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

HRID 16470

Reaction equation

HRID 16470 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-e2ad19f2a9f6489ab15b36cf06dd7004
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Linked notes

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