Lithium Hydroxide → HCID 86578773, compound

HRID 1774590Notes

Reaction equation

HRID 1774590 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][CH2:13][CH2:12][C:11]=3[CH:16]=2)=[C:5]([CH:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20]C)=[O:19])[N:4]([CH3:27])[N:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:71]2[CH:75]=[C:74]([CH2:76][CH2:77][CH3:78])[S:73][CH:72]=2)O1.[OH-].[Li+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:23]([O:22][CH:17]([C:5]1[N:4]([CH3:27])[N:3]=[C:2]([C:71]2[CH:75]=[C:74]([CH2:76][CH2:77][CH3:78])[S:73][CH:72]=2)[C:6]=1[C:7]1[CH:8]=[CH:9][C:10]2[O:15][CH2:14][CH2:13][CH2:12][C:11]=2[CH:16]=1)[C:18]([OH:20])=[O:19])([CH3:24])([CH3:26])[CH3:25]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 90092451HCID 90092451, compoundHCID 90095885HCID 90095885, compound

Product 1

HCID 86578773HCID 86578773, compoundYield 78.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a degassed solution of methyl 2-[3-bromo-4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-pyrazol-5-yl]-2-(tert-butoxy)acetate (11i) (50 mg, 0.114 mmol) in dioxane (1 mL) was added Palladium (II) acetate (1.3 mg, 0.006 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (4.7 mg, 0.011 mmol). After stirring for 30 minutes at room temperature, potassium carbonate (47 mg, 0.343 mmol) in solution in water (0.25 mL) and 4,4,5,5-tetramethyl-2-(5-propylthiophen-3-yl)-1,3,2-dioxaborolane (11c) (40 mg, 0.160 mmol) were added and the reaction mixture was heated at 110° C. until consumption of the starting materials. Then lithium hydroxide (11 mg, 0.46 mmol) was added. The heating was maintained until completion of the reaction. The mixture was concentrated in vacuo. Water (2 mL) was added to the residue and the aqueous layer was washed with diethyl ether (2 mL), acidified with 1M hydrochloric acid until pH 3 and extracted with ethyl acetate (2×3 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to provide 2-(tert-butoxy)-2-[4-(3,4-dihyd ro-2H-1-benzopyran-6-yl)-1-methyl-3-(5-propylthiophen-3-yl)-1H-pyrazol-5-yl]acetic acid (example 11) (40 mg, 0.09 mmol, 75%).

Workup

  1. temperaturethe reaction mixture was heated at 110° C. until consumption of the starting materials
  2. temperatureThe heating was maintained until completion of the reaction
  3. concentrationThe mixture was concentrated in vacuo
  4. additionWater (2 mL) was added to the residue
  5. washthe aqueous layer was washed with diethyl ether (2 mL)
  6. extractionextracted with ethyl acetate (2×3 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a9af1426c4bb425db640246ae2341ff1
Source dataset
uspto-grants-2016_02
Patent number
US09260395B2

Reaction notes

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