Water → HCID 58173142, compound

HRID 1517524Notes

Reaction equation

HRID 1517524 reaction equation
C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][CH2:13][C@H:14]2[N:17]([CH3:19])[CH3:18])=[CH:10][CH:9]=1.O.[CH3:21][N:22]1[C:26]([CH3:27])=[C:25](B2OC(C)(C)C(C)(C)O2)[C:24]([CH3:37])=[N:23]1>COCCOC.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>[CH3:18][N:17]([CH3:19])[C@H:14]1[C:15]2[C:11](=[CH:10][CH:9]=[C:8]([C:25]3[C:24]([CH3:37])=[N:23][N:22]([CH3:21])[C:26]=3[CH3:27])[CH:16]=2)[CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27953111,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58173145HCID 58173145, compound

Product 1

HCID 58173142HCID 58173142, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

(Method 1): To a solution of K2CO3 (1.9 mmol) and (R)-(6-bromo-indan-1-yl)-dimethyl-amine (1 mmol) in 1,2-dimethoxyethane (8.8 mL)/water (1.2 mL) was added Pd(PPh3)4 (0.1 mmol) and 1,3,5-trimethyl-1H-pyrazole-4-boronic acid pinacol ester (1.2 mmol). The reaction mixture was degassed and stirred at 85° C. for 6 h. The solvent was evaporated, crude was redissolved in dichloromethane and filtered through a pad of Celite. The filtrate was extracted with 6M HCl (3×0.16 mL). The aqueous layer was basified with 6M NaOH to pH 13 and extracted with dichloromethane. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Crude was purified by flash chromatography (CH2Cl2-MeOH-NEt3 as eluents) to yield (1R)-dimethyl-[6-(1,3,5-trimethyl-1H-pyrazol-4-yl)-indan-1-yl]-amine as an oil (52% yield). Product was obtained with a final ee of 99.6% (determined by chiral HPLC).

Workup

  1. customThe reaction mixture was degassed
  2. customThe solvent was evaporated
  3. dissolutioncrude was redissolved in dichloromethane
  4. filtrationfiltered through a pad of Celite
  5. extractionThe filtrate was extracted with 6M HCl (3×0.16 mL)
  6. extractionextracted with dichloromethane
  7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customCrude was purified by flash chromatography (CH2Cl2-MeOH-NEt3 as eluents)

Sources & evidence

ORD record
ord-f189efe8a6114c818acfb948ea378fc9
Source dataset
uspto-grants-2012_07
Patent number
US08232307B2

Reaction notes

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