Cornforth reagent → (3S,6R)-4-(tert-butoxycarbonyl)-6-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-3-carboxylic acid

HRID 629700Notes

Reaction equation

HRID 629700 reaction equation
[OH:1][CH2:2][C@H:3]1[N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][C@@H:6]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH:24][C:25](=[O:45])[C@H:26]([CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:27][C:28]([O:30][CH3:31])=[O:29])[O:5][CH2:4]1.C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-:58][Cr](O[Cr]([O-])(=O)=O)(=O)=O>CN(C=O)C>[C:12]([O:11][C:9]([N:8]1[CH2:7][C@@H:6]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH:24][C:25](=[O:45])[C@H:26]([CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:27][C:28]([O:30][CH3:31])=[O:29])[O:5][CH2:4][C@H:3]1[C:2]([OH:58])=[O:1])=[O:10])([CH3:14])([CH3:15])[CH3:13]

Participants

4

Reactant 2

HCID 2724130Cornforth reagentHCID 86726307(2R,5R)-5-hydroxymethyl-2-{2-[2-((S)-2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-phenyl]-ethyl}-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 86726308(3S,6R)-4-(tert-butoxycarbonyl)-6-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To tert-butyl (2R,5R)-5-(hydroxymethyl)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate (1 eq) in DMF (0.1M) at rt were added PDC (10 eq) and 4A molecular sieve (1 g/mmol of substrate). The reaction mixture was stirred at rt for 16 hrs. The reaction mixture was then filtered on a celite and the celite pad was washed with EtOAc and water. The filtrate was extracted with EtOAc. The combined organic layers were washed with brine, 1N aqueous HCl and brine, dried over Na2SO4, filtered and concentrated. The crude product was used as such for next step.

Workup

  1. filtrationThe reaction mixture was then filtered on a celite
  2. washthe celite pad was washed with EtOAc and water
  3. extractionThe filtrate was extracted with EtOAc
  4. washThe combined organic layers were washed with brine, 1N aqueous HCl and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-306cf645861a4f429b86a208025f74df
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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