Rhodium触媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Use of 2-chlorocinnamic acid (Intermediate TWENTYTHREE-1) (commercially available from Aldrich) in the applicable process steps described in Method TWENTY produced 4-chloro-indan-1-one (Intermediate TWENTYFOUR-1). Triethylphosphonoacetate (3.5 mL, 17.2 mmol) was added to a mixture of NaH (0.69 g, 12.2 mmol) in THF (25 mL). After 30 m, a solution of 4-chloro-indan-1-one (Intermediate TWENTYFOUR-1) (1.46 g, 8.8 mmol) in THF (20 mL) was added to the mixture. The reaction mixture was allowed to stir for 16 h at rt. The solution was quenched with water and diluted with EtOAc. The layers were separated and the organic phase was dried over MgSO4, filtered and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel with 3% EtOAc:hexane. The fractions that contained the unsaturated esters were collected and evaporated to give the product, 1.67 g. The mixture of esters (1.67 g, 7.06 mmol) in EtOAc was hydrogenated in the presence of 5% Rh on Alumina (0.14 g) at 40-50 psi H2 at rt for 2 d. The mixture was filtered through a plug of Celite® and concentrated in vacuo to produce (4-chloro-indan-1-yl)-acetic acid ethyl ester (Intermediate TWENTYFOUR-2). Use of (4-chloro-indan-1-yl)-acetic acid ethyl ester (Intermediate TWENTYFOUR-2) in the applicable process steps described in Method SEVENTEEN and Method A produced 4-(4-chloro-indan-1-ylmethyl)-1,3-dihydro-imidazole-2-thione (Compound 166).

後処理

  1. customThe solution was quenched with water
  2. additiondiluted with EtOAc
  3. customThe layers were separated
  4. dry with materialthe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customwere collected
  8. customevaporated
  9. customto give the product, 1.67 g
  10. filtrationThe mixture was filtered through a plug of Celite®
  11. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-26f3412499504428b7ac0815f2d448ad
出典データセット
uspto-grants-2008_09
特許番号
US07419994B2

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