Acetic Acid → Ethyl 4-(4-ethyl-1,4-diazepan-1-yl)benzoate

HRID 1911468Notes

Reaction equation

HRID 1911468 reaction equation
[N:1]1([C:8]2[CH:18]=[CH:17][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:19](=O)[CH3:20].C(O)(=O)C.C([BH3-])#N.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.CO>[CH2:19]([N:4]1[CH2:5][CH2:6][CH2:7][N:1]([C:8]2[CH:18]=[CH:17][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][CH:9]=2)[CH2:2][CH2:3]1)[CH3:20]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 177Acetaldehyde2×HCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 18425301Ethyl 4-(1,4-diazepan-1-yl)benzoate

Product 1

HCID 66589981Ethyl 4-(4-ethyl-1,4-diazepan-1-yl)benzoateYield 76.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of ethyl 4-(1,4-diazepan-1-yl)benzoate (0.621 g, 2.5 mmol), acetaldehyde (0.701 mL, 12.50 mmol) and acetic acid (0.286 mL, 5.00 mmol) in tetrahydrofuran (30 mL), methanol (3 mL) was treated with sodium cyanoborohydride (0.393 g, 6.25 mmol) at 20° C. The resulting solution was stirred at 60° C. for 18 h. The reaction mixture was cooled and extra amount of acetaldehyde (2.146 mL, 38 mmol) and sodium triacetoxyborohydride (1.060 g, 5.00 mmol) were added. The reaction was stirred at room temperature for 18 h. The reaction mixture was filtered and evaporated to dryness. The residue was dissolved in 2N HCl (5 ml) and methanol (20 ml). The solution of crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford ethyl 4-(4-ethyl-1,4-diazepan-1-yl)benzoate (0.526 g, 76%)

Workup

  1. temperatureThe reaction mixture was cooled
  2. stirringThe reaction was stirred at room temperature for 18 h
  3. filtrationThe reaction mixture was filtered
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in 2N HCl (5 ml)
  6. customThe solution of crude product was purified by ion exchange chromatography
  7. washThe desired product was eluted from the column
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-40bdd9bb683f4326b1deac30d80d9bb8
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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