Imidazole → 5(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-phenyl-2(R)-[(2,4-dimethoxylphenyl)methyl]hexanoic acid

HRID 2394144Notes

Reaction equation

HRID 2394144 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@@H:10]([OH:27])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[O:25][CH3:26])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CN=C1.[C:40]([Si:44]([CH3:47])([CH3:46])Cl)([CH3:43])([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+]>CO.C1COCC1.O.CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@@H:10]([O:27][Si:44]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:47])[CH3:46])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[O:25][CH3:26])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 228764045(S)-(Boc-Amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-dimethoxyphenyl)methyl]hexanoic acid

Product 1

HCID 228764185(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-phenyl-2(R)-[(2,4-dimethoxylphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.5 g (3.17 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-dimethoxyphenyl)methyl]hexanoic acid, 1.76 g (25.36 mmol) of imidazole and 2.22 g (14.26 mmol) of tert-butyldimethylchlorosilane in 16 ml of abs. DMF is stirred at RT for 20 h under argon. After that, the reaction mixture is poured onto ice-water and the whole is extracted with ethyl acetate. The organic phase is washed with cold 10% citric acid solution and saline. The combined aqueous phases are reextracted with ethyl acetate. The combined organic phases are dried over Na2SO4, and the solvent is removed on a RE at about 30° C. An oil is obtained which is dissolved in 42.1 ml of methanol and 14.4 ml of THF, and this solution is then treated, at RT, with 2.5 g of potassium carbonate in 14.4 ml of water. After it has been stirred at RT for 2 h, the reaction mixture is concentrated down to half its volume at approximately 30° C. and the residue is diluted with ethyl acetate; the whole is then washed with 10% citric acid solution and with saline (both being cold). The combined aqueous phases are reextracted with ethyl acetate. The combined organic phases are dried over Na2 SO4 and evaporated. Chromatography on silica gel (D) affords the pure title compound. TLC Rf (C)=0.34.-FAB-MS (M+H)+ =588.-HPLC tRet =20.24 min (gradient II).-IR(KBr)=inter alia 1712, 1654, 1614, 1588 und 1507 cm-1.-1H-NMR(CD3OD)=inter alia 7.30-7.10/m (5H); 6.98/d (1H); 6.50/d (1H); 6.40/d×d (1H); 3.80 and 3.76/each s (each 3H); 1.31/s (9H); 0.93/s (9H); 0.14 and 0.11/each s (each 3H).

Workup

  1. additionAfter that, the reaction mixture is poured onto ice-water
  2. extractionthe whole is extracted with ethyl acetate
  3. washThe organic phase is washed with cold 10% citric acid solution and saline
  4. dry with materialThe combined organic phases are dried over Na2SO4
  5. customthe solvent is removed on a RE at about 30° C
  6. customAn oil is obtained which
  7. concentrationthe reaction mixture is concentrated down to half its volume at approximately 30° C.
  8. additionthe residue is diluted with ethyl acetate
  9. washthe whole is then washed with 10% citric acid solution and with saline (both being cold)
  10. customThe combined organic phases are dried over Na2 SO4
  11. customevaporated

Sources & evidence

ORD record
ord-0fdad2cce3dc4dadb81b67eb5c97cc00
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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