Pyridine → HCID 16067546, compound

HRID 2246724Notes

Reaction equation

HRID 2246724 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3([CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:13]2=[O:26])[CH2:9][CH2:10]O)[CH:5]=[CH:6][CH:7]=1.C1(C)C(S(Cl)(=O)=O)=CC=CC=1.[N:38]1C=CC=C[CH:39]=1>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3([CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:13]2=[O:26])[CH2:9][CH2:10][NH:38][CH3:39])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 8623o-Toluenesulfonyl chlorideHCID 68525173HCID 68525173, compound

Product 1

HCID 16067546HCID 16067546, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1′-[(1R)-1-(3-fluorophenyl)-3-hydroxypropyl]spiro [cyclohexane-1,3′-indol]-2′(1′H)-one (0.26 g, 0.74 mmol) was dissolved in pyridine (4 mL) and toluenesufonyl chloride (0.21 g, 1.1 mmol) was added. Stirred for 3 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. The crude product was immediately dissolved in methylamine (8M in ethanol, 30 mL) and stirred for 16 hours. The mixture was concentrated in vacuo and purified via chromatography (silica, 5% methanol saturated with ammonia in chloroform) to give 1′-[(1R)-1-(3-fluorophenyl)-3-(methylamino)propyl]spiro[cyclohexane-1,3′-indol]-2′(1′H)-one as a colorless oil (0.26 g). The freebase was dissolved in ether (5 mL) and treated with 1N hydrochloric acid in ether (0.71 mL, 1.0 equivalent). The white precipitate was collected and dried under vacuum to give 203 mg (51% over three steps) 1′-[(1R)-1-(3-fluorophenyl)-3-(methylamino)propyl]spiro[cyclohexane-1,3′-indol]-2′(1′H)-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. dissolutionThe crude product was immediately dissolved in methylamine (8M in ethanol, 30 mL)
  7. stirringstirred for 16 hours
  8. concentrationThe mixture was concentrated in vacuo
  9. custompurified via chromatography (silica, 5% methanol saturated with ammonia in chloroform)

Sources & evidence

ORD record
ord-a6cc3c5fc22d45418e04215717a20cdb
Source dataset
uspto-grants-2010_03
Patent number
US07687529B2

Reaction notes

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