Acetic Acid → tert-butyl (2R,5R)-5-[(benzylamino)methyl]-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

HRID 629712Notes

Reaction equation

HRID 629712 reaction equation
[CH:1]([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)=O.[CH2:46]([NH2:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.S([O-])([O-])(=O)=O.[Mg+2].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH2:46]([NH:53][CH2:1][C@H:3]1[N:8]([C:9]([O:11][C:12]([CH3:14])([CH3:15])[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:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:27][C:28]([O:30][CH3:31])=[O:29])[O:5][CH2:4]1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7504BenzylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 86726317tert-butyl (2R,5S)-5-formyl-2-[2-(2-{[N-(methoxycarbonyl)-b-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Product 1

HCID 86726319tert-butyl (2R,5R)-5-[(benzylamino)methyl]-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl (2R,5S)-5-formyl-2-[2-(2-{[N-(methoxycarbonyl)-b-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate (1 eq.) in MeOH (0.05 M) was added benzylamine (7 eq.), magnesium sulfate (1.2 eq.) and acetic acid (7 eq.). The solution was stirred for 30 minutes and sodium cyanoborohydride (2.3 eq.) was added and the reaction mixture was further stirred for 2 hours. The reaction mixture was then quenched by the addition of aqueous sodium bicarbonate and the aqueous layer was extracted with ethyl acetate three times. The combined organic layers were washed with water, dried over Na2SO4, filtered and concentrated. The residue was purified by automated silica gel flash chromatography system eluted with a gradient 30% to 100% of EtOAc/Hex to afford title compound.

Workup

  1. stirringthe reaction mixture was further stirred for 2 hours
  2. customThe reaction mixture was then quenched by the addition of aqueous sodium bicarbonate
  3. extractionthe aqueous layer was extracted with ethyl acetate three times
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by automated silica gel flash chromatography system
  9. washeluted with a gradient 30% to 100% of EtOAc/Hex

Sources & evidence

ORD record
ord-09f2390f87d84ebdbb6bea181ec4e315
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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