Morpholine → tert-butyl cyclopropyl{[1-(3-methoxypropyl)-4-morpholin-4-yl-1H-indol-3-yl]methy}carbamate

HRID 872034Notes

Reaction equation

HRID 872034 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+].Br[C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[C:12]([CH2:24][N:25]([CH:33]1[CH2:35][CH2:34]1)[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:13][N:14]2[CH2:19][CH2:20][CH2:21][O:22][CH3:23]>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.C1(C)C=CC=CC=1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:33]1([N:25]([CH2:24][C:12]2[C:11]3[C:15](=[CH:16][CH:17]=[CH:18][C:10]=3[N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[N:14]([CH2:19][CH2:20][CH2:21][O:22][CH3:23])[CH:13]=2)[C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:31])[CH3:29])[CH2:35][CH2:34]1

Participants

8

Reactant 3

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 86645632tert-butyl {[4-bromo-1-(3-methoxypropyl)-1H-indol-3-yl]methyl}cyclopropylcarbamate

Product 1

HCID 59494507tert-butyl cyclopropyl{[1-(3-methoxypropyl)-4-morpholin-4-yl-1H-indol-3-yl]methy}carbamate

Reagents, catalysts & solvents 4

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Morpholine (73.5 μL), cetyltrimethylammoniumbromide (14.6 mg), bis(tri-tert-butylphosphine)palladium(0) (41 mg) and 50% aqueous solution of sodium hydroxide (96 μL) were added to a solution of tert-butyl {[4-bromo-1-(3-methoxypropyl)-1H-indol-3-yl]methy}cyclopropylcarbamate (205 mg) in toluene (3 ml) and the mixture was stirred under argon atmosphere at 90° C. for 23 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The obtained solution was washed with water and saturated brine successively, dried over magnesium sulfate and concentrated in vacuo. The resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=20/1 to 3/2) to give tert-butyl cyclopropyl{[1-(3-methoxypropyl)-4-morpholin-4-yl-1H-indol-3-yl]methy}carbamate (280 mg) as a yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe obtained solution was washed with water and saturated brine successively
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=20/1 to 3/2)

Sources & evidence

ORD record
ord-e9121c2e8655457db9f71a4596fe2744
Source dataset
uspto-grants-2015_03
Patent number
US08975252B2

Reaction notes

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