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 925234Notes

Reaction equation

HRID 925234 reaction equation
[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]

Participants

6

Reactant 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

Product 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 esterYield 56.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-44c5248677c54ed4a6125ed92269091b
Source dataset
uspto-grants-2016_03
Patent number
US09284277B2

Reaction notes

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