Sodium borohydride → isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)amino)phenoxy)acetate

HRID 1051094Notes

Reaction equation

HRID 1051094 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][CH2:13][C:14]3=O)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:18][C:19]1[CH:20]=[C:21]([CH:30]=[CH:31][CH:32]=1)[O:22][CH2:23][C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25].[BH4-].[Na+]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][CH2:13][CH:14]3[NH:18][C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][CH:32]=3)[O:22][CH2:23][C:24]([O:26][CH:27]([CH3:28])[CH3:29])=[O:25])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 10608474Isopropyl 2-(3-aminophenoxy)acetateHCID 820809706-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-one

Product 1

HCID 118161547isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)amino)phenoxy)acetateYield 20.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Approximately forty oven dried 3 Å molecular sieves were added to a solution of 6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-one (66 mg, 0.292 mmol) and isopropyl 2-(3-aminophenoxyl)acetate (122 mg, 0.583 mmol) in toluene (3 mL) at room temperature. The reaction was heated in a 120° C. oil bath and allowed to stir overnight for approximately 16 hours. The reaction was cooled to room temperature and sodium borohydride (44 mg, 1.2 mmol) was added. The solution was stirred for 4 hours at room temperature. The reaction was quenched with saturated aqueous NaHCO3 (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The resulting crude residue was purified by combiflash (12 g column, hexanes→100% ethyl acetate/hexanes, gradient) to afford 25 mg (20%) of isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)amino)phenoxy)acetate.

Workup

  1. customApproximately forty oven dried 3 Å molecular sieves
  2. temperatureThe reaction was cooled to room temperature
  3. stirringThe solution was stirred for 4 hours at room temperature
  4. customThe reaction was quenched with saturated aqueous NaHCO3 (50 mL)
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting crude residue was purified by combiflash (12 g column, hexanes→100% ethyl acetate/hexanes, gradient)

Sources & evidence

ORD record
ord-a44c736568c84ba291d7837e056acb69
Source dataset
uspto-grants-2016_07
Patent number
US09388153B2

Reaction notes

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