Imidazole → (5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)piperidin-2-one

HRID 932050Notes

Reaction equation

HRID 932050 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22][OH:23])[C:11](=[O:26])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.N1C=CN=C1.[Si:32](Cl)([C:45]([CH3:48])([CH3:47])[CH3:46])([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C=O)C>[Si:32]([O:23][CH2:22][C@@H:21]([N:12]1[C@H:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=2)[C@@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH2:9][CH2:10][C:11]1=[O:26])[CH2:24][CH3:25])([C:45]([CH3:48])([CH3:47])[CH3:46])([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 58573722(5R,6S)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one

Product 1

HCID 67998307(5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2.03 g (5.2 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one (Example 121, Step H) and 877 mg (12.9 mmol) of imidazole in DMF (32 mL) was added 1.9 mL (7.3 mmol) of tert-butyldiphenylsilyl chloride. The resulting light yellow solution was stirred at room temperature for 4.5 h. The reaction was partitioned between water and EtOAc (2×), and then the combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (0 to 4% MeOH/DCM, gradient elution) provided the title compound as a white solid.

Workup

  1. customThe reaction was partitioned between water and EtOAc (2×)
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customPurification of the residue by flash chromatography on silica gel (0 to 4% MeOH/DCM, gradient elution)

Sources & evidence

ORD record
ord-81f2ea91839040348d6a4c5b26fa797a
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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