Hexamethyldisilazane → HCID 18626624, compound

HRID 1860203Notes

Reaction equation

HRID 1860203 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14](O)=[O:15])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:11])=[O:10])#[N:2].C(Cl)(=O)C(Cl)=O.C[Si](C)(C)[NH:31][Si](C)(C)C>C(Cl)Cl.CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14]([NH2:31])=[O:15])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:11])=[O:10])#[N:2]

Participants

6

Reactant 3

HCID 13838HexamethyldisilazaneHCID 65578Oxalyl chlorideHCID 120694992-(3-Cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 18626624HCID 18626624, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (200 mg, 0.62 mmol) in methylene chloride (2 mL) cooled to 0° C. was treated with N,N-dimethylformamide (2 drops). The reaction mixture was then slowly treated with oxalyl chloride (60 μL, 0.69 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 1.5 h. The resulting reaction mixture was then treated dropwise with 1,1,1,3,3,3-hexamethyldisilazane (395 μL, 1.87 mmol) and subsequently stirred at 25° C. for 15 h. The reaction mixture was then partitioned between methylene chloride (20 mL), methanol (15 mL), and a 5% aqueous sulfuric acid solution (25 mL). The organic layer was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/3 hexanes/ethyl acetate) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (141 mg, 70%) as a white foam: mp 67-70° C. (foam to gel); EI-HRMS m/e calcd for C16H20N2O3S (M+) 320.1195, found 320.1195.

Workup

  1. stirringstirred at 25° C. for 1.5 h
  2. customThe resulting reaction mixture
  3. stirringsubsequently stirred at 25° C. for 15 h
  4. customThe reaction mixture was then partitioned between methylene chloride (20 mL), methanol (15 mL)
  5. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-82c1f9cda56f4571853891e9503376df
Source dataset
uspto-grants-2003_03
Patent number
US06528543B1

Reaction notes

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