Sodium borohydride → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-hydroxy-cyclohexyl)-propionamide

HRID 854751Notes

Reaction equation

HRID 854751 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:23][CH:24]2[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([Cl:22])=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[BH4-].[Na+]>CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:23][CH:24]2[CH2:25][CH2:26][CH:27]([OH:30])[CH2:28][CH2:29]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([Cl:22])=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 10412416HCID 10412416, compound

Product 1

HCID 100735202(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-hydroxy-cyclohexyl)-propionamideYield 96.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-oxo-cyclohexyl)-propionamide (prepared as in Example 61, 30.0 mg, 0.064 mmol) in methanol (0.5 mL) was treated with sodium borohydride (6.03 mg, 0.16 mmol). The reaction mixture was stirred at 25° C. for 5 min. The reaction was then diluted with ethyl acetate (5 mL) and quenched by the dropwise addition of water. The reaction was then diluted with more water (5 mL) and concentrated in vacuo to remove methanol. The resulting slurry was extracted with ethyl acetate 3×5 mL), and the combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12S, Silica, 3/7 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-hydroxy-cyclohexyl)-propionamide (29.0 mg, 96.3%) as a light yellow foam: EI-HRMS m/e calcd for C20H23Cl2N3O4S (M+H)+ 472.0859. found 472.0866.

Workup

  1. customquenched by the dropwise addition of water
  2. additionThe reaction was then diluted with more water (5 mL)
  3. concentrationconcentrated in vacuo
  4. customto remove methanol
  5. extractionThe resulting slurry was extracted with ethyl acetate 3×5 mL), and the combined organic extracts
  6. dry with materialwere dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c43a244f3ff446eea16202f742f4c5c5
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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