Triethylamine → (2S, 3S)-2-amino-N-(2-fluoro-4-trimethylsilanylethynyl-phenyl)-3-phenyl-butyramide

HRID 1433792Notes

Reaction equation

HRID 1433792 reaction equation
[NH2:1][C@@H:2]([C@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][C:7]=1[F:13])=[O:4].C(N(CC)CC)C.[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31]>C(OCC)C.[Cu](I)I>[NH2:1][C@@H:2]([C@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])=[CH:8][C:7]=1[F:13])=[O:4]

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 66111TrimethylsilylacetyleneHCID 68618997(2S,3S)-2-amino-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramide

Product 1

HCID 69007467(2S, 3S)-2-amino-N-(2-fluoro-4-trimethylsilanylethynyl-phenyl)-3-phenyl-butyramideYield 66%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 3283Diethyl EtherSolvent

Procedure

A solution of (2S,3S)-2-amino-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramide (1.00 g, 2.51 mmol) in triethylamine (1.5 mL, 10.8 mmol) was thoroughly degassed with argon, bis-dichlorotriphenylphosphine palladium(II) (20.3 mg, 0.05 mmol) added followed by copper iodide (9.8 mg, 0.05 mmol) and trimethylsilylacetylene (277 mg, 2.77 mmol) and the mixture stirred under argon at ambient temperature for 3 hours. Additional triethylamine (1.5 mL, 10.8 mmol) was added to form a stirrable reaction mixture and stirring continued for an additional 20 hours. The reaction mixture was diluted with diethyl ether and a small amount of Celite added prior to filtration through Celite. The Celite was eluted with diethyl ether (4×20 mL) and the combined organic filtrates concentrated in vacuo. The resulting green oil was dissolved in a small amount of diethyl ether and diluted with hexanes (10 mL) to induce crystallization. The product was isolated by filtration, washed with hexanes and dried in vacuo to afford (2S,3S)-2-amino-N-(2-fluoro-4-trimethylsilanylethynyl-phenyl)-3-phenyl-butyramide as a grey solid (610 mg, 66%). A second crop of product was obtained by reprocessing of the mother liquors from the initial crystallization (168 mg, 18%).

Workup

  1. additionadded
  2. customto form
  3. customa stirrable reaction mixture
  4. stirringstirring
  5. waitcontinued for an additional 20 hours
  6. additiona small amount of Celite added
  7. filtrationto filtration through Celite
  8. washThe Celite was eluted with diethyl ether (4×20 mL)
  9. concentrationthe combined organic filtrates concentrated in vacuo
  10. dissolutionThe resulting green oil was dissolved in a small amount of diethyl ether
  11. additiondiluted with hexanes (10 mL)
  12. customcrystallization
  13. customThe product was isolated by filtration
  14. washwashed with hexanes
  15. customdried in vacuo

Sources & evidence

ORD record
ord-858594f1f93d4c18968cd43aca07841d
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

Loading…