Imidazole → (3R,5R,6S)-3-allyl-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one

HRID 1048377Notes

Reaction equation

HRID 1048377 reaction equation
[CH2:1]([C@@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH2:25][OH:26])[C:5]1=[O:29])[CH:2]=[CH2:3].N1C=CN=C1.[C:35]([Si:39](Cl)([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([CH3:38])([CH3:37])[CH3:36]>CN(C=O)C>[CH2:1]([C@@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH2:25][O:26][Si:39]([C:35]([CH3:38])([CH3:37])[CH3:36])([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:5]1=[O:29])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 58574001(3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one

Product 1

HCID 68000518(3R,5R,6S)-3-allyl-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 615 mg (1.422 mmol) (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one (Example 126, Step B) in DMF (4741 μL) at 0° C. was added 1H-imidazole (97 mg, 1.422 mmol) followed by tert-butylchlorodiphenylsilane (473 μL, 1.849 mmol). The mixture was stirred at 0° C. for 15 min and then warmed to room temperature. The mixture was stirred at room temperature for 30 min and then quenched with sat. NH4Cl. The mixture was extracted with EtOAc and the organic layer was washed with water, 1 M LiCl, and sat. aq. NaCl solution. The mixture was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (24 g column; eluent: 0 to 30% EtOAc in hexanes) to give the title compound.

Workup

  1. temperaturewarmed to room temperature
  2. stirringThe mixture was stirred at room temperature for 30 min
  3. customquenched with sat. NH4Cl
  4. extractionThe mixture was extracted with EtOAc
  5. washthe organic layer was washed with water, 1 M LiCl, and sat. aq. NaCl solution
  6. dry with materialThe mixture was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (24 g column; eluent: 0 to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-021e72988fea4f5f8fc01984a4f05adb
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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