Potassium Phosphate, Tribasic → HCID 86692445, compound

HRID 1748482Notes

Reaction equation

HRID 1748482 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:44]([O:46][C:47]([C:49]1[C:57]2[C:52](=[CH:53][CH:54]=[C:55](Br)[CH:56]=2)[N:51]([CH3:59])[CH:50]=1)=[O:48])[CH3:45]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH2:44]([O:46][C:47]([C:49]1[C:57]2[C:52](=[CH:53][CH:54]=[C:55]([CH:1]3[CH2:3][CH2:2]3)[CH:56]=2)[N:51]([CH3:59])[CH:50]=1)=[O:48])[CH3:45]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86692444HCID 86692444, compound

Product 1

HCID 86692445HCID 86692445, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

Cyclopropylboronic acid (457 mg), palladium (II) acetate (79.5 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (290 mg) and tripotassium phosphate (1.88 g) were added at room temperature to a solution of 5-bromo-1-methyl-1H-indole-3-carboxylic acid ethyl ester (1.0 g) described in Reference Example 52(2) in tetrahydrofuran (14 ml), and the mixture was stirred at 75° C. for five hours. After completion of the reaction, the reaction solution was cooled to room temperature, water was added and filtered through Celite. The filtrate was extracted with ethyl acetate three times. The organic layer was dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 5-cyclopropyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester (802 mg) as a yellow solid.

Workup

  1. customAfter completion of the reaction
  2. temperaturethe reaction solution was cooled to room temperature
  3. filtrationfiltered through Celite
  4. extractionThe filtrate was extracted with ethyl acetate three times
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-4941db06b2884f9c8d66fb3513bbea1c
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

Loading…