Morpholine → 1-methyl-6-morpholin-4-yl-1H-indole

HRID 651758Notes

Reaction equation

HRID 651758 reaction equation
C1OCCOCCOCCOCCOCCOC1.I[C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[CH:25][N:26]2[CH3:29])=[CH:22][CH:21]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:29][N:26]1[C:27]2[C:23](=[CH:22][CH:21]=[C:20]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:28]=2)[CH:24]=[CH:25]1

Participants

7

Reactant 5

HCID 8083MorpholineHCID 2855718-Crown-6HCID 634876Binap, (A+-)-HCID 217090906-iodo-1-methyl-1H-indoleHCID 23676156Sodium t-butoxide

Product 1

HCID 217090601-methyl-6-morpholin-4-yl-1H-indoleYield 94%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

An oven dried flask was flushed with argon and charged with 18-crown-6 (15 g, 56.7 mmol), 6-iodo-1-methyl-1H-indole (10.4 g, 40.46 mmol), morpholine (4.3 mL, 48.6 mmol), sodium t-butoxide (5.42 g, 54.7 mmol), tris(dibenzylidene acetone)dipalladium (0) (186 mg, 0.20 mmol) and 2,2′-bis(diphenylphosphino)-1,1-binaphthyl) (380 mg, 0.61 mmol). The flask was flushed with argon for 10 min and dry THF (80 mL) was added. The mixture was stilled at room temperature for 5 h, then diluted with ether and washed with brine. The organic layer was dried (MgSO4), evaporated and the crude product was purified by chromatography on silica gel using 5-30% ether/hexanes to give 1-methyl-6-morpholin-4-yl-1H-indole (8.17 g, 94%). [Ref: Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 1997, 62, 6066.]

Workup

  1. customAn oven dried flask
  2. customwas flushed with argon
  3. customThe flask was flushed with argon for 10 min
  4. additiondry THF (80 mL) was added
  5. additiondiluted with ether
  6. washwashed with brine
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customevaporated
  9. customthe crude product was purified by chromatography on silica gel using 5-30% ether/hexanes

Sources & evidence

ORD record
ord-c40bea081dbe43a281cda6647b5c528f
Source dataset
uspto-grants-2001_08
Patent number
US06281356B1

Reaction notes

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