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

HRID 1700977Notes

Reaction equation

HRID 1700977 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].I[C:55]1[CH:60]=[CH:59][C:58]([O:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[C:57]([CH3:68])[CH:56]=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:55]1[CH:60]=[CH:59][C:58]([O:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[C:57]([CH3:68])[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 183192191-Iodo-3-methyl-4-phenoxybenzeneHCID 54508002tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)hex-5-enoate

Product 1

HCID 59875764tert-butyl (3R,5E)-3-({[(1s)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-(3-methyl-4-phenoxyphenyl)hex-5-enoateYield 81.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of palladium acetate (20 mg, 0.08 mmol) and tri-(2-methylphenyl)phosphine (50 mg, 0.16 mmol) was added 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)(578 mg, 1.23 mmol), 1-iodo-3-methyl-4-phenoxybenzene (Preparation 11)(384 mg, 1.35 mmol), and triethylamine (300 μL, 2.14 mmol) in anhydrous acetonitrile (3 mL) under nitrogen. The mixture was purged with nitrogen, then heated at reflux for 24 h. After being cooled, the mixture was poured into ethyl acetate (100 mL) and washed with saturated aqueous sodium chloride (2×50 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with hexane:ethyl acetate=9:1 and then 4:1) 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-phenoxyphenyl)hex-5-enoate as an orange foam (615 mg). 1H nmr suggested that two alkene isomers, the (5Z) and (4E), together with the alkene starting material (10%) were also present. The mixture of alkenes was taken onto the next step (see b, below).

Workup

  1. customThe mixture was purged with nitrogen
  2. temperatureheated
  3. temperatureat reflux for 24 h
  4. temperatureAfter being cooled
  5. additionthe mixture was poured into ethyl acetate (100 mL)
  6. washwashed with saturated aqueous sodium chloride (2×50 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (
  10. washeluting with hexane

Sources & evidence

ORD record
ord-b146d287a6ae4cbe8c544fb7f768562f
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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