Methanol → HCID 178425324, compound

HRID 29768Notes

Reaction equation

HRID 29768 reaction equation
[Li+].[OH-].C([O:5][C:6](=[O:50])[CH:7]([C:31]([CH:35]([NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[CH:36]([CH3:38])[CH3:37])([OH:34])[PH2:32]=[O:33])[CH2:8][C:9]1[CH:10]=[N:11][C:12]([N:16](C(OC(C)(C)C)=O)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:13]([CH3:15])[CH:14]=1)C.CO>C(#N)C>[CH2:43]([O:42][C:40]([NH:39][CH:35]([C:31]([OH:34])([PH2:32]=[O:33])[CH:7]([CH2:8][C:9]1[CH:10]=[N:11][C:12]([NH:16][C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])=[C:13]([CH3:15])[CH:14]=1)[C:6]([OH:50])=[O:5])[CH:36]([CH3:38])[CH3:37])=[O:41])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 178471150HCID 178471150, compound

Product 1

HCID 178425324HCID 178425324, compoundYield 63.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1 M LiOH (2 mL) was added dropwise to a solution of 2-[(1-benzyloxycarbonylamino-2-methyl-propyl)-hydroxy-phosphinoylmethyl]-3-(6-bis(tert-butoxycarbonyl)amino-5-methyl-pyridin-3-yl)-propionic acid ethyl ester (100 mg, 0.145 mmol) in acetonitrile (2 mL). The mixture was stirred overnight and concentrated under reduced pressure. The mixture was purified by column chromatography (isopropanol/concentrated aqueous NH3/water, 4:2:1) to give impure product. The impure product was stirred with MeOH, filtered and concentrated under reduced pressure. The crude product was stirred with EtOH, filtered and concentrated under reduced pressure. The crude product was stirred with ethylacetate/ethanol, filtered and concentrated under reduced pressure to give 2-[(1-benzyloxycarbonylamino-2-methyl-propyl)-hydroxy-phosphinoylmethyl]-3-(6-tert-butoxycarbonylamino-5-methyl-pyridin-3-yl)-propionic acid (52 mg, 63.8%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe mixture was purified by column chromatography (isopropanol/concentrated aqueous NH3/water, 4:2:1)
  3. customto give impure product
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. stirringThe crude product was stirred with EtOH
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. stirringThe crude product was stirred with ethylacetate/ethanol
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5f5358ccea404184b38ae9bc8b6363cb
Source dataset
uspto-grants-2008_09
Patent number
US07423012B2

Reaction notes

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