Morpholine → 2-(1-ethyl-6-fluoro-4-hydroxy-1H-indol-3-yl)-1-morpholinoethanone

HRID 1404099Notes

Reaction equation

HRID 1404099 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[C:7]([OH:13])[CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([CH2:14][C:15]([OH:17])=O)=[CH:4]1)[CH3:2].[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.O>[CH2:1]([N:3]1[C:11]2[C:6](=[C:7]([OH:13])[CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([CH2:14][C:15]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:17])=[CH:4]1)[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 583039722-(1-ethyl-6-fluoro-4-hydroxy-1H-indol-3-yl)acetic acid

Product 1

HCID 583040262-(1-ethyl-6-fluoro-4-hydroxy-1H-indol-3-yl)-1-morpholinoethanoneYield 91.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of compounds 11-3 (119 mg, 0.5 mmol) in DMF (2 mL) was added morpholine (66 uL, 0.75 mmol), triethylamine (0.24 mL, 1.75 mmol) and BOP (265 mg, 0.6 mmol). The reaction mixture was stirred at room temperature overnight. The solution was diluted with water and extracted with EtOAc. Combined organic layers were washed with 1N HCl, water, brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (silica gel, ethyl acetate:hexanes: 25:75 to 100%) gave pure 11-4 (140 mg, 91%) as a white foam.

Workup

  1. extractionextracted with EtOAc
  2. washCombined organic layers were washed with 1N HCl, water, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography (silica gel, ethyl acetate:hexanes: 25:75 to 100%)

Sources & evidence

ORD record
ord-54c252789ac54488855cdf85c131c9fd
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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