Diethyl Ether → 1-((2R,4R)-1-(6-(6-ethanesulfonyl-pyridin-3-yloxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl)-4-hydroxy-pyrrolidin-2-yl)-ethanone

HRID 13371Notes

Reaction equation

HRID 13371 reaction equation
C[Li].[CH2:3](OCC)C.CON(C)[C:11]([C@H:13]1[CH2:17][C@@H:16]([OH:18])[CH2:15][N:14]1[C:19]1[C:33]([O:34][C:35]2[CH:36]=[N:37][C:38]([S:41]([CH2:44][CH3:45])(=[O:43])=[O:42])=[CH:39][CH:40]=2)=[CH:32][C:22]2[N:23]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[NH:25][C:21]=2[CH:20]=1)=[O:12].[Cl-].[NH4+]>O1CCCC1>[CH2:44]([S:41]([C:38]1[N:37]=[CH:36][C:35]([O:34][C:33]2[C:19]([N:14]3[CH2:15][C@H:16]([OH:18])[CH2:17][C@@H:13]3[C:11](=[O:12])[CH3:3])=[CH:20][C:21]3[NH:25][C:24]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)=[N:23][C:22]=3[CH:32]=2)=[CH:40][CH:39]=1)(=[O:42])=[O:43])[CH3:45]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 86619211HCID 86619211, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 674828191-((2R,4R)-1-(6-(6-ethanesulfonyl-pyridin-3-yloxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl)-4-hydroxy-pyrrolidin-2-yl)-ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

0.360 ml of methyl lithium (1.0 M diethyl ether solution was added to a tetrahydrofuran (1 ml) solution of 20 mg of (2R,4R)-1-(6-(6-ethanesulfonyl-pyridin-3-yloxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl)-4-hydroxy-pyrrolidin-2-carboxylic acid methoxy-methyl-amide obtained in (step 1), at −78° C. The reaction liquid was stirred at −78° C. for 1 hour, heated up to 0° C. and stirred for 1 hour. Aqueous saturated ammonium chloride solution was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1) to obtain the entitled compound as a pale yellow solid.

Workup

  1. customobtained in (step 1), at −78° C
  2. customThe reaction liquid
  3. temperatureheated up to 0° C.
  4. stirringstirred for 1 hour
  5. extractionextracted with ethyl acetate
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customThe solvent was evaporated away under reduced pressure
  8. customthe resulting residue was purified
  9. customthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-8869583f015c41858b9cecccfa5ea274
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Reaction notes

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