Oxalyl chloride → 5-Iodo-1-oxo-2,3,7,8,10,11-hexahydro-1H-4-oxa-9-aza-cyclohepta[a]naphthalene-9-carboxylic acid ethyl ester

HRID 925234ノート

反応式

HRID 925234 の反応式
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([O:18][CH2:19][CH2:20][C:21]([OH:23])=O)[C:15]([I:17])=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[C:13]3[C:21](=[O:23])[CH2:20][CH2:19][O:18][C:14]=3[C:15]([I:17])=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]

参加物

6

反応物 3

HCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 867253407-(2-Carboxy-ethoxy)-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

生成物 1

HCID 867253415-Iodo-1-oxo-2,3,7,8,10,11-hexahydro-1H-4-oxa-9-aza-cyclohepta[a]naphthalene-9-carboxylic acid ethyl ester収率 56.9%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

Into a 100 ml flask, the product from step (e) (312 mg, 0.72 mmol) dissolved in DCM (20 ml) was added. The solution was cooled to 0° C., and oxalyl chloride (94 μL, 1.07 mmol) was added, followed by 2 drops of DMF. After 30 minutes, volatiles were evaporated in vacuo and the residue was dissolved in fresh DCM (20 ml) and cooled to 0° C. Aluminum chloride (386 mg, 2.88 mmol) was then added and the reaction mixture stirred for 1 hour. The reaction was quenched with saturated aqueous NH4Cl, and the organic layer was extracted with DCM (3×). The combined DCM extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the crude product. Purification by silica-gel chromatography (gradient elution: 0 to 40% EtOAc in hexanes) gave the sub-title compound as a light yellow solid (170 mg). 1H NMR (300 MHz, CDCl3) δ 7.69 (s, 1H); 4.56 (t, J=6.3 Hz, 2H); 4.12 (q, J=7.2 Hz, 2H); 3.68-3.51 (m, 6H); 2.85 (t, J=6.6 Hz, 4H); 1.23 (t, J=7.2 Hz, 3H); MS: ESI (positive): 416 (M+H).

後処理

  1. additionwas added
  2. customvolatiles were evaporated in vacuo
  3. dissolutionthe residue was dissolved in fresh DCM (20 ml)
  4. temperaturecooled to 0° C
  5. customThe reaction was quenched with saturated aqueous NH4Cl
  6. extractionthe organic layer was extracted with DCM (3×)
  7. washThe combined DCM extracts were washed with brine
  8. dry with materialdried over Na2SO4, and solvent
  9. customevaporated in vacuo
  10. customto give the crude product
  11. customPurification
  12. washby silica-gel chromatography (gradient elution: 0 to 40% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-44c5248677c54ed4a6125ed92269091b
出典データセット
uspto-grants-2016_03
特許番号
US09284277B2

反応ノート

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