Methanol → 2,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl alpha-bromoacetate

HRID 847644Notes

Reaction equation

HRID 847644 reaction equation
[C:1]([NH:11][C@H:12]([C:16]([NH:18][CH:19]([CH:27]([OH:54])[CH:28]([NH:36][C:37](=[O:53])[C@H:38]([CH:50]([CH3:52])[CH3:51])[NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17])[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].N1C=CC=CC=1.[Br:61][CH2:62][C:63](Br)=[O:64].CO>C(Cl)Cl.C(Cl)(Cl)Cl>[Br:61][CH2:62][C:63]([O:54][CH:27]([CH:19]([NH:18][C:16](=[O:17])[C@H:12]([CH:13]([CH3:14])[CH3:15])[NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:28]([NH:36][C:37](=[O:53])[C@H:38]([CH:50]([CH3:52])[CH3:51])[NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:64]

Participants

7

Reactant 4

HCID 887MethanolHCID 1049PyridineHCID 61147Bromoacetyl bromideHCID 3011026benzyl N-[(1S)-1-[[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamoyl]-2-methyl-propyl]carbamate

Product 1

HCID 228455682,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl alpha-bromoacetateYield 55%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Procedure

The resultant compound of Example 70 (600 mg, 0.81 mmol) was dissolved in 8 mL of methylene chloride and 72 μL (0.9 mmol) of pyridine. The solution was cooled in an ice bath with stirring under a nitrogen atmosphere. α-Bromoacetyl bromide (181 mg, 0.9 mmol) was added in one portion and the ice bath was removed. The reaction mixture was stirred at ambient temperature for 3 h and then diluted with 150 mL of chloroform. The chloroform solution was washed with 150 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue (644 mg) was taken up in a mixture of chloroform and methanol and adsorbed onto approximately 1.5 g of 40 mesh silica gel in vacuo @40° C. The silica gel with the product adsorbed onto it was applied to a 1.0×40 cm column of 40 mesh silica gel and the column was eluted @~5 p.s.i. sequentially with 100 mL of chloroform and 100 mL of 1% methanol in chloroform to give 378 mg (55% yield) of the title compound; FAB MS M/Z: 859 (M+H)+. The 300 MHz 1NMR spectrum was consistent with the assigned structure.

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. customthe ice bath was removed
  3. stirringThe reaction mixture was stirred at ambient temperature for 3 h
  4. additiondiluted with 150 mL of chloroform
  5. washThe chloroform solution was washed with 150 mL of water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue (644 mg) was taken up in a mixture of chloroform and methanol
  10. customadsorbed onto approximately 1.5 g of 40 mesh silica gel in vacuo @40° C
  11. washthe column was eluted @~5 p.s.i

Sources & evidence

ORD record
ord-1e400b806df446b59204f60ba7fe928d
Source dataset
uspto-grants-1992_08
Patent number
US05142056

Reaction notes

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