Triacetoxyperiodinane → Morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-formyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide

HRID 1455604Notes

Reaction equation

HRID 1455604 reaction equation
[F:1][C:2]([F:31])([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:3][C@H:4]([NH:15][C:16]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:17])[C:5](=[O:14])[NH:6][C@@:7]([CH2:12][OH:13])([CH3:11])[CH2:8][CH2:9][CH3:10].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:31][C:2]([F:1])([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:3][C@H:4]([NH:15][C:16]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:17])[C:5](=[O:14])[NH:6][C@@:7]([CH:12]=[O:13])([CH3:11])[CH2:8][CH2:9][CH3:10]

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 86607350morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide

Product 1

HCID 11305219Morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-formyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amideYield 38.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of Morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide (217 mg) and Dess-Martin Periodinane (15% in DCM, 2 eq.) in DCM (5 mL) is stirred at room temperature for 3 hrs and quenched with a solution of sodium thiosulfate in saturated NaHCO3. The product is extracted with ethyl acetate and washed with saturated NaCl solution. Organic phase is dried over anhydrous MgSO4, solvent evaporated under reduced pressure. Purification by silica gel chromatography eluting with ethyl acetate-heptane mixture gives Morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-formyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide (83 mg, 38%).

Workup

  1. customquenched with a solution of sodium thiosulfate in saturated NaHCO3
  2. extractionThe product is extracted with ethyl acetate
  3. washwashed with saturated NaCl solution
  4. dry with materialOrganic phase is dried over anhydrous MgSO4, solvent
  5. customevaporated under reduced pressure
  6. customPurification by silica gel chromatography
  7. washeluting with ethyl acetate-heptane mixture

Sources & evidence

ORD record
ord-46c575c4720e4c11907de4bcbb5e0a1d
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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