Water → (4-Benzyl-1,4-oxazepan-2-ylmethyl)-phenyl amine

HRID 1246903Notes

Reaction equation

HRID 1246903 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na+].[I-].[CH2:10]([N:17]1[CH2:23][CH2:22][CH2:21][O:20][CH:19]([CH2:24]Cl)[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O>C(O)CCC.C(Cl)Cl>[CH2:10]([N:17]1[CH2:23][CH2:22][CH2:21][O:20][CH:19]([CH2:24][NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:18]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 962WaterHCID 5238Sodium IodideHCID 6115AnilineHCID 103993654-Benzyl-2-(chloromethyl)-1,4-oxazepane

Product 1

HCID 21904409(4-Benzyl-1,4-oxazepan-2-ylmethyl)-phenyl amine

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

Aniline (2.59 mL, 28.4 mmol) and NaI (4.06 g, 27.1 mmol) were added to a solution of 4-benzyl-2-chloromethyl-1,4-oxazepane (79) (6.49 g, 27.1 mmol) in n-butanol (68 mL, 0.4 M), and the reaction was heated to 110° C. until the reaction was judged complete by TLC (4 h). The reaction was cooled to room temperature, and water and CH2Cl2 were added. The organic layer was removed, and the aqueous layer was extracted with CH2Cl2 (2×). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to achieve (4-benzyl-1,4-oxazepan-2-ylmethyl)-phenyl amine 80, which was used without purification in the next reaction. 1H NMR (partial, CDCl3) 4.08–3.86 (3H, m), 3.80 (1H, d, J=13.3 Hz), 3.73 (1H, d, J=13.3 Hz), 3.22–3.05 (2H, m), 2.95–2.70 (3H, m), 2.64 (1H, dd, J=13.6, 7.6 Hz), 2.1–1.9 (2H, m) ppm. 13C NMR (CDCl3) 148.33, 139.38, 129.28, 129.11, 128.46, 127.23, 117.44, 113.13, 76.70, 67.49, 62.92, 59.35, 54.76,46.93, 30.75 ppm. LRMS: 296.68.

Workup

  1. customwas judged complete by TLC (4 h)
  2. temperatureThe reaction was cooled to room temperature
  3. customThe organic layer was removed
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customwas used without purification in the next reaction

Sources & evidence

ORD record
ord-f7b77b32d37a49eebfc04910d95134a9
Source dataset
uspto-grants-2006_10
Patent number
US07129228B2

Reaction notes

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