1-Chloro-4-iodobenzene → HCID 68191113, compound

HRID 1615537Notes

Reaction equation

HRID 1615537 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[C:9]([NH:16][CH2:17][C:18]#[CH:19])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C(N(CC)C(C)C)(C)C>ClCCl.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:19]#[C:18][CH2:17][NH:16][C:9](=[O:10])[O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 125101-Chloro-4-iodobenzeneHCID 81531DiisopropylethylamineHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamate

Product 1

HCID 68191113HCID 68191113, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-chloro-4-iodobenzene (6.40 g, 26.8 mmol) and N-boc propargylamine (5.00 g, 32.2 mmol) in dichloromethane (117 mL) was added copper (I) iodide (0.204 g, 1.07 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.754 g, 1.07 mmol). The solution was degassed with argon for 10 minutes, then N,N-diisopropylethylamine (14.3 mL, 81.9 mmol) was added and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated, then the residue was diluted with EA and water. The layers were separated and the aqueous layer was extracted twice more with EA. The combined organic layers were dried over anhydrous sodium sulfate, filtered, then concentrated. The residue was purified using column chromatography on silica gel (80 g Analogix column, gradient hexanes to 20% EA in hexanes over 20 minutes) to give the product (5.97 g, 84%). LCMS: (AA) ES+ 210, 212 (Boc group fragmentation). 1H NMR (400 MHz, d6-DMSO) δ: 7.47-7.39 (m, 4H), 7.35 (s, 1H), 3.97 (d, J=5.6 Hz, 2H), 1.39 (s, 9H).

Workup

  1. customThe solution was degassed with argon for 10 minutes
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with EA and water
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice more with EA
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified
  10. customon silica gel (80 g Analogix column, gradient hexanes to 20% EA in hexanes over 20 minutes)

Sources & evidence

ORD record
ord-26af8c3f85c2435a9d49bfef16896a01
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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