Pyrrolidine → HCID 11694411, compound

HRID 252500Notes

Reaction equation

HRID 252500 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14](=[O:16])[CH3:15])=[CH:4]1)[CH3:2].[CH2:17]([N:19]1C2C(=CC=C(OC)C=2)C=C1)C.COC(OC)N(C)C.N1CCCC1.Cl.ON>O>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]2[O:16][N:19]=[CH:17][CH:15]=2)=[CH:4]1)[CH3:2]

Participants

7

Reactant 5

HCID 31268PyrrolidineHCID 78373Dimethylformamide dimethyl acetalHCID 443297Hydroxyamine hydrochlorideHCID 59425473HCID 59425473, compoundHCID 59425954HCID 59425954, compound

Product 1

HCID 11694411HCID 11694411, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

1-(1-Ethyl-6-methoxy-1H-indol-3-yl)ethanone (100 mg, 0.46 mmol), prepared from 1-ethyl-6-methoxy-1H-indole by the procedure described in example 1L, is heated with 1.5 mL of dimethylformamide dimethylacetal and 100 μL of pyrrolidine at 110° C. overnight. The dimethylformamide dimethylacetal is then concentrated in vacuo. The residue is redissolved in 1.25 mL of EtOH and 250 μL of H2O, and is treated with hydroxyamine hydrochloride (66 mg, 0.95 mmol) and heated at 80° C. for 2 h. Partitioning between H2O and EtOAc and drying and concentration of the organic phase followed by purification by silica gel chromatography (EtOAc/CH2Cl2, 5/95) gives 1-ethyl-3-isoxazol-5-yl-6-methoxy-1H-indole as a white solid (72 mg, 66%).

Workup

  1. concentrationThe dimethylformamide dimethylacetal is then concentrated in vacuo
  2. dissolutionThe residue is redissolved in 1.25 mL of EtOH
  3. customPartitioning between H2O and EtOAc
  4. customdrying
  5. customconcentration of the organic phase followed by purification by silica gel chromatography (EtOAc/CH2Cl2, 5/95)

Sources & evidence

ORD record
ord-24646bbce85243e5bb1bbaaa08b3b69f
Source dataset
uspto-grants-2011_01
Patent number
US07868037B2

Reaction notes

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