Potassium Iodide → 1-{3-[7-(1-Hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-4-phenyl-piperidin-4-ol

HRID 917129Notes

Reaction equation

HRID 917129 reaction equation
[C:1]1([C:7]2([OH:13])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C(C)=CC=CC=1C.[I-].[K+].Br[CH2:25][CH2:26][CH:27]=[C:28]1[C:34]2[CH:35]=[CH:36][CH:37]=[N:38][C:33]=2[CH2:32][O:31][C:30]2[CH:39]=[CH:40][C:41]([C:43]([OH:46])([CH3:45])[CH3:44])=[CH:42][C:29]1=2>C(O)(C)C>[OH:46][C:43]([C:41]1[CH:40]=[CH:39][C:30]2[O:31][CH2:32][C:33]3[N:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:28](=[CH:27][CH2:26][CH2:25][N:10]3[CH2:11][CH2:12][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)([OH:13])[CH2:8][CH2:9]3)[C:29]=2[CH:42]=1)([CH3:45])[CH3:44]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 79372,6-LutidineHCID 963874-Phenylpiperidin-4-olHCID 666859992-[5-(3-Bromo-propylidene)-5,1 1-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-propan-2-ol

Product 1

HCID 667583481-{3-[7-(1-Hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-4-phenyl-piperidin-4-olYield 50%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the 4-phenyl-piperidin-4-ol (0.212 g, 1.2 mmol) in isopropanol was added 2,6-lutidine (0.240 mL, 2.1 mmol) and catalytic potassium iodide. This mixture was heated to 80° C., and treated with 2-[5-(3-Bromo-propylidene)-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-propan-2-ol (0.224 g, 0.6 mmol), added in portions over 1 h. The solution was then stirred at 80° C. for an additional 14 h. The reaction was concentrated in vacuo, then purified by Isco flash chromatography (15% methanol/85% methylene chloride) to yield the title compound (0.140 g, 50%). 1H-NMR (CDCl3): δ 1.12 (t, 3H), 1.57(s, 6H), 2.67–2.80 (m, 4H), 1.95–2.11 (m, 2H), 2.34–2.41 (m, 2H), 2.43–2.54 (m, 2H), 2.88 (d, 2H), 3.22 (q, 2H), 3.43 (m, 1H), 5.28 (bs, 2H), 6.12 (t, 1H), 6.60 (d, 2H), 6.80 (d, 1H), 7.13 (d, 2H), 7.21–7.30 (m, 2H), 7.45 (s, 1H), 7.56 (d, 1H), 8.48 (dd, 1H). ESI-MS m/z: 534 (M+1), retention time 2.47.

Workup

  1. additionadded in portions over 1 h
  2. concentrationThe reaction was concentrated in vacuo
  3. custompurified by Isco flash chromatography (15% methanol/85% methylene chloride)

Sources & evidence

ORD record
ord-5ad3682e03d04538826c3c867c3b24c1
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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