Dimethylformamide → {3-[(2R)-2-((2R)-2-hydroxy-2-pyridin-3-ylethylamino) propyl]-1H-indol-7-yloxy}-acetic acid 1-(cyclohexyloxycarbonyloxy)ethyl ester

HRID 1351953Notes

Reaction equation

HRID 1351953 reaction equation
[OH:1][C@H:2]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[CH2:3][NH:4][C@H:5]([CH3:21])[CH2:6][C:7]1[C:15]2[C:10](=[C:11]([O:16][CH2:17][C:18]([OH:20])=[O:19])[CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1.[C:28](=O)([O-])[O-].[K+].[K+].CN(C)[CH:36]=[O:37].[C:39](=O)([O-:50])[O:40][C:41]1(C(I)C)[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1>[Cl-].[Na+].O>[CH:41]1([O:40][C:39]([O:37][CH:36]([O:19][C:18](=[O:20])[CH2:17][O:16][C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:10]=2[NH:9][CH:8]=[C:7]3[CH2:6][C@H:5]([NH:4][CH2:3][C@H:2]([OH:1])[C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH3:21])[CH3:28])=[O:50])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 9848117{3-[(2R)-2-((2R)-2-Hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetic acidHCID 866040261-Iodoethylcyclohexyl carbonate

Product 1

HCID 69459786{3-[(2R)-2-((2R)-2-hydroxy-2-pyridin-3-ylethylamino) propyl]-1H-indol-7-yloxy}-acetic acid 1-(cyclohexyloxycarbonyloxy)ethyl esterYield 17%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

{3-[(2R)-2-((2R)-2-Hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetic acid (4 mg, 0.011 mmol) and potassium carbonate (3 mg, 0.022 mmol) are added to N,N-dimethylformamide (2 mL), and to the mixture is added at 0° C. 1-iodoethylcyclohexyl carbonate (J. Antibiot., vol. 40, no. 1, p. 81–90 (1987)) (7.8 mg, 0.026 mmol). The mixture is stirred at 0° C. for 2 hours, and thereto is added a saturated brine. The mixture is extracted with ethyl acetate, and the organic layer is washed with a saturated brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel column chromatography (methanol/chloroform=1/20 to 1/1) to give the desired {3-[(2R)-2-((2R)-2-hydroxy-2-pyridin-3-ylethylamino) propyl]-1H-indol-7-yloxy}-acetic acid 1-(cyclohexyloxycarbonyloxy)ethyl ester (1 mg, yield: 17%).

Workup

  1. additionto the mixture is added at 0° C
  2. extractionThe mixture is extracted with ethyl acetate
  3. washthe organic layer is washed with a saturated brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel column chromatography (methanol/chloroform=1/20 to 1/1)

Sources & evidence

ORD record
ord-a5e76defb77440e8b156f0c551d379b2
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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