Acetic Acid → HCID 21187415, compound

HRID 1383733Notes

Reaction equation

HRID 1383733 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH:13]([NH:26][C:27](=[O:40])[CH:28]([NH:32]C(OC(C)(C)C)=O)[CH:29]([CH3:31])[CH3:30])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:16]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:41]([OH:44])(=O)[CH3:42].[C:45]([BH3-])#[N:46].[Na+].[OH2:49]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH:13]([NH:26][C:27](=[O:40])[CH:28]([NH:32][CH2:12][CH:13]([NH:46][C:45]([O:44][CH2:41][C:42]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1)=[O:49])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:29]([CH3:31])[CH3:30])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([C:22]([CH3:23])([CH3:25])[CH3:24])[CH:16]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 21187416HCID 21187416, compound

Product 1

HCID 21187415HCID 21187415, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 436 mg (0.786 mmol) of N-[2-(benzoxycarbonylamino)-1-[(3-tert-butyl-4-hydroxyphenyl)methyl]ethyl]-2-(tert-butoxycarbonylamino)-3-methyl butanamide in methylene chloride (2 ml), TFA (2 ml) was added and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and to the residue, saturated aqueous NaHCO3 was added under cooling with ice and the mixture was extracted with chloroform and washed with saturated brine. The organic layer was dried with magnesium sulfate and the solvent was distilled off under reduced pressure; the resulting residue was dissolved in MeCN (3 ml) and under cooling with ice, 245 mg (0.866 mmol) of Z-phenylalaninal, 0.1 ml of acetic acid and 98.8 mg (1.57 mmol) of sodium cyanoborohydride were added to the solution, which was then stirred for 3 hours. After adding water, the solution was extracted with chloroform and washed with saturated brine. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluting solvent; ethyl acetate:n-hexane=1:1) to give N-[2-benzoxycarbonylamino-1-[(3-tert-butyl-4-hydroxyphenyl)methyl]ethyl]-2-[[2-(benzoxycarbonylamino)-3-phenylpropyl]-amino]-3-methyl butanamide in the amount of 282 mg (50%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure and to the residue, saturated aqueous NaHCO3
  2. additionwas added
  3. temperatureunder cooling with ice
  4. extractionthe mixture was extracted with chloroform
  5. washwashed with saturated brine
  6. dry with materialThe organic layer was dried with magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. dissolutionthe resulting residue was dissolved in MeCN (3 ml)
  9. additionwere added to the solution, which
  10. stirringwas then stirred for 3 hours
  11. extractionthe solution was extracted with chloroform
  12. washwashed with saturated brine
  13. dry with materialThe organic layer was dried with magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. washthe resulting residue was subjected to silica gel column chromatography (eluting solvent; ethyl acetate:n-hexane=1:1)

Sources & evidence

ORD record
ord-e38c5d3552554adbbfd4b91d8a4fa735
Source dataset
uspto-grants-2001_07
Patent number
US06255285B1

Reaction notes

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