Hydrochloric Acid → HCID 59395032, compound

HRID 1465065Notes

Reaction equation

HRID 1465065 reaction equation
[N+:1]([C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:5]=1[C:13]([OH:22])([C:18]([F:21])([F:20])[F:19])[C:14](OC)=[O:15])([O-])=O.Cl>C(OCC)(=O)C.C1COCC1.[Pd]>[NH2:10][C:8]1[CH:9]=[C:4]2[C:5]([C:13]([OH:22])([C:18]([F:21])([F:20])[F:19])[C:14](=[O:15])[NH:1]2)=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 86643090Methyl α-hydroxy-2,4-dinitro-α-(trifluoromethyl)benzeneacetate

Product 1

HCID 59395032HCID 59395032, compoundYield 6.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of methyl 2-(2,4-dinitrophenyl)-3,3,3-trifluoro-2-hydroxypropanoate (1.3 g, 4.01 mmol) in ethyl acetate (18 mL) was added pH3 HCl (5.2 mL) followed by 10% Pd/C (350 mg) in ethyl acetate (3 mL). The mixture was stirred overnight under an atmosphere of H2. The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated in vacuo. The crude residue obtained was partitioned between, dichloromethane (25 mL) and aqueous saturated NaHCO3 (15 mL). The organic phase was separated and the aqueous phase was extracted dichloromethane (2×25 mL). The organic phases were combined, dried over Na2SO4, filtered, and concentrated. Purification by silica gel chromatography (50-100% ethyl acetate/hexanes) provided 6-amino-3-hydroxy-3-(trifluoromethyl)indolin-2-one (921 mg, 99%) To a solution of 6-amino-3-hydroxy-3-(trifluoromethyl)indolin-2-one (58 mg, 0.25 mmol) in THF (0.5 mL) at 0° C. was added BH3.THF complex (1 M in THF, 1 mL, 0.95 mmol) dropwise. The mixture was stirred for 5 min at 0° C. then for 3 h at room temperature. The reaction was quenched by adding very carefully 6M HCl (3.5 mL) until no more gas release was observed. The mixture was then stirred at 80° C. for 2 h. The solvent was removed under reduce pressure and the solid residue obtained was dissolved in DMF (3 mL), filtered and purified by reverse phase HPLC (10-99% CH3CN/H2O) to provide 3-(trifluoromethyl)-1H-indol-6-amine (30 mg, 54%, TFA salt).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe crude residue obtained
  4. customwas partitioned between, dichloromethane (25 mL) and aqueous saturated NaHCO3 (15 mL)
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted dichloromethane (2×25 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography (50-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1715c1de5fef4166a9c3f8283aa0eea5
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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