Methyl 2-((s)-2-(benzyloxycarbonylamino)-3-methylbutanamido)-3-(7-bromo-1h-indol-3-yl)propanoate → methyl 2-((S)-1-(benzyloxycarbonylamino)-2-methylpropyl)-5-(7-bromo-1H-indol-3-yl)oxazole-4-carboxylate

HRID 494376Notes

Reaction equation

HRID 494376 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH:32]([CH3:34])[CH3:33])[C:13]([NH:15][CH:16]([CH2:21][C:22]1[C:30]2[C:25](=[C:26]([Br:31])[CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1)[C:17]([O:19][CH3:20])=[O:18])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCCC1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:13]1[O:14][C:21]([C:22]2[C:30]3[C:25](=[C:26]([Br:31])[CH:27]=[CH:28][CH:29]=3)[NH:24][CH:23]=2)=[C:16]([C:17]([O:19][CH3:20])=[O:18])[N:15]=1)[CH:32]([CH3:34])[CH3:33])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 59595036Methyl 2-((s)-2-(benzyloxycarbonylamino)-3-methylbutanamido)-3-(7-bromo-1h-indol-3-yl)propanoate

Product 1

HCID 59595035methyl 2-((S)-1-(benzyloxycarbonylamino)-2-methylpropyl)-5-(7-bromo-1H-indol-3-yl)oxazole-4-carboxylateYield 109.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dichlorodicyanoquinone (340.8 g, 1,500 mmol) was added to a stirred solution of the title compound of Example 4 (361.4 g, 681 mmol) dissolved in tetrahydrofuran (15 L) and heated to reflux for 6 hours at which time HPLC indicated complete reaction. The reaction was concentrated to ¼ its volume and diluted with ethyl acetate (12 L). The resulting black solution was washed three times with saturated aqueous NaHCO3 (5.5 L). The organic layer was dried over sodium sulfate and concentrated to give the title compound as a black solid (392 g, 100% yield). 1H NMR (CDCl3): consistent with proposed structure.

Workup

  1. temperatureheated
  2. temperatureto reflux for 6 hours at which time HPLC
  3. customreaction
  4. concentrationThe reaction was concentrated
  5. additiondiluted with ethyl acetate (12 L)
  6. washThe resulting black solution was washed three times with saturated aqueous NaHCO3 (5.5 L)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d7e376a64af04cc6b80140b12cb411d8
Source dataset
uspto-grants-2009_05
Patent number
US07538129B2

Reaction notes

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