Triethylamine → hexahydro-1-[[4-(phenylmethoxy)phenyl]methyl]-1H-1,4-diazepine

HRID 16511

Reaction equation

HRID 16511 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:12][CH:11]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[C:18]1([CH2:17][O:16][C:13]2[CH:12]=[CH:11][C:10]([CH2:9][N:1]3[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]3)=[CH:15][CH:14]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 68163Hexahydro-1,4-diazepineHCID 700424-Benzyloxybenzyl chlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 11197238hexahydro-1-[[4-(phenylmethoxy)phenyl]methyl]-1H-1,4-diazepineYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of hexahydro-1H-1,4-diazepine (3.44 g, 34.4 mmol) and 1-(chloromethyl)-4-(benzyloxy)benzene (2.0 g, 8.6 mmol) was treated with triethylamine (4.8 ml, 34.4 mmol) in 100 mL tetrahydrofuran and heated at reflux for 4 h. After cooling, the mixture was treated with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Flash chromatography gave 2.0 g of hexahydro-1-[[4-(phenylmethoxy)phenyl]methyl]-1H-1,4-diazepine; 1H NMR (300 MHz, CDCl3) δ 7.44 (d, 2H), 7.39 (dd, 2H), 7.32 (dd, 1H), 7.26 (d, 2H), 6.93 (d, 2H), 5.05 (s, 2H), 3.60 (s, 2H), 2.96 (m, 2H), 2.89 (m, 2H), 2.68 (m, 2H), 2.65 (m, 2H), 1.75 (m, 2H) ppm.

Workup

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

Sources & evidence

ORD record
ord-7b63ce0800b14aa2be9ea3cff8245e13
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Linked notes

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