Triethylamine → methyl 4-[(hexahydro-1H-1,4-diazepin-1-yl)methyl]benzoate

HRID 1046279Notes

Reaction equation

HRID 1046279 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[N:1]1([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 68163Hexahydro-1,4-diazepineHCID 256687Methyl 4-(bromomethyl)benzoateHCID 516892Sodium Bicarbonate

Product 1

HCID 28881272methyl 4-[(hexahydro-1H-1,4-diazepin-1-yl)methyl]benzoateYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Alternatively, a mixture of hexahydro-1H-1,4-diazepine (17.47 g, 174.4 mmol) and methyl 4-(bromomethyl)benzoate (5.0 g, 21.8 mmol) was heated with triethylamine (24 mL, 174.4 mmol) in tetrahydrofuran (872 mL) to reflux for three hours. After cooling, the mixture was treated with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Flash chromatography gave 3.04 g of methyl 4-[(hexahydro-1H-1,4-diazepin-1-yl)methyl]benzoate, 1H NMR (300 MHz, CDCl3) δ 7.98 (d, 2H), 7.42 (d, 2H), 3.90 (s, 3H), 3.70 (s, 2H), 2.97 (m, 2H), 2.91 (m, 2H), 2.67 (m, 2H), 2.66 (m, 2H), 1.77 (m, 2H).

Workup

  1. temperatureto reflux for three hours
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6c67fb5fa2c04075a6baac0a154fd64b
Source dataset
uspto-grants-2013_10
Patent number
US08569303B2

Reaction notes

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