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

HRID 630344Notes

Reaction equation

HRID 630344 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-9afbcfaabf3b436ab7b1220e414bfe97
Source dataset
uspto-grants-2016_04
Patent number
US09315509B2

Reaction notes

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