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

HRID 630304Notes

Reaction equation

HRID 630304 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) δ7.98 (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-bd432251ebf54fcab22e912cc922c5bf
Source dataset
uspto-grants-2016_04
Patent number
US09315509B2

Reaction notes

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