Acetic Acid → HCID 54227914, compound

HRID 1108358Notes

Reaction equation

HRID 1108358 reaction equation
CO[C:3](=O)[C@H:4]([CH2:13][CH2:14][CH2:15][CH3:16])[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].Cl.[CH3:19][O:20][C:21](=[O:32])[C@H:22]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[NH2:23].C(O)(=O)C.C([BH3-])#N.[Na+]>C1(C)C=CC=CC=1.CO.O1CCCC1.O>[CH3:19][O:20][C:21](=[O:32])[C@H:22]([CH2:24][C:25]1[CH:26]=[CH:27][C:28]([OH:31])=[CH:29][CH:30]=1)[NH:23][CH2:3][C@@H:4]([NH:5][C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7])[CH2:13][CH2:14][CH2:15][CH3:16]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 76956Methyl tyrosinate hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 54278289HCID 54278289, compound

Product 1

HCID 54227914HCID 54227914, compoundYield 32.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under an argon gas stream, N-(tert-butoxycarbonyl)-L-norleucine methyl ester (10.7 g, 38 mmol) was dissolved in toluene (68 ml), and cooled to -78° C. To the solution, while keeping the temperature at -60 to -70° C., was added gradually aluminum diisobutyl hydride (toluene 1.0 M solution, 51 ml). After stirring at -78° C. for an hour, the cooling bath was removed, methanol (2 ml) was added to the mixture. Tyrosine methyl ester hydrochloride (13.6 g, 59 mmol) and acetic acid (3.5 g, 59 mmol) were dissolved in methanol (69 ml)-tetrahydrofuran (98 ml), and added to the mixture. After addition of a suspension of sodium cyanoborohydride (2.7 g, 43 mmol) in tetrahydrofuran (30 ml), the mixture was stirred at room temperature for 2.5 hours, and water was added thereto. The solid was removed by decantation, and the solution was concentrated under reduced pressure. The organic matters were extracted with ethyl acetate, and washed with a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution, successively. The organic layer was concentrated under reduced pressure and purified by column chromatography to give N-[(S)-2-(tert-butoxycarbonylamino)hexyl]-L-tyrosine methyl ester (4.9 g).

Workup

  1. customat -60 to -70° C.
  2. customthe cooling bath was removed
  3. additionmethanol (2 ml) was added to the mixture
  4. additionadded to the mixture
  5. stirringthe mixture was stirred at room temperature for 2.5 hours
  6. customThe solid was removed by decantation
  7. concentrationthe solution was concentrated under reduced pressure
  8. extractionThe organic matters were extracted with ethyl acetate
  9. washwashed with a saturated aqueous sodium bicarbonate solution, water
  10. concentrationThe organic layer was concentrated under reduced pressure
  11. custompurified by column chromatography

Sources & evidence

ORD record
ord-4772fb69aab64d3c9c312e7ea35fb368
Source dataset
uspto-grants-2000_05
Patent number
US06066672

Reaction notes

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