Imidazole → HCID 70149816, compound

HRID 2394151Notes

Reaction equation

HRID 2394151 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])=[C:19]([CH3:25])[C:18]=1[CH3:26])[C:13]([OH:15])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CN=C1.C([Si](C)(C)Cl)(C)(C)C>CN(C=O)C>[C:1]([NH:8][C@H:9]([C@H:10]1[O:27][C:13](=[O:15])[C@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([CH3:25])[C:18]=2[CH3:26])[CH2:11]1)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 22876403HCID 22876403, compound

Product 1

HCID 70149816HCID 70149816, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1.153 g (2.445 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,3-dimethyl-4-methoxyphenyl)methyl]hexanoic acid, 1.372 g (20.05 mmol) of imidazole and 1.709 g (11.0 mmol) of tert-butyldimethylchlorosilane in 8.7 ml of abs. DMF is stirred at RT for 18 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 sodium sulfate and evaporated on a RE at approximately 30° C. The resulting product is dissolved in 28.8 ml of methanol and 11.2 ml of THF, and this solution is treated, at RT, with 1.962 g of potassium carbonate in 11.2 ml of water. After having been stirred for 2.25 h, the reaction mixture is concentrated down to half its volume at approximately 30° C. and the residue is treated with ethyl acetate and (cold) 10% citric acid solution, and the phases are separated. The organic phase is washed a further two times with saline. The combined aqueous phases are reextracted with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated. The residue is purified by being chromatographed twice on silica gel (hexane:ethyl acetate, 1:1 and then 3:1), and the title compound is obtained. TLC Rf (hexane:ethyl acetate. 1:1)=0.42. FAB-MS (M+H)+ =586. IR (KBr) inter alia: 1711, 1485, 1260 and 1107 cm-1. 1 H-NMR (CD3OD) inter alia: 7.30-7.06 (m, 5H); 6.91 and 6.65 (each d, each 1H); 6.00 and 5.41 (each d, in all 1H from NH); 3.75 (s, 3H); 2.21 and 2.12 (each s, each 3H); 1.31 and 1.21 (each s, in all 9H from Boc); 0.89 (s, 9H); 0.12 and 0.08 (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 sodium sulfate
  5. customevaporated on a RE at approximately 30° C
  6. dissolutionThe resulting product is dissolved in 28.8 ml of methanol
  7. addition11.2 ml of THF, and this solution is treated, at RT, with 1.962 g of potassium carbonate in 11.2 ml of water
  8. concentrationthe reaction mixture is concentrated down to half its volume at approximately 30° C.
  9. additionthe residue is treated with ethyl acetate and (cold) 10% citric acid solution
  10. customthe phases are separated
  11. washThe organic phase is washed a further two times with saline
  12. dry with materialThe combined organic phases are dried over sodium sulfate
  13. concentrationconcentrated
  14. customThe residue is purified
  15. customby being chromatographed twice on silica gel (hexane

Sources & evidence

ORD record
ord-53c228df091942ee92c72358599c2be4
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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