Pyridine → HCID 16067550, compound

HRID 2246739Notes

Reaction equation

HRID 2246739 reaction equation
O[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.C1(C)C(S(Cl)(=O)=O)=CC=CC=1.[N:34]1C=CC=C[CH:35]=1>C(OCC)(=O)C.CN>[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:34][CH3:35])[C:12]1=[O:22]

Participants

6

Reactant 3

HCID 1049PyridineHCID 8623o-Toluenesulfonyl chlorideHCID 58838562HCID 58838562, compound

Product 1

HCID 16067550HCID 16067550, compound

Reagents, catalysts & solvents 2

HCID 6329MethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-[(1S)-3-hydroxy-1-phenylpropyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one (1.2 g, 4.1 mmol) was dissolved in pyridine (5 mL) and toluenesufonyl chloride (0.84 g, 4.4 mmol) was added. Stirred for 16 hours then the reaction mixture was diluted with ethyl acetate and washed with water, 2N hydrochloric acid, saturated copper sulfate, 2N hydrochloric acid, and saturated brine. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. A portion of the crude product (100 mg, 0.21 mmol) was immediately dissolved in methylamine (8M in ethanol, 10 mL) and stirred for 16 hours. The mixture was concentrated in vacuo and purified via chromatography (silica, 0-15% methanol saturated with ammonia in chloroform) to give 3,3-dimethyl-1-[(1R)-3-(methylamino)-1-phenylpropyl]-1,3-dihydro-2H-indol-2-one as a colorless oil. The freebase was dissolved in ether (5 mL) and treated with 1N hydrochloric acid in ether (1.0 equivalent). The white precipitate was collected and dried under vacuum to give 44 mg 3,3-dimethyl-1-[(1R)-3-(methylamino)-1-phenylpropyl]-1,3-dihydro-2H-indol-2-one hydrochloride.

Workup

  1. washwashed with water, 2N hydrochloric acid, saturated copper sulfate, 2N hydrochloric acid, and saturated brine
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringstirred for 16 hours
  7. concentrationThe mixture was concentrated in vacuo
  8. custompurified via chromatography (silica, 0-15% methanol saturated with ammonia in chloroform)

Sources & evidence

ORD record
ord-b78f743b3a5549a4a8e997008926a64b
Source dataset
uspto-grants-2010_03
Patent number
US07687529B2

Reaction notes

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