Methylamine → HCID 16067550, compound

HRID 2246741Notes

Reaction equation

HRID 2246741 reaction equation
Cl[CH2:2][CH2:3][C@@H:4]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH3:21])([CH3:20])[C:12]1=[O:22])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:23][NH2:24]>>[CH3:20][C:13]1([CH3:21])[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]([C@@H:4]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:3][CH2:2][NH:24][CH3:23])[C:12]1=[O:22]

Participants

3

Reactant 2

HCID 6329MethylamineHCID 68523774HCID 68523774, compound

Product 1

HCID 16067550HCID 16067550, compoundYield 93%

Conditions

Temperature
125 °C

Procedure

A mixture of 1-[(1R)-3-chloro-1-phenylpropyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one (220 mg, 0.700 mmol) and ethanolic solution of methylamine (33% in ethanol, 5 mL) was heated at 125° C. for 2 h with stirring in a sealed reaction vessel. Upon cooling, all volatiles were removed under reduced pressure. The resulting residue was dissolved in dichloromethane (20 mL), washed with aqueous potassium carbonate (5 mL), dried (anhydrous sodium sulfate), and concentrated. Purification by Isco CombiFlash Companion chromatography (RediSep 4-g silica column, 0-15% methanol/dichloromethane/0.5% triethylamine) gave 200 mg (93%) of 3,3-dimethyl-1-[(1R)-3-(methylamino)-1-phenylpropyl]-1,3-dihydro-2H-indol-2-one as a viscous colorless liquid, which was dissolved dichloromethane (5 mL) and treated with an ethereal solution of hydrochloric acid (1 M, 0.7 mL, 0.7 mmol). To the resulting solution was added hexane until white powder formed, which was collected, washed with hexane, and dried in vacuo to yield 3,3-dimethyl-1-[(1R)-3-(methylamino)-1-phenylpropyl]-1,3-dihydro-2H-indol-2-one hydrochloride as a white powder. MS (ES) m/z 308.9 ([M+H]+); HRMS: calculated for C20H24N2O+H+, 309.1961; found (ESI, [M+H]+), 309.1953.

Workup

  1. temperatureUpon cooling
  2. customall volatiles were removed under reduced pressure
  3. dissolutionThe resulting residue was dissolved in dichloromethane (20 mL)
  4. washwashed with aqueous potassium carbonate (5 mL)
  5. dry with materialdried (anhydrous sodium sulfate)
  6. concentrationconcentrated
  7. customPurification by Isco CombiFlash Companion chromatography (RediSep 4-g silica column, 0-15% methanol/dichloromethane/0.5% triethylamine)

Sources & evidence

ORD record
ord-2bcc23539ecd41519e0b87f32bfdf30f
Source dataset
uspto-grants-2010_03
Patent number
US07687529B2

Reaction notes

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