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

HRID 1700984Notes

Reaction equation

HRID 1700984 reaction equation
[CH3:1][C:2]([CH3:34])([CH3:33])[C@H:3]([NH:15][C:16]([C@H:18]([CH2:30][CH:31]=[CH2:32])[C@H:19]([CH2:27][CH2:28][CH3:29])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:17])[C:4]([NH:6][C@@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])=[O:5].[CH3:35][C:36]1[CH:37]=[C:38](Br)[CH:39]=[CH:40][C:41]=1[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(#N)C>CN(C)C=O>[CH3:34][C:2]([CH3:1])([CH3:33])[C@H:3]([NH:15][C:16]([C@H:18]([CH2:30]/[CH:31]=[CH:32]/[C:38]1[CH:39]=[CH:40][C:41]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[C:36]([CH3:35])[CH:37]=1)[C@H:19]([CH2:27][CH2:28][CH3:29])[C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])=[O:17])[C:4]([NH:6][C@@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])=[O:5]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 99648454-Bromo-2-methylbiphenylHCID 59875781tert-butyl (2S, 3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-(1-propyl)hex-5-enoate

Product 1

HCID 59875741tert-butyl (2S,3R,5E)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]-2-(1-propyl)hex-5-enoateYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

According to the method of Preparation 3, tert-butyl (2S, 3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-(1-propyl)hex-5-enoate (543 mg, 1.15 mmol) was reacted with 3-methyl-4-phenylbromobenzene (356 mg, 1.44 mmol) under palladium catalysis in a mixture of anhydrous acetonitrile and dimethylformamide (2:5, 7 mL) at 90° C. for 17 h. The mixture was concentrated under reduced pressure, poured into ethyl acetate (100 mL) and washed with water (2×100 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate) to give mainly tert-butyl (2S,3R,5E)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]-2-(1-propyl)hex-5-enoate as a colourless gum (460 mg, 63%). 1H nmr suggested that two alkene isomers, the (5Z) and (4E) were also present. The mixture of alkenes was taken onto the next step (see c, below).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionpoured into ethyl acetate (100 mL)
  3. washwashed with water (2×100 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate)

Sources & evidence

ORD record
ord-350010478e034048bcc6286ca651fae1
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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