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Triethylamine → 4-(4-Fluorophenyl)-1-[3-(5,11-dihydro-7-hydroxy-[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine-4-ol

HRID 457067
Notes
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Reaction equation

HRID 457067 reaction equation
Br[CH2:2][CH2:3][CH:4]=[C:5]1[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[O:9][C:8]2[CH:16]=[CH:17][CH:18]=[C:19]([OH:20])[C:7]=2[CH2:6]1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2([OH:34])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C(N(CC)CC)C>CN(C=O)C>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2([OH:34])[CH2:29][CH2:30][N:31]([CH2:2][CH2:3][CH:4]=[C:5]3[C:15]4[C:10](=[N:11][CH:12]=[CH:13][CH:14]=4)[O:9][C:8]4[CH:16]=[CH:17][CH:18]=[C:19]([OH:20])[C:7]=4[CH2:6]3)[CH2:32][CH2:33]2)=[CH:24][CH:23]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 774974-(4-Fluorophenyl)piperidin-4-olHCID 667582405-(3-Bromopropylidene)-5,11-dihydro-7-hydroxy-[1]benzoxepino[2,3-b]pyridine

Product 1

HCID 667581834-(4-Fluorophenyl)-1-[3-(5,11-dihydro-7-hydroxy-[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine-4-olYield 39%

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Procedure

To a solution of 5-(3-bromopropylidene)-5,11-dihydro-7-hydroxy-[1]benzoxepino[2,3-b]pyridine (2.59 g) in DMF (10 ml) was added 4-(4-Fluorophenyl)-4-hydroxypiperidine (1.02 g) and triethylamine (835 μM). The solution was stirred at room temperature for 23 hours. The reaction was quenched with water, extracted with ethyl acetate, and evaporated in vacuo. The residue was purified by silica gel chromatography (87:10:3 ethyl acetate: methanol:triethylamine) to yield 0.9 g (39%) of the title compound. 1H-NMR (DMSO) d: 1.64–1.69 (2H, m), 1.74–1.85 (2H, m), 2.27–2.52 (8H, m), 4.81 (1H, s), 5.16 (2H, brs), 6.08 (1H, t), 6.62–6.71 (3H, m), 7.12 (2H, t), 7.40–7.51 (3H, m), 7.72 (1H, dd), 8.48 (1H, dd), 9.09 (1H, s). ESI-MS m/z: 447 (M+1).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. customevaporated in vacuo
  4. customThe residue was purified by silica gel chromatography (87:10:3 ethyl acetate: methanol:triethylamine)

Sources & evidence

ORD record
ord-d8744e0f8de34466a8d0fe35d79322e3
Source dataset
uspto-grants-2007_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07186729B2

Reaction notes

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