Acetic Acid → N-ethyl benzazepine

HRID 1630693Notes

Reaction equation

HRID 1630693 reaction equation
[NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH:12](=O)[CH3:13].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl>[CH2:12]([N:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[CH:2]1)[CH3:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 155596581H-1-Benzazepine

Product 1

HCID 18998293N-ethyl benzazepineYield 79.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the benzazepine (0.98 g, 3.9 mmol) from step E above in dichloromethane (50 mL) were added acetaldehyde (0.44 mL, 7.7 mmol), sodium triacetoxyborohydride (1.8 g, 8.3 mmol), acetic acid (0.2 mL), and 3 Å molecular sieves (1.0 g). The reaction solution was stirred at room temperature for 24 hours and then it was diluted with dichloromethane, washed with aqueous 1N sodium carbonate, dried over sodium sulfate and concentrated in vacuo. The crude product obtained was purified by flash column chromatography (dichloromethane to 95:4.5:0.5 dichloromethane/methanol/concentrated ammonium hydroxide) to give the desired N-ethyl benzazepine (0.53 g, 48%) as a yellow oil: 1H NMR (CDCl3, 500 MHz) δ 7.34 (t, J=7.5 Hz, 2H), 7.25 (t, J=7.5 Hz, 1H), 7.17 (d, J=7.5 Hz, 2H), 6.75 (d, J=2.5 Hz, 1H), 6.68-6.40 (br, 2H), 4.27 (d, J=8.5 Hz, 1H), 3.94 (d, J=13.5 Hz, 1H), 3.81 (d, J=14.5 Hz, 1H), 3.77 (s, 3H), 3.27-3.16 (br, 1H), 3.06-3.01 (m, 1H), 2.55-2.45 (m, 2H), 2.32-2.24 (m, 1H), 2.13-2.04 (br, 1H), 1.11 (t, J=7.0 Hz, 3H); ESI MS m/z 282 [M+H]+.

Workup

  1. washwashed with aqueous 1N sodium carbonate
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe crude product obtained
  5. customwas purified by flash column chromatography (dichloromethane to 95:4.5:0.5 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-fff82d056df74b87800dcec15ddbc0f4
Source dataset
uspto-grants-2014_07
Patent number
US08791101B2

Reaction notes

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