Cesium carbonate → Tert-butyl 4-(4-methoxycarbonylphenyl)-1,4-diazepane-1-carboxylate

HRID 1911330Notes

Reaction equation

HRID 1911330 reaction equation
I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[N:12]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(C1CCCCC1=O)(=O)C>CN(C=O)C.[Cu](I)I>[CH3:9][O:8][C:6]([C:5]1[CH:10]=[CH:11][C:2]([N:15]2[CH2:16][CH2:17][CH2:18][N:12]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][CH2:14]2)=[CH:3][CH:4]=1)=[O:7]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 134002-AcetylcyclohexanoneHCID 69273Methyl 4-iodobenzoateHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylate

Product 1

HCID 57362684Tert-butyl 4-(4-methoxycarbonylphenyl)-1,4-diazepane-1-carboxylateYield 13.2%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Methyl 4-iodobenzoate (1.00 g, 3.82 mmol, 1.0 eq) was dissolved in DMF and tert-butyl 1,4-diazepane-1-carboxylate (765 mg, 3.82 mmol, 1.0 eq), caesium carbonate (2.49 g, 7.63 mmol, 2.0 eq), 2-acetylcyclohexanone (101 μl, 0.76 mmol, 0.20 eq [20 mol %]) and copper iodide (37 mg, 0.19 mmol, 0.05 eq [5 mol %]) were added. The reaction mixture was stirred at 90° C. under nitrogen for 7 h. The reaction mixture was evaporated, dissolved in DCM (50 ml), washed with water (20 ml), saturated ammonium chloride solution (20 ml), dried over MgSO4, filtered and evaporated. The crude product was purified by silica column chromatography, eluting with 0-1% MeOH in DCM. The product containing fractions were combined, evaporated and dried in vacuo to give tert-butyl 4-(4-methoxycarbonylphenyl)-1,4-diazepane-1-carboxylate (168 mg, 13%) as a yellow oil.

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutiondissolved in DCM (50 ml)
  3. washwashed with water (20 ml), saturated ammonium chloride solution (20 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by silica column chromatography
  8. washeluting with 0-1% MeOH in DCM
  9. additionThe product containing fractions
  10. customevaporated
  11. customdried in vacuo

Sources & evidence

ORD record
ord-096a79951b1349ad893bd00a3ea4eb3d
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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