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Allyl bromide → (3S,5R,6S)-3-allyl-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one

HRID 1048581
Notes
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Reaction equation

HRID 1048581 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Si:11]([O:28][CH2:29][C@@H:30]([N:33]1[C@H:38]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=2)[C@@H:37]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=2)[CH2:36][CH2:35][C:34]1=[O:53])[CH2:31][CH3:32])([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Br[CH2:55][CH:56]=[CH2:57].[Li+].CC([N-]C(C)C)C.Cl[CH2:67][O:68][CH2:69][CH2:70][Si:71]([CH3:74])([CH3:73])[CH3:72]>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O>[CH2:55]([C@@:35]1([CH2:67][O:68][CH2:69][CH2:70][Si:71]([CH3:74])([CH3:73])[CH3:72])[CH2:36][C@H:37]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=2)[C@@H:38]([C:39]2[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=2)[N:33]([C@@H:30]([CH2:31][CH3:32])[CH2:29][O:28][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:34]1=[O:53])[CH:56]=[CH2:57]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 7841Allyl bromideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 2724682Lithium diisopropylamideHCID 2733832Lithium hexamethyldisilazaneHCID 67999011(5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one

Product 1

HCID 68000283
(3S,5R,6S)-3-allyl-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Lithium bis(trimethylsilyl)amide, (1M solution in toluene, 4.76 mL, 4.76 mmol) was added to a solution of (5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 185, Step C, 2.0 g, 3.17 mmol) and 3-bromopropene (0.274 mL, 3.17 mmol) in THF at −78° C. The reaction was warmed to 0° C. and stirred for 2 hours. After recooling to −78° C., a solution of LDA (7.93 mmol in THF) followed by 2-(chloromethoxy)ethyltrimethylsilane (0.842 mL, 4.76 mmol) was added. The reaction was warmed to 50° C. and stirred for 1.5 hours. The reaction mixture was diluted with EtOAc and washed with HCl (1N). The organic extract was washed with satd NaCl and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by chromatography on silica gel, eluting with a gradient of 0% to 20% EtOAc in hexane, to provide (3S,5R,6S)-3-allyl-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one as the first eluting diastereomer and the title compound as the second diastereomer as an oil.

Workup

  1. customAfter recooling to −78° C.
  2. additionwas added
  3. temperatureThe reaction was warmed to 50° C.
  4. stirringstirred for 1.5 hours
  5. washwashed with HCl (1N)
  6. extractionThe organic extract
  7. washwas washed with satd NaCl
  8. dry with materialdried over Na2SO4
  9. filtrationThe solution was filtered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by chromatography on silica gel
  12. washeluting with a gradient of 0% to 20% EtOAc in hexane

Sources & evidence

ORD record
ord-8b527e8101ff4c79a4b4b97e5c6d8205
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08569341B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes