Ammonium formate → 5-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane, (2S,3S,5S)-

HRID 976080Notes

Reaction equation

HRID 976080 reaction equation
C([N:8]([C@H:16]([C@@H:24]([OH:42])[CH2:25][C@@H:26]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)CC1C=CC=CC=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CCO.O.[Pd]>[NH2:8][C@H:16]([C@@H:24]([OH:42])[CH2:25][C@@H:26]([NH:34][C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 15383368(2S,3S,5S)-2-(N,N-Dibenzylamino)-3-hydroxy-5-(tert-butyloxycarbonylamino)-1,6-diphenylhexane

Product 1

HCID 119979265-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane, (2S,3S,5S)-

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of the product from Example 19C (150 gm, 250 mmol) dissolved in absolute EtOH (2 liters) was treated with 10% Pd/C (18 gm, prewetted), followed by addition of ammonium formate (78.6 gms, 1.25 moles) dissolved in H2O (200 ml). The resulting mixture was stirred at reflux for 2.5 hours. The mixture was cooled to room temperature and filtered through a pad of infusorial earth (20 g). The filter cake was washed 3 times with EtOH (70 ml each). The filtrate was concentrated/n vacuo. The residue was dissolved into EtOAc (1L) and washed (1N NaOH, followed by H2O, followed by brine), dried (Na2SO4), filtered and concentrated/n vacuo. to a constant weight of 95 gms. (99.2% of theory). The light yellow solid (91.5 gm of the 95 gm) was slurried in hot heptane (600 ml) (steam bath) and treated with isopropanol (45 ml), and swirled to effect solution. The solution was allowed to slowly cool to room temperature over 3 hours, kept at room temperature for 2 more hours and filtered. The filter cake was washed 10 times with 9/1 hexane-isopropanol (30 ml each) to give the desired product as an off-white finely crystalline solid which was dried to constant weight of 57.5 gm.

Workup

  1. temperatureat reflux for 2.5 hours
  2. filtrationfiltered through a pad of infusorial earth (20 g)
  3. washThe filter cake was washed 3 times with EtOH (70 ml each)
  4. concentrationThe filtrate was concentrated/n vacuo
  5. dissolutionThe residue was dissolved into EtOAc (1L)
  6. washwashed (1N NaOH, followed by H2O, followed by brine)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated/n vacuo
  10. additiontreated with isopropanol (45 ml)
  11. temperatureto slowly cool to room temperature over 3 hours
  12. customkept at room temperature for 2 more hours
  13. filtrationfiltered
  14. washThe filter cake was washed 10 times with 9/1 hexane-isopropanol (30 ml each)

Sources & evidence

ORD record
ord-483561eb972b4970b9a4fca8355cc7bf
Source dataset
uspto-grants-1997_03
Patent number
US05610193

Reaction notes

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