Benzaldehyde → HCID 86729879, compound

HRID 922528Notes

Reaction equation

HRID 922528 reaction equation
[ClH:1].[NH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:33])[C@@H:14]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[NH:15][C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])=[CH:8][CH:7]=1.C(=O)([O-])O.[Na+].[CH:39](=O)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.[BH4-].[Na+]>C1COCC1.CO>[ClH:1].[CH2:39]([NH:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:33])[C@@H:14]([CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[NH:15][C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])=[CH:8][CH:7]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 516892Sodium Bicarbonate2×HCID 4311764Sodium borohydrideHCID 86729881HCID 86729881, compound

Product 1

HCID 86729879HCID 86729879, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of N-[4-(trans-2-aminocyclopropyl)phenyl]-Nα-[(benzyloxy)carbonyl]-D-phenylalaninamide hydrochloride (100 mg) described in a document (J. Am. Chem. Soc. 2010, 132, 6827.), sodium hydrogen carbonate (27.0 mg), and methanol (4.00 mL) was added benzaldehyde (0.022 mL), and the mixture was stirred at 70° C. for 1 hr. The reaction mixture was diluted with dehydrated THF (6.00 mL), and cooled in an ice bath. Sodium borohydride (24.4 mg) was added and the mixture was stirred at 0° C. for 2 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted twice with ethyl is acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), and the fractions containing the object product were combined and concentrated. The residue was dissolved in methanol (5.00 mL), 10% hydrochloric acid methanol solution (1.00 mL) was added, and the mixture was concentrated under reduced pressure to give the title compound (84.6 mg).

Workup

  1. temperaturecooled in an ice bath
  2. stirringthe mixture was stirred at 0° C. for 2 hr
  3. concentrationthe mixture was concentrated under reduced pressure
  4. additionWater was added to the residue
  5. extractionthe mixture was extracted twice with ethyl
  6. washwashed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  10. additionthe fractions containing the object product
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in methanol (5.00 mL)
  13. addition10% hydrochloric acid methanol solution (1.00 mL) was added
  14. concentrationthe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-7a0c275080e64a5bbd96955aebe2c29a
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

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