Triethylamine → methyl 4-[[hexahydro-4-[2-[4-(phenylmethyl)phenoxy]ethyl]-1H-1,4-diazepin-1-yl]methyl]benzoate

HRID 1046325Notes

Reaction equation

HRID 1046325 reaction equation
[N:1]1([CH2:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5]CCN1.I[CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:25][CH:24]=1.[CH2:36]([N:38](CC)CC)[CH3:37].C(=O)(O)[O-].[Na+]>C1COCC1>[C:30]1([CH2:29][C:26]2[CH:27]=[CH:28][C:23]([O:22][CH2:21][CH2:20][N:38]3[CH2:5][CH2:6][CH2:7][N:1]([CH2:8][C:9]4[CH:10]=[CH:11][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:17][CH:18]=4)[CH2:37][CH2:36]3)=[CH:24][CH:25]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 684890121-(2-Iodoethoxy)4-(benzyl)benzeneHCID 68490555HCID 68490555, compound

Product 1

HCID 68490327methyl 4-[[hexahydro-4-[2-[4-(phenylmethyl)phenoxy]ethyl]-1H-1,4-diazepin-1-yl]methyl]benzoateYield 27.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 4-[(hexahydro-1H-diazepin-1-yl)methyl]benzoate (109 mg, 0.44 mmol) and 1-(2-iodoethoxy)-4-(benzyl)benzene (120 mg, 0.44 mmol) in THF (4 mL) was treated with triethylamine (112 μl, 0.80 mmol) and heated at reflux for 5 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 55 mg of methyl 4-[[hexahydro-4-[2-[4-(phenylmethyl)phenoxy]ethyl]-1H-1,4-diazepin-1-yl]methyl]benzoate; 1H NMR (300 MHz, CDCl3) δ 7.98 (d, 2H), 7.42 (d, 2H), 7.28 (dd, 2H), 7.17 (d, 2H), 7.18 (dd, 1H), 7.09 (d, 2H), 6.82 (d, 2H), 4.05 (t, 2H), 3.92 (s, 2H), 3.91 (s, 3H), 3.69 (s, 2H), 2.97 (t, 2H), 2.88 (m, 2H), 2.84 (m, 2H), 2.69 (m, 4H), 1.81 (m, 2H) ppm.

Workup

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

Sources & evidence

ORD record
ord-6225e4e7e8f04cce977ecd5475708896
Source dataset
uspto-grants-2013_10
Patent number
US08569303B2

Reaction notes

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