3,4-dihydro-2H-pyran → Indole

HRID 1602105Notes

Reaction equation

HRID 1602105 reaction equation
O1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.[N:7]1([CH2:12][C:13]2C=CC(NN)=C[CH:14]=2)C=NC=N1>O1CCOCC1.O>[NH:7]1[C:12]2[C:4](=[CH:5][CH:6]=[CH:14][CH:13]=2)[CH:3]=[CH:2]1

Participants

4

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 74720491-(4-Hydrazinylbenzyl)-1H-1,2,4-triazole

Product 1

HCID 798IndoleYield 37.2%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

3,4-Dihydro-2H-pyran (3.9 ml, 42.7 mmol) was added to a stirred solution of 4-(1,2,4-triazol-1-ylmethyl)phenylhydrazine (EP 497,512; 4.0 g, 21.1 mmol) in dioxane/water/5N HCl (38 ml/14 ml/4.7 ml) and stirred at room temperature for 1.75 h. The solution was then refluxed for 1.5 h and the solvent removed under vacuum. The residue was taken up into CH2Cl2 and saturated aqueous K2CO3 solution. The aqueous was separated and further extracted with CH2Cl2 (×4). The combined organic extracts were dried (MgSO4) and evaporated and the residue chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (80:8:1) to give the title-indole (0.919 g, 17%), δ(250 MHz, CDCl3) 1.91-2.03 (2H, m, CH2), 2.84 (2H, t, J=7.9 Hz, CH2), 3.73 (2H, t, J=7.9 Hz, CH2), 5.43 (2H, s, CH2), 7.04 (1H, d, J=2.3 Hz, Ar--H), 7.11 (1H, dd, J=2.3 and 8.3 Hz, Ar--H), 7.35 (1H, d, J=8.3 Hz, Ar--H), 7.58 (1H, s, Ar--H). 7.97 (1H, s, Ar--H). 8.02 (1H, s, Ar--H), 8.18 (1H, s, NH).

Workup

  1. temperatureThe solution was then refluxed for 1.5 h
  2. customthe solvent removed under vacuum
  3. customThe aqueous was separated
  4. extractionfurther extracted with CH2Cl2 (×4)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customevaporated
  7. customthe residue chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (80:8:1)

Sources & evidence

ORD record
ord-54304cb52ad642f88b61b2c60f4dfdbd
Source dataset
uspto-grants-1999_11
Patent number
US05981529

Reaction notes

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