N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide → 3-cyclopentyl-N-[5-(1-hydroxyimino-ethyl)-pyrazin-2-yl]-2(R)-(4-methanesulfonyl-phenyl)-propionamide

HRID 719917Notes

Reaction equation

HRID 719917 reaction equation
C([O:5][N:6]=[C:7]([C:9]1[N:10]=[CH:11][C:12]([NH:15][C:16](=[O:34])[C@@H:17]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=2)[CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[N:13][CH:14]=1)[CH3:8])(C)(C)C>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH:19]1([CH2:18][C@H:17]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][CH:25]=2)[C:16]([NH:15][C:12]2[CH:11]=[N:10][C:9]([C:7](=[N:6][OH:5])[CH3:8])=[CH:14][N:13]=2)=[O:34])[CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

4

Reactant 1

HCID 86593788N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide

Product 1

HCID 1363347563-cyclopentyl-N-[5-(1-hydroxyimino-ethyl)-pyrazin-2-yl]-2(R)-(4-methanesulfonyl-phenyl)-propionamideYield 91.2%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide (342.6 mg, 0.704 mmol) in methylene chloride (1.4 mL) was cooled to 0° C. and then was treated with a 1.0M solution of titanium tetrachloride in methylene chloride (2.10 mL, 2.10 mmol). The resulting reaction solution was stirred at 0° C. for 2 h and then was stirred at 25° C. for 1 h 50 min. The reaction solution was concentrated in vacuo and then partitioned between ethyl acetate (210 mL) and water (150 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (150 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 3/2 ethyl acetate/hexanes) afforded the 3-cyclopentyl-N-[5-(1-hydroxyimino-ethyl)-pyrazin-2-yl]-2(R)-(4-methanesulfonyl-phenyl)-propionamide (276.3 mg, 91%) as a white foam: mp 118.8–122.4° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H26N4O4S (M+H)+ 431.1748, found 431.1752.

Workup

  1. customThe resulting reaction solution
  2. stirringwas stirred at 25° C. for 1 h 50 min
  3. concentrationThe reaction solution was concentrated in vacuo
  4. custompartitioned between ethyl acetate (210 mL) and water (150 mL)
  5. washThe organic layer was washed with a saturated aqueous sodium chloride solution (150 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5e70782cc2a84949a9d43407fb05611b
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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