Acetic Acid → 3-(Tert-butyldimethylsilyloxy)-4-chlorobenzoic acid

HRID 375748Notes

Reaction equation

HRID 375748 reaction equation
BrC[C:3]1[C:18]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])=[C:17]([Cl:27])[CH:16]=[CH:15][C:4]=1[C:5]([O:7][Si](C(C)(C)C)(C)C)=[O:6].COC(=O)[C@H](CS)NC(=O)[C@H](CO)NC(OC(C)(C)C)=O.N12CCCN=C1CCCCC2.C(O)(=O)C>C(Cl)Cl>[Si:20]([O:19][C:18]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:27])[C:5]([OH:7])=[O:6])([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11727022N-[N-(t-butoxycarbonyl)-L-seryl]-L-cysteine methyl esterHCID 18991978Tert-butyldimethylsilyl 2-bromomethyl-3-(tert-butyldimethylsilyloxy)-4-chlorobenzoate

Product 1

HCID 690083053-(Tert-butyldimethylsilyloxy)-4-chlorobenzoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 5.1 g of tert-butyldimethylsilyl 2-bromomethyl-3-(tert-butyldimethylsilyloxy)-4-chlorobenzoate and 3.52 g of N-[N-(tert-butoxycarbonyl)-L-seryl]-L-cysteine methyl ester in 55 ml of methylene chloride was added within 30 minutes, at 0° C., a solution of 1.59 g of 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) in 15 ml of methylene chloride. Stirring was continued for 3 hours at 0° C., and subsequently the mixture was diluted with methylene chloride and stirred together with 100 ml of 1N aqueous acetic acid. The organic phase was washed with 10% sodium chloride solution, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was chromatographed on MCI-Gel CHP20P using as eluent a mixture of acetonitrile-water containing 40-0% water. The product was eluted with pure acetonitrile. Evaporation of the solvent afforded 2.7 g of 2-[[[(R)-2-[(S)-1-tert-butoxyformamido )-3-hydroxypropionylamino]-2-methoxycarbonyl-ethyl ]thio]methyl]-3 -(tert-butyldimethylsilyloxy)-4-chlorobenzoic acid as a white foam.

Workup

  1. washThe organic phase was washed with 10% sodium chloride solution
  2. dry with materialdried over sodium sulfate
  3. customthe solvent was evaporated in vacuo
  4. customThe residue was chromatographed on MCI-Gel CHP20P
  5. additiona mixture of acetonitrile-water containing 40-0% water
  6. washThe product was eluted with pure acetonitrile
  7. customEvaporation of the solvent

Sources & evidence

ORD record
ord-3310a76639644b75ad54e263c8d701ec
Source dataset
uspto-grants-1996_01
Patent number
US05486466

Reaction notes

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