Ethyl Acetate → HCID 86604030, compound

HRID 1351975Notes

Reaction equation

HRID 1351975 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH2:11][C@H:12]([N:14]([CH2:22][C@@H:23]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)[O:24][Si:25]([CH2:30][CH3:31])([CH2:28][CH3:29])[CH2:26][CH3:27])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[C@@H:55]([CH3:64])[C:56]([N:58]2[CH2:63][CH2:62][O:61][CH2:60][CH2:59]2)=[O:57])(=O)=O)=CC=1.C(OCC)(=O)C>CN(C)C=O>[CH3:13][C@@H:12]([N:14]([CH2:22][C@@H:23]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)[O:24][Si:25]([CH2:30][CH3:31])([CH2:28][CH3:29])[CH2:26][CH3:27])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][C:7]1[C:6]2[C:10](=[C:2]([O:1][C@H:55]([CH3:64])[C:56]([N:58]3[CH2:63][CH2:62][O:61][CH2:60][CH2:59]3)=[O:57])[CH:3]=[CH:4][CH:5]=2)[NH:9][CH:8]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium Carbonate2×HCID 11077877HCID 11077877, compound2×HCID 86604028HCID 86604028, compound

Product 1

HCID 86604030HCID 86604030, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl (1R)-2-(7-hydroxy-1H-indol-3-yl)-1-methylethyl((2R)-2-pyridin-3-yl-2-((triethylsilyl)oxy)ethyl)carbamate (300 mg, 0.570 mmol) in N,N-dimethylformamide-(1.0 mL) are added potassium carbonate (98.5 mg, 0.714 mmol), (1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl 4-methylbenzenesulfonate (JP-A-2000-273085) (196 mg, 0.627 mmol), and the mixture is stirred at 50° C. for one hour. To the reaction solution are added potassium carbonate (45 mg), (1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl 4-methylbenzene-sulfonate (120 mg), and the mixture is stirred at 60° C. for 10 hours. After allowed to cool, to the reaction solution is added ethyl acetate (50 mL), and the mixture is filtered, washed with water and a saturated brine, and dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (chloroform/methanol=100/1→20/1) to give tert-butyl (1R)-1-methyl-2-(7-(((1R)-1-methyl-2-morpholin-4-yl-2-oxo-ethyl)oxy)-1H-indol-3-yl)ethyl((2R)-2-pyridin-3-yl-2-((triethylsilyl)oxy)-ethyl)carbamate (209 mg, yield: 55%).

Workup

  1. stirringthe mixture is stirred at 60° C. for 10 hours
  2. temperatureto cool, to the reaction solution
  3. filtrationthe mixture is filtered
  4. washwashed with water
  5. dry with materiala saturated brine, and dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by silica gel column chromatography (chloroform/methanol=100/1→20/1)

Sources & evidence

ORD record
ord-297a5913a46c418fb987fb0a0a77e608
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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