Hydrochloric Acid → HCID 58838563, compound

HRID 2246742Notes

Reaction equation

HRID 2246742 reaction equation
Cl.[CH3:2][C:3]1([CH3:24])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C@@H:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13][CH2:14][NH:15][CH3:16])[C:4]1=O.B.Cl>O1CCCC1>[CH3:2][C:3]1([CH3:24])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C@@H:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13][CH2:14][NH:15][CH3:16])[CH2:4]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 68526588HCID 68526588, compound

Product 1

HCID 58838563HCID 58838563, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3,3-dimethyl-1-[(1R)-3-(methylamino)-1-phenylpropyl]-1,3-dihydro-2H-indol-2-one (Example 9, Step 2, 150 mg, 0.486 mmol) in dry tetrahydrofuran (3 mL) under nitrogen was added dropwise a solution of borane (1.0 M in tetrahydrofuran, 1.0 mL, 1.0 mmol, 2 equiv.) via a syringe. The resulting solution was heated at 70° C. with stirring for 2 h. Upon cooling, the reaction mixture was treated dropwise with a 2N aqueous solution of hydrochloric acid (2 mL), and was again heated at 60° C. for 20 minutes Upon cooling, solvent was removed under reduced pressure. To the residue was slowly added aqueous potassium carbonate (5 mL), and the mixture was extracted with dichloromethane (20 mL). The organic layer was washed with brine, 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 100 mg (70%) of (3R)-3-(3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-N-methyl-3-phenylpropan-1-amine as a viscous brown liquid, which was dissolved dichloromethane (3 mL) and treated with an ethereal solution of hydrochloric acid (1 M, 0.37 mL, 0.37 mmol). To the resulting solution was added hexane until white powder formed, which was collected, washed with hexane, and dried in vacuo to yield (3R)-3-(3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-N-methyl-3-phenylpropan-1-amine hydrochloride as a yellow powder. MS (ES) m/z 295.3 ([M+H]+); HRMS: calculated for C20H26N2+H+, 295.2169; found (ESI, [M+H]+), 295.2160.

Workup

  1. temperatureUpon cooling
  2. temperaturewas again heated at 60° C. for 20 minutes
  3. temperatureUpon cooling
  4. customsolvent was removed under reduced pressure
  5. extractionthe mixture was extracted with dichloromethane (20 mL)
  6. washThe organic layer was washed with brine
  7. dry with materialdried (anhydrous sodium sulfate)
  8. concentrationconcentrated
  9. customPurification by Isco CombiFlash Companion chromatography (RediSep 4-g silica column, 0-15% methanol/dichloromethane/0.5% triethylamine)

Sources & evidence

ORD record
ord-6edc1e4f3bfc4c5cb93de5d6aeaa7cc7
Source dataset
uspto-grants-2010_03
Patent number
US07687529B2

Reaction notes

Loading…