Hydrochloric Acid → 3-(2-hydroxy-4-methoxy-5-(1-methyl-1H-indazol-5-yl)phenyl)propanoic acid

HRID 2194947Notes

Reaction equation

HRID 2194947 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[O:8][C:7](=[O:14])[CH2:6][CH2:5]2.[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][C:21](B(O)O)=[CH:22][CH:23]=2)[CH:18]=[N:17]1.C(=O)([O-])[O-:29].[K+].[K+].[OH-].[Na+].Cl>C(COC)OC.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.O>[OH:8][C:9]1[CH:10]=[C:11]([O:12][CH3:13])[C:2]([C:21]2[CH:20]=[C:19]3[C:24](=[CH:23][CH:22]=2)[N:16]([CH3:15])[N:17]=[CH:18]3)=[CH:3][C:4]=1[CH2:5][CH2:6][C:7]([OH:14])=[O:29]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 225589101-Methyl-1H-indazole-5-boronic acidHCID 668766776-Bromo-7-methoxychroman-2-one

Product 1

HCID 444627473-(2-hydroxy-4-methoxy-5-(1-methyl-1H-indazol-5-yl)phenyl)propanoic acidYield 61.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of Intermediate 3 (4.2 g) in dimethoxyethane (50 ml) was added with 1-methyl-1H-indazol-5-ylboronic acid (rgt1, 4.3 g), potassium carbonate (4.5 g), water (50 ml), and tetrakistriphenylphosphinepalladium(0) [henceforth abbreviated as Pd(PPh3)4] (2.7 g, Nacarai), and stirred at 90° C. for 14 hours. This reaction mixture was added with 2 N aqueous sodium hydroxide (5 ml), and further stirred at 80° C. for 0.5 hour. The reaction mixture was added with 1 N aqueous hydrochloric acid (10 ml), and extracted with diethyl ether (30 ml×2), and then the aqueous layer was neutralized with 5 N aqueous hydrochloric acid, and extracted with ethyl acetate. The reaction mixture was washed with saturated aqueous sodium hydrogencarbonate, the organic layer was dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (3.3 g).

Workup

  1. stirringfurther stirred at 80° C. for 0.5 hour
  2. extractionextracted with diethyl ether (30 ml×2)
  3. extractionextracted with ethyl acetate
  4. washThe reaction mixture was washed with saturated aqueous sodium hydrogencarbonate
  5. customthe organic layer was dried
  6. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-66ffef2649ea4307b767647faf75e272
Source dataset
uspto-grants-2012_12
Patent number
US08334314B2

Reaction notes

Loading…