Oxalic acid dihydrate → HCID 70191891, compound

HRID 1738729Notes

Reaction equation

HRID 1738729 reaction equation
O.O.[C:3]([OH:8])(=[O:7])[C:4]([OH:6])=[O:5].[C:9]([O:13][C:14]([NH:16][C@H:17]([C@@H:25]([OH:36])[CH2:26][C@@H:27]([NH2:35])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(OC(N[C@H]([C@@H](O)C[C@H](N)CC1C=CC=CC=1)CC1C=CC=CC=1)=O)(C)(C)C>CO>[C:3]([OH:8])(=[O:7])[C:4]([OH:6])=[O:5].[C:9]([O:13][C:14]([NH:16][C@H:17]([C@@H:25]([OH:36])[CH2:26][C@@H:27]([NH2:35])[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 61373Oxalic acid dihydrateHCID 103178781,1-Dimethylethyl N-[(1S,2S,4S)-4-amino-2-hydroxy-5-phenyl-1-(phenylmethyl)pentyl]carbamateHCID 15428319(2S,3S,5R)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane

Product 1

HCID 70191891HCID 70191891, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(5S,1'S)-3-Phenylmethyl-5-(1'-tert-butoxycarbonylamino-2'-phenylethyl)-2-isoxazoline (2.0 g, 5.26 mmol) was dissolved in an ammonia/methanol solution (3%, 20 ml). A 3% Pt-on-carbon catalyst (100 mg, 5% by weight based on substrate) was added thereto. The mixture was stirred for 21 hours in a hydrogen atmosphere at atmospheric pressure. The catalyst was removed by filtration under reduced pressure, and then the filtrate was concentrated under reduced pressure. A foamy residue (2.0 g) containing (2S,3S,5S)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane and (2S,3S.5R)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane was obtained. By the HPLC analysis of the residue (absolute calibration curve method) using CHIRALPAK AD (trade name), 1.47 g of (2S,3S,5S)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane (yield: 73%) and 0.28 g of (2S,3S,5R)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane (reaction yield: 14%) were contained. Oxalic acid dihydrate (633 mg, 5.26 mmol) was added to the residue, the mixture was heated to dissolved in aqueous methanol (water content: 20% v/v, 22 ml). When the mixture was dissolved, it was cooled and crystals precipitated were collected by filtration. The crystals were washed with aqueous methanol (water content: 20%) and dried under reduced pressure to give colorless crystals. By HPLC analysis of the crystals, (2S,3S,5S)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane and (2S,3S,5R)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane were contained in the ratio of 97:3. Part of the crystals were further recrystallized with aqueous methanol (water content: 20%) to give the pure desired compound in crystals, which were confirmed, by HPLC, not to contain (2S,3S,5R)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane.

Workup

  1. temperaturethe mixture was heated
  2. dissolutionWhen the mixture was dissolved
  3. temperatureit was cooled
  4. customcrystals precipitated
  5. filtrationwere collected by filtration
  6. washThe crystals were washed with aqueous methanol (water content: 20%)
  7. customdried under reduced pressure
  8. customto give colorless crystals
  9. customPart of the crystals were further recrystallized with aqueous methanol (water content: 20%)

Sources & evidence

ORD record
ord-9306f24aee184c22b7f5b930b79c488a
Source dataset
uspto-grants-1999_10
Patent number
US05962692

Reaction notes

Loading…