Iodine → N-(1-(4-chlorobenzyl)-3-pent-4-enoylcyclobutyl)formamide

HRID 1778598Notes

Reaction equation

HRID 1778598 reaction equation
[Mg].II.Br[CH2:5][CH2:6][CH:7]=[CH2:8].[Cl:9][C:10]1[CH:29]=[CH:28][C:13]([CH2:14][C:15]2([NH:25][CH:26]=[O:27])[CH2:18][CH:17]([C:19](N(OC)C)=[O:20])[CH2:16]2)=[CH:12][CH:11]=1>C1COCC1>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][C:15]2([NH:25][CH:26]=[O:27])[CH2:16][CH:17]([C:19](=[O:20])[CH2:8][CH2:7][CH:6]=[CH2:5])[CH2:18]2)=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 807IodineHCID 21241Homoallyl bromideHCID 5462224Magnesium2×HCID 895144553-(4-chlorobenzyl)-3-formamido-N-methoxy-N-methylcyclobutanecarboxamide

Product 1

HCID 89514331N-(1-(4-chlorobenzyl)-3-pent-4-enoylcyclobutyl)formamideYield 97.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Magnesium powder (0.548 g, 22.6 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 until the color had dissipated (approximately 30 minutes). While refluxing, a second solution of 4-bromo-1-buten (2.3 mL, 22.6 mmol) in dry THF (5 mL) was added. After 12 min, the mixture was cooled 0° C. and added to a solution of 3-(4-chlorobenzyl)-3-formamido-N-methoxy-N-methylcyclobutanecarboxamide (0.5 g, 1.61 mmol) in dry THF (30 mL). After 2 h, the reaction was allowed to warm to room temperature and stir overnight. The reaction was quenched with saturated aqueous NH4Cl and 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 (0.48 g) that was used to the next step without further purification. ESI MS found for C17H20ClNO2 m/z [306.3 (M+1), 328.3 (M+Na+), 304.5 (M−1)].

Workup

  1. temperaturethe solution was heated to
  2. temperaturea gentle reflux until the color
  3. custom(approximately 30 minutes)
  4. temperatureWhile refluxing
  5. waitAfter 2 h
  6. temperatureto warm to room temperature
  7. customThe reaction was quenched with saturated aqueous NH4Cl
  8. extractionextracted with diethyl ether (×2)
  9. washThe combined organic layers were washed successively with 1M HCl, water and saturated aqueous sodium chloride
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-80f6fce1b8ff450ebe4c2100ca17afb6
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

Loading…