Propanoic acid, 3-iodo- → 7-(2-Carboxy-ethoxy)-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

HRID 925233Notes

Reaction equation

HRID 925233 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([OH:18])[C:15]([I:17])=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].[H-].[Na+].I[CH2:22][CH2:23][C:24]([OH:26])=[O:25]>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([O:18][CH2:22][CH2:23][C:24]([OH:26])=[O:25])[C:15]([I:17])=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8856Propanoic acid, 3-iodo-HCID 24758Sodium hydrideHCID 867253397-Hydroxy-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

Product 1

HCID 867253407-(2-Carboxy-ethoxy)-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl esterYield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Into a 100 ml flask, the product of step (d) (1.28 g, 3.54 mmol) dissolved in DMF (15 ml) was added. The solution was cooled to 0° C. and NaH (354 mg, 8.86 mmol) was added, followed by 3-iodopropionic acid (1.06 g 5.31 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 1.5 hours, after which time it was heated to 70° C. for an additional 1 hour. The reaction mixture was cooled to room temperature and quenched by the addition of water (100 ml) and 2M NaOH (15 ml). The aqueous mixture was washed with EtOAc (2×), acidified with 2M HCl to pH 2, and extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give crude product. Purification by silica-gel chromatography (gradient elution: 0 to 60% EtOAc in hexanes) gave the sub-title compound as an off-white solid (580 mg) and recovered starting material (515 mg). MS: ESI (positive): 434 (M+H).

Workup

  1. additionwas added
  2. temperatureto warm to room temperature
  3. temperatureafter which time it was heated to 70° C. for an additional 1 hour
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customquenched by the addition of water (100 ml) and 2M NaOH (15 ml)
  6. washThe aqueous mixture was washed with EtOAc (2×)
  7. extractionextracted with EtOAc (3×)
  8. washThe combined EtOAc extracts were washed with brine
  9. dry with materialdried over Na2SO4, and solvent
  10. customevaporated in vacuo
  11. customto give crude product
  12. customPurification
  13. washby silica-gel chromatography (gradient elution: 0 to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-93ecfdcd765141c4b8b1351a0c877156
Source dataset
uspto-grants-2016_03
Patent number
US09284277B2

Reaction notes

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