Sodium hydride → 4(2,2-Dimethoxyethyloxy)-benzoyl-(2S)-2-benzyloxycarbonylamino-beta-alanine tert-butyl ester

HRID 612855Notes

Reaction equation

HRID 612855 reaction equation
[C:1]([O:5][C:6](=[O:30])[C@@H:7]([NH:19][C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[CH2:8][NH:9][C:10](=[O:18])[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[H][H].[CH3:35][O:36][CH:37]([O:40][CH3:41])[CH2:38]Br>CN(C=O)C>[C:1]([O:5][C:6](=[O:30])[C@@H:7]([NH:19][C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[CH2:8][NH:9][C:10](=[O:18])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:38][CH:37]([O:40][CH3:41])[O:36][CH3:35])=[CH:13][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 24758Sodium hydride4×HCID 816722-Bromo-1,1-dimethoxyethaneHCID 153806404-Hydroxybenzoyl-(2S)-2-benzyloxycarbonylamino-beta-alanine tert-butyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 153806414(2,2-Dimethoxyethyloxy)-benzoyl-(2S)-2-benzyloxycarbonylamino-beta-alanine tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

1.8 g (4.34 mmol) of (1.2) were added to a suspension of 176 mg of a 55% strength sodium hydride suspension in oil (4.07 mmol of sodium hydride) in 10 ml of abs. DMF and the mixture was stirred until the evolution of hydrogen was complete (about 30 min). 620 mg (3.7 mmol) of bromoacetaldehyde dimethyl acetal were then added and the mixture was heated at 50° C. for 8 h and at 70° C. for 2 h. After fresh addition of 18 mg of the sodium hydride suspension in oil (0.41 mmol of sodium hydride), the mixture was heated at 70° C. for a further 4 h. After standing overnight, the reaction mixture was concentrated in a rotary evaporator and the residue was partitioned between H2O and CH2Cl2. The organic phase was separated off and dried over MgSO4, and the solvent was removed in vacuo. The residue was chromatographed on silica gel by means of MPLC using heptane/ethyl acetate. (1.3) was obtained as a colorless solid; melting point 115° C.

Workup

  1. custom(about 30 min)
  2. temperaturethe mixture was heated at 70° C. for a further 4 h
  3. concentrationthe reaction mixture was concentrated in a rotary evaporator
  4. customthe residue was partitioned between H2O and CH2Cl2
  5. customThe organic phase was separated off
  6. dry with materialdried over MgSO4
  7. customthe solvent was removed in vacuo
  8. customThe residue was chromatographed on silica gel by means of MPLC

Sources & evidence

ORD record
ord-071cac1230554ce996031b5c380420c8
Source dataset
uspto-grants-1999_12
Patent number
US06005117

Reaction notes

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