Triacetoxyperiodinane → Telaprevir

HRID 391494Notes

Reaction equation

HRID 391494 reaction equation
[CH:1]1([C@H:7]([NH:41][C:42]([C:44]2[CH:49]=[N:48][CH:47]=[CH:46][N:45]=2)=[O:43])[C:8]([NH:10][C@@H:11]([C:37]([CH3:40])([CH3:39])[CH3:38])[C:12]([N:14]2[CH2:18][C@@H:17]3[CH2:19][CH2:20][CH2:21][C@@H:16]3[C@H:15]2[C:22]([NH:24][C@@H:25]([CH2:34][CH2:35][CH3:36])[CH:26]([OH:33])[C:27]([NH:29][CH:30]2[CH2:32][CH2:31]2)=[O:28])=[O:23])=[O:13])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.CC1(C)N([O])C(C)(C)CCC1.Cl[O-].[Na+].S(=O)(O)[O-].[Na+]>ClCCl>[CH:1]1([C@H:7]([NH:41][C:42]([C:44]2[CH:49]=[N:48][CH:47]=[CH:46][N:45]=2)=[O:43])[C:8]([NH:10][C@@H:11]([C:37]([CH3:38])([CH3:39])[CH3:40])[C:12]([N:14]2[CH2:18][C@@H:17]3[CH2:19][CH2:20][CH2:21][C@@H:16]3[C@H:15]2[C:22]([NH:24][C@@H:25]([CH2:34][CH2:35][CH3:36])[C:26](=[O:33])[C:27]([NH:29][CH:30]2[CH2:31][CH2:32]2)=[O:28])=[O:23])=[O:13])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 159087Triacetoxyperiodinane2×HCID 2724126TempoHCID 23634854Telaprevir, (alpha-ketoamide bond reduced)-2×HCID 23665760Sodium HypochloriteHCID 23665763Sodium Bisulfite

Product 1

HCID 3010818Telaprevir

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound is prepared by oxidation of the product of Step h with a suitable oxidizing reagent such as Dess-Martin periodinane or TEMPO and sodium hypochlorite. Specifically, in a flask containing 1.31 g of (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide in 40 mL of dichloromethane is added at room temperature 1.06 g of Dess-Martin periodinane. After 2 hours of stirring, 50 mL of sodium bisulfite (1N) is added, and the mixture is stirred for 30 minutes. The 2 phases are separated, the organic is washed with water twice, brine and dried over Na2SO4. The crude product was purified by chromatography on silica (ethyl acetate 20-100% in Hexanes) to give the title compound. The diastereoisome ratio is determined by chiral HPLC normal phase.

Workup

  1. stirringthe mixture is stirred for 30 minutes
  2. customThe 2 phases are separated
  3. washthe organic is washed with water twice
  4. dry with materialbrine and dried over Na2SO4
  5. customThe crude product was purified by chromatography on silica (ethyl acetate 20-100% in Hexanes)

Sources & evidence

ORD record
ord-db32157f4c124b77bce2000049c4d30d
Source dataset
uspto-grants-2013_02
Patent number
US08383858B2

Reaction notes

Loading…