Water → 5-Benzyloxy-2-(4-benzyloxy-phenyl)-1-(4-(3-piperidin-1-yl-propoxy)-benzyl]-3-methyl-1H-indole

HRID 2410091Notes

Reaction equation

HRID 2410091 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28]Cl)=[CH:21][CH:20]=1)[C:13]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:32][CH:31]=1)=[C:12]2[CH3:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[K+].[NH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1.O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:47]3[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]3)=[CH:21][CH:20]=1)[C:13]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:32][CH:31]=1)=[C:12]2[CH3:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 4875Potassium IodideHCID 8082PiperidineHCID 121331385-Benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(3-chloro-propoxy)-benzyl]-3-methyl-1H-indole

Product 1

HCID 102116765-Benzyloxy-2-(4-benzyloxy-phenyl)-1-(4-(3-piperidin-1-yl-propoxy)-benzyl]-3-methyl-1H-indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-Benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(3-chloro-propoxy)-benzyl]-3-methyl-1H-indole No. 164 (3 g, 5.1 mmol), potassium iodide (2.5 g, 15.3 mmol) and piperidine (3.0 mL, 30.6 mmol) were heated in DMF (30 mL) at 100° C. for 18 hours. The reaction was worked up by pouring into water and extracting with ethyl acetate. The organic layer was washed with water, brine and dried over magnesium sulfate. The solution was concentrated to an oil and the product precipitated out by adding methanol. The product was obtained as a white solid: Mp=104-106° C.; 1H NMR (DMSO) 7.47 (d, 4H, J=7.5 Hz), 7.38 (q, 4H, J=7.9 Hz), 7.36-7.30 (m, 1H), 7.28 (d, 2H, J=8.3 Hz), 7.19 (d, 1H, J=8.8 Hz), 7.12-7.10 (m, 4H), 6.80 (dd, 1H, J=8.8, 2.0 Hz), 6.72 (s, 4H), 5.14 (s, 2H), 5.13 (s, 2H), 5.11 (s, 2H), 3.86 (t, 2H, J=6.4 Hz), 2.35-2.20 (m, 6H), 2.14 (s, 3H), 1.78-1.75 (m, 2H), 1.47-1.42 (m, 4H), 1.40-1.31 (m, 2H); MS eI m/z 650.

Workup

  1. extractionextracting with ethyl acetate
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationThe solution was concentrated to an oil
  5. customthe product precipitated out
  6. additionby adding methanol
  7. customThe product was obtained as a white solid

Sources & evidence

ORD record
ord-83272d9373d845769b54282d23a2f5d2
Source dataset
uspto-grants-2014_08
Patent number
US08815934B2

Reaction notes

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