Iodine → N-(1-(4-chlorophenyl)-3-pent-4-enoylcyclobutyl)benzamide

HRID 1778592Notes

Reaction equation

HRID 1778592 reaction equation
[Mg].II.Br[CH2:5][CH2:6][CH:7]=[CH2:8].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([NH:26][C:27](=[O:34])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:19][CH:18]([C:20](=[O:25])N(OC)C)[CH2:17]2)=[CH:12][CH:11]=1>C1COCC1>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2([NH:26][C:27](=[O:34])[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:17][CH:18]([C:20](=[O:25])[CH2:8][CH2:7][CH:6]=[CH2:5])[CH2:19]2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 807IodineHCID 21241Homoallyl bromideHCID 5462224Magnesium2×HCID 89514268N-(1-(4-chlorophenyl)-3-(methoxy(methyl)carbamoyl)cyclobutyl)benzamide

Product 1

HCID 89514447N-(1-(4-chlorophenyl)-3-pent-4-enoylcyclobutyl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Magnesium powder (1.05 g, 42.0 mmol) was placed into a round-bottomed flask with a small piece of iodine. Dry THF was added to cover the magnesium and the solution was heated to a gentle reflux for 30 minutes. While refluxing, a second solution of 4-bromo-1-buten (4.72 mL, 42.0 mmol) in dry THF (5 mL) was added. After 12 min, the mixture was cooled to room temperature and added to a solution of N-(1-(4-chlorophenyl)-3-(methoxy(methyl)carbamoyl)cyclobutyl)benzamide (1.12 g, 3.0 mmol) in dry THF (30 mL). After 2 h, the reaction was quenched with saturated aqueous NH4Cl. 1M HCl was added to pH-3 and the solution was extracted with diethyl ether (×2). The combined organic layers were washed successively with 1M HCl, water and saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated to give the crude product that was used to the next step without further purification. 1H NMR (CDCl3, 600 MHz) δ 7.76 (d, J=7.2 Hz, 2H), 7.47-7.50 (m, 1H), 7.46 (d, J=8.7 Hz, 2H), 7.40-7.43 (m, 2H), 7.33 (d, J=8.7 Hz, 2H), 6.77 (s, 1H), 5.72-5.80 (m, 1H), 4.92-5.01 (m, 2H), 3.16-3.22 (m, 1H), 2.90-2.94 (m, 2H), 2.82-2.86 (m, 2H), 2.54 (t, J=7.3 Hz, 2H), 2.30-2.35 (m, 2H). ESI MS found for C22H22ClNO2 m/z [368.4/370.4 (M+1)].

Workup

  1. temperaturethe solution was heated to
  2. temperaturea gentle reflux for 30 minutes
  3. temperatureWhile refluxing
  4. waitAfter 2 h
  5. customthe reaction was quenched with saturated aqueous NH4Cl
  6. addition1M HCl was added to pH-3
  7. extractionthe solution was extracted with diethyl ether (×2)
  8. washThe combined organic layers were washed successively with 1M HCl, water and saturated aqueous sodium chloride
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-09a30fe19a464eb78898db83d23a4da4
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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