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

HRID 630349Notes

Reaction equation

HRID 630349 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-50cffe2eb9074dd399dd3a7e00ed7343
Source dataset
uspto-grants-2016_04
Patent number
US09315509B2

Reaction notes

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