Pyridine → HCID 57636298, compound

HRID 2110360Notes

Reaction equation

HRID 2110360 reaction equation
[OH:1][C@H:2]([CH2:25]O)[C@@H:3]([N:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]2([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:11]1=[O:24])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[N:38]1C=CC=C[CH:39]=1>C(OCC)(=O)C>[OH:1][C@H:2]([CH2:25][NH:38][CH3:39])[C@@H:3]([N:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]2([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:11]1=[O:24])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 73974-Toluenesulfonyl chlorideHCID 68904334HCID 68904334, compound

Product 1

HCID 57636298HCID 57636298, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1′-[(1S,2S)-2,3-dihydroxy-1-phenyl-propyl]spiro[cyclohexane-1,3′-indol]-2′(1′H)-one (250 mg, 0.71 mmol) was dissolved in pyridine (2.5 mL) and para-toluenesulfonyl chloride (169 mg, 0.89 mmol) was added. The reaction was stirred for 5 hours, then the reaction mixture was diluted with ethyl acetate and washed with water, a saturated aqueous solution of copper sulfate, a 2N aqueous solution of 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 solution in ethanol, 15 mL) and stirred for 16 hours. The mixture was concentrated in vacuo and purified via flash column chromatography (silica, 5% methanol saturated with ammonia in chloroform) to give 85 mg (32%) 1′-[(1S,2R)-2-hydroxy-3-(methylamino)-1-phenylpropyl]spiro[cyclo-hexane-1,3′-indol]-2′(1′H)-one as a colorless oil. The freebase was dissolved in diethyl ether (5 mL) and treated with a 1 N ethereal solution of hydrochloric acid (0.23 mL, 0.23 mmol, 1 equivalent). The white precipitate was collected and dried under vacuum to give 193 mg (60%) of 1′-[(1S,2R)-2-hydroxy-3-(methylamino)-1-phenylpropyl]spiro[cyclo-hexane-1,3′-indol]-2′(1′H)-one hydrochloride. HRMS: calcd for C23H28N2O2+H+, 365.22235; found ([M+H]+), 365.2226;

Workup

  1. washwashed with water
  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 solution in ethanol, 15 mL)
  7. stirringstirred for 16 hours
  8. concentrationThe mixture was concentrated in vacuo
  9. custompurified via flash column chromatography (silica, 5% methanol saturated with ammonia in chloroform)

Sources & evidence

ORD record
ord-3a5573c68eb74cfd837130cc79ce3420
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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