Sodium hydride → HCID 18706986, compound

HRID 1422068Notes

Reaction equation

HRID 1422068 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3=[CH:24][C:25]([CH2:26][OH:27])=[C:21]4[N:22]3[C:17](=[CH:18][CH:19]=[CH:20]4)[C:16]=2[CH2:28][CH3:29])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CC(C)([O-])C.[K+].Cl.Cl[CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1>CN(C)C=O.O.C(O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:23]3=[CH:24][C:25]([CH2:26][O:27][CH2:40][CH2:41][N:42]4[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]4)=[C:21]4[N:22]3[C:17](=[CH:18][CH:19]=[CH:20]4)[C:16]=2[CH2:28][CH3:29])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 10883437HCID 10883437, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 18706986HCID 18706986, compoundYield 81.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(4-Benzyloxyphenyl)-1-ethyl-4-hydroxymethylpyrrolo[2,1,5-cd]indolizine (0.88 g, 1.26 mmol) was dissolved in 40 ml of dry dimethylformamide under a nitrogen atmosphere. Sodium hydride (80% in oil) (0.24 g, 8.0 mmol) and potassium tert-butoxide (0.1 g, 0.9 mmol) was added in portions and stirring was continued for ten minutes. 1-(2-chloroethyl)piperidine hydrochloride (0.74 g, 4 mmol) was added, and the solution was stirred for four hours. Ethanol (10 ml) was added dropwise, and the reaction mixture was diluted with 200 ml of water. The organic material was extracted into toluene (3×50 ml), and the combined organic layers were dried over magnesium sulfate. The solvent was evaporated and the crude product was purified by column chromatography over silica gel 60, using 10% of methanol in dichloromethane as the eluent to afford 0.505 g (81%) of 2-(4-benzyloxyphenyl)-1-ethyl-4-((2-piperidinoethoxy)methyl)pyrrolo[2,1,5-cd]indolizine as a yellow oil. MS(SP): m/z 492 (M+). 1H-NMR (CDCl3, 300 MHz) δ: 1.35-1.50 (m, 5H); 1.68 (m, 4H); 2.63 (m, 4H); 2.76 (t, 2H); 3.23 (q, 2H); 3.79 (t, 2H); 5.01 (s, 2H); 5.12 (s, 2H); 7.13 (d, 2H); 7.30-7.50 (m, 5H); 7.52 (s, 1H); 7.62 (t, 1H); 7.70 (d, 2H); 7.88 (d, 1H); 7.97 (d, 1H).

Workup

  1. waitwas continued for ten minutes
  2. stirringthe solution was stirred for four hours
  3. extractionThe organic material was extracted into toluene (3×50 ml)
  4. dry with materialthe combined organic layers were dried over magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe crude product was purified by column chromatography over silica gel 60

Sources & evidence

ORD record
ord-4e7236cf40f64baab3ec4e15d31bf1a4
Source dataset
uspto-grants-2000_06
Patent number
US06080754

Reaction notes

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