Dimethylformamide → 6-Chloro-2-(5-hydroxy-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester

HRID 593609Notes

Reaction equation

HRID 593609 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7](B(O)O)[N:8]2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:4][CH:3]=1.[OH:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26](Br)[CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C=O)C>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]([O:13][C:11]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)[CH:6]=[C:7]1[C:26]1[CH:25]=[N:24][CH:23]=[C:22]([OH:21])[CH:27]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 5995293-Bromo-5-hydroxypyridineHCID 441191511-Boc-6-chloroindole-2-boronic acid

Product 1

HCID 582155456-Chloro-2-(5-hydroxy-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A microwave flask is charged with 6-chloro-1-Boc-indole-2-boronic acid (1.91 g, 6.46 mmol), 3-hydroxy-5-bromopyridine (0.750 g, 4.31 mmol), potassium phosphate (1.83 g, 8.62 mmol) and DMF (15 mL). The flask is evacuated and filled with nitrogen thrice and Pd(PPh3)4 (0.250 g, 0.215 mmol) is added. The flask is evacuated and filled with nitrogen thrice again, and heated to 110° C. under microwave irradiation for 45 min. Pd(PPh3)4 (0.100 g, 0.086 mmol) is added and the vial is heated again to 110° C. under microwave irradiation for 45 min. The mixture is then diluted with ethyl acetate and washed with water thrice. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by silica gel flash chromatography (dichloromethane-methanol, 19:1) to afford 6-chloro-2-(5-hydroxy-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester as a solid. MS (ESI) m/z 345.06 (M+H)+

Workup

  1. customThe flask is evacuated
  2. additionis added
  3. customThe flask is evacuated
  4. additionfilled with nitrogen thrice again
  5. temperaturethe vial is heated again to 110° C. under microwave irradiation for 45 min
  6. washwashed with water thrice
  7. dry with materialThe organic layer is dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by silica gel flash chromatography (dichloromethane-methanol, 19:1)

Sources & evidence

ORD record
ord-2a629978482141739cf6fcf6bde54850
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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