Toluene → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1 (S),2-dihydroxy-2-methyl-propyl)-pyrazin-2-yl]-propionamide

HRID 719977Notes

Reaction equation

HRID 719977 reaction equation
[C:1](=[O:4])([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:18]([CH2:32][CH:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)[C:19]([NH:21][C:22]2[CH:27]=[N:26][C:25](C=C(C)C)=[CH:24][N:23]=2)=[O:20])[CH:11]=[CH:12][C:13]=1[S:14]([CH3:17])(=[O:16])=[O:15].CS(N)(=O)=O.S([O-])([O-])=[O:44].[Na+].[Na+].[C:49]1([CH3:55])C=CC=C[CH:50]=1>C(OCC)(=O)C.[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[Os](=O)(=O)(=O)=O.CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.O.C(O)(C)(C)C>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:18]([CH2:32][CH:33]2[CH2:34][CH2:35][CH2:36][CH2:37]2)[C:19]([NH:21][C:22]2[CH:27]=[N:26][C:25]([C@H:1]([OH:4])[C:49]([OH:44])([CH3:55])[CH3:50])=[CH:24][N:23]=2)=[O:20])[CH:11]=[CH:12][C:13]=1[S:14]([CH3:17])(=[O:16])=[O:15]

Participants

11

Reactant 5

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 24437Sodium SulfiteHCID 72879MethanesulfonamideHCID 674827762(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-methylpropenyl)-pyrazin-2-yl]-propionamide

Product 1

HCID 104134752(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1 (S),2-dihydroxy-2-methyl-propyl)-pyrazin-2-yl]-propionamideYield 69%

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineCatalystHCID 178511488HCID 178511488, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Conditions

Temperature
25 °C

Procedure

A mixture of potassium ferricyanide (738 mg, 2.24 mmol), potassium carbonate (310 mg, 2.24 mmol), and (DHQ)2PHAL (11.7 mg, 0.015 mmol) was treated with a solution of water/tert-butyl alcohol (15 mL, 1:1) and stirred at 25° C. to give a clear solution. The reaction mixture was then treated with a 0.2M solution of osmium tetroxide in toluene (37.4 μL). The reaction mixture was cooled to 0° C. and then was treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-methylpropenyl)-pyrazin-2-yl]-propionamide (345 mg, 0.748 mmol) followed by the addition of methane sulfonamide (71 mg, 0.747 mmol). The mixture was stirred at 0° C. for 18 h until all the olefin was reacted. The mixture was diluted with ethyl acetate (30 mL) and treated with sodium sulfite (1.0 g). The solution was extracted with ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/5 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1(S),2-dihydroxy-2-methyl-propyl)-pyrazin-2-yl]-propionamide (255 mg, 69%) as an off-white foam: (ES)+-HRMS m/e calcd for C23H30ClN3O5S (M+H)+ 496.1668, found 496.1657.

Workup

  1. customto give a clear solution
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customwas reacted
  4. extractionThe solution was extracted with ethyl acetate and water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2b157337404347a6b4bb43115230e3fb
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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