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

HRID 28748

반응식

HRID 28748 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 23948Rhodium촉매HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-26f3412499504428b7ac0815f2d448ad
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07419994B2

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