Imidazole → HCID 15454935, compound

HRID 2287507Notes

Reaction equation

HRID 2287507 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@H:15]([CH2:16][OH:17])[C@@H:14]([CH2:18][O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@H:13]([C:27]([O:29][CH3:30])=[O:28])[C@@H:12]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[Si:42](Cl)([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43]>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[C@H:15]([CH2:16][O:17][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[C@@H:14]([CH2:18][O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@H:13]([C:27]([O:29][CH3:30])=[O:28])[C@@H:12]1[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 15454934HCID 15454934, compound

Product 1

HCID 15454935HCID 15454935, compoundYield 117.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred and ice-cooled solution of crude (2R*,3S*,4S*,5S*)-1-benzyloxycarbonyl-4-benzyloxymethyl-5-hydroxymethyl-3-methoxycarbonyl-2-phenylpyrrolidine (15.9 g, ca.29.0 mmol) and imidazole (Im, 7.90 g, 116 mmol) in DMF (32.0 ml) was added t-butyldimethylsilyl chloride (8.74 g, 58.0 mmol)in one portion. The cooling bath was removed immediately after the addition, and the stirring was continued at room temperature for ca.5 hours. The reaction mixture was diluted with PhMe--AcOEt (2:1, 300 ml), washed with H2O (×3), and sat. NaCl aq. solution (×2), dried (MgSO4), and concentrated in vacuo to give a colorless oil (20.5 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 200 g). Elution with n-hexane-AcOEt (50:1→20:1→15:1) gave title compound (16.8 g, 96%) as a colorless viscous oil: IR νmax (film): 1743(s), 1705(vs), 1495(m), 1100(s), 780(s), 745(s), 737(s), 700(s) cm-1 ; 1H-NMR δ: 7.48-7.37(m, 3H), 7.37-7.14(m, 11H), 6.90(br.s, 1H), 5.27(br.d,J=6.1 Hz, 1H), 5.02(br.s, 2H), 4.51-4.41(m, 1H), 4.47(s, 2H), 3.97(dd, J=10.3, 2.6 Hz, 1H), 3.94-3.83(m, 1H), 3.60(d, J=3.7 Hz, 2H), 3.54(dd, J=11.8, 9.5 Hz, 1H), 3.33-3.15(m,1H), 3.28(s, 3H), 0.90(br.s, 9H), 0.05(br.s, 6H) ppm.

Workup

  1. customThe cooling bath was removed immediately
  2. additionafter the addition
  3. customwas continued at room temperature
  4. custom5 hours
  5. additionThe reaction mixture was diluted with PhMe--AcOEt (2:1, 300 ml)
  6. washwashed with H2O (×3), and sat. NaCl aq. solution (×2)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d45273deafe744b78a1cd960e0c9757c
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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