Triethylamine → tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]hex-5-enoate

HRID 1700972Notes

Reaction equation

HRID 1700972 reaction equation
CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:23][C:24]([CH3:53])([CH3:52])[C@H:25]([NH:37][C:38]([C@H:40]([CH2:49][CH:50]=[CH2:51])[CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[O:39])[C:26]([NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:27].[CH3:54][C:55]1[CH:56]=[C:57](Br)[CH:58]=[CH:59][C:60]=1[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:53][C:24]([CH3:52])([CH3:23])[C@H:25]([NH:37][C:38]([C@H:40]([CH2:49]/[CH:50]=[CH:51]/[C:57]1[CH:58]=[CH:59][C:60]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[C:55]([CH3:54])[CH:56]=1)[CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[O:39])[C:26]([NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 99648454-Bromo-2-methylbiphenylHCID 54508002tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)hex-5-enoate

Product 1

HCID 59875726tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]hex-5-enoateYield 69%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×

Procedure

A mixture of palladium acetate (52 mg, 0.23 mmol) and tri-(2-methylphenyl)phosphine (141 mg, 0.46 mmol) in anhydrous acetonitrile (10 mL) was sonicated at room temperature for 1 min until a creamy-coloured suspension formed. This suspension was added via Pasteur pipette to a stirred solution of tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)hex-5-enoate (Preparation 2)(861 mg, 2.0 mmol), 3-methyl-4-phenylbromobenzene (M. Gomberg, J. C. Pernert, J. Amer. Chem. Soc., 1926, 48, 1372-84, and see also Preparation 19B)(1.32 gm, 5.34 mmol), and triethylamine (1.28 mL, 9.29 mmol) in anhydrous acetonitrile (15 mL) under nitrogen. The mixture was purged with nitrogen, then heated at reflux for 24 h. The mixture was poured into ethyl acetate (200 mL) and washed with saturated aqueous sodium chloride (2×100 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with dichloromethane:ethyl acetate) to give mainly tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]hex-5-enoate as a colourless foam (1.91 gm, 69%). 1H NMR suggests that two alkene isomers, the (5Z) and (4E) were also present. The mixture of alkenes was taken onto the next step (see b, below).

Workup

  1. customwas sonicated at room temperature for 1 min until a creamy-coloured suspension
  2. customformed
  3. customThe mixture was purged with nitrogen
  4. temperatureheated
  5. temperatureat reflux for 24 h
  6. additionThe mixture was poured into ethyl acetate (200 mL)
  7. washwashed with saturated aqueous sodium chloride (2×100 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography (gradient elution with dichloromethane:ethyl acetate)

Sources & evidence

ORD record
ord-e3ba1e4f44df4cbba295365ced277786
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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