Trifluoroacetic acid → 7-Hydroxy-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

HRID 925232Notes

Reaction equation

HRID 925232 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(O)(C(F)(F)F)=O.C1C(=O)N([I:32])C(=O)C1>C(#N)C.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([OH:17])[C:15]([I:32])=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 120273N-IodosuccinimideHCID 584953637-Hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

Product 1

HCID 867253397-Hydroxy-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl esterYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Into a 100 ml flask, the product of step (c) (503 mg, 2.14 mmol) dissolved in acetonitrile (20 ml) and TFA (2 ml) was added. To this stirred solution, NIS (458 mg, 2.03 mmol) was added. After stirring for 30 minutes at room temperature, the reaction was diluted with water (200 ml) and extracted with EtOAc (3×). The combined EtOAc 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 yellow solid (616 mg). 1H NMR (300 MHz, CDCl3) δ 7.39 (s, 1H); 6.77 (s, 1H); 5.42 (bs, 1H); 4.18 (q, J=7.2 Hz, 2H); 3.61-3.52 (m, 4H); 2.81-2.72 (m, 4H); 1.26 (t, J=6.9 Hz, 3H); MS: ESI (positive): 362 (M+H).

Workup

  1. extractionextracted with EtOAc (3×)
  2. washThe combined EtOAc extracts were washed with brine
  3. dry with materialdried over Na2SO4, and solvent
  4. customevaporated in vacuo
  5. customto give the crude product
  6. customPurification
  7. washby silica-gel chromatography (gradient elution: 0 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d044c66b751244ab9a4a336612142775
Source dataset
uspto-grants-2016_03
Patent number
US09284277B2

Reaction notes

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