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Sodium Chlorite → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pyrimidin-4-yl)piperidin-3-yl)acetic acid

HRID 1048333
Notes
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Reaction equation

HRID 1048333 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][CH:15]=3)[N:12]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][N:22]=3)[C:11](=[O:27])[C@:10]([CH2:29][CH:30]=[O:31])([CH3:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl([O-])=[O:33].[Na+].P([O-])(O)(O)=O.[Na+]>CC(O)(C)C.CC(=CC)C.C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][N:22]=3)[C:11](=[O:27])[C@:10]([CH2:29][C:30]([OH:33])=[O:31])([CH3:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 866607212-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pyrimidin-4-yl)piperidin-3-yl)acetaldehyde

Product 1

HCID 565912412-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pyrimidin-4-yl)piperidin-3-yl)acetic acid

Reagents, catalysts & solvents 4

HCID 962
Water
Solvent
HCID 6386tert-ButanolSolvent
HCID 8028TetrahydrofuranSolvent
HCID 105532-Methyl-2-buteneSolvent

Procedure

To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pyrimidin-4-yl)piperidin-3-yl)acetaldehyde (Example 110, Step C) (25 mg, 55 μmol) in a mixture of 2-methylpropan-2-ol (1.0 mL) and 2-methyl-2-butene (55 μL, 2.0 M soln in THF, 0.11 mmol) was added a solution of sodium chlorite (37 mg, 0.55 mmol) and sodium dihydrogen phosphate (4.8 mg, 50 μmol) in 550 μL of water at room temperature. The reaction mixture was stirred for 1 hour before it was quenched with water and extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by silica gel prep plate (10% MeOH/DCM) provided the title compound as a colorless solid.

Workup

  1. customwas quenched with water
  2. extractionextracted (2×EtOAc)
  3. washThe combined organic layers were washed with sat. aq. NaCl solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification of the residue by silica gel prep plate (10% MeOH/DCM)

Sources & evidence

ORD record
ord-e73403c0749143ffb907a7184cc113a2
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08569341B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes