Benzylamine → Nalpha-[4(S)-tert-Butoxycarbonylamino-3(S)-hydroxy-6-methylheptyl]-L-leucine benzylamide

HRID 64644Notes

Reaction equation

HRID 64644 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:23][CH:24]([CH3:26])[CH3:25])[C@@H:10]([OH:22])[CH2:11][CH2:12][NH:13][C@H:14]([C:19]([OH:21])=O)[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([O-])(O)=O.[Na+].[N-]=[N+]=[N-].[Na+].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>CN(C=O)C>[CH2:27]([NH:34][C:19](=[O:21])[C@H:14]([CH2:15][CH:16]([CH3:17])[CH3:18])[NH:13][CH2:12][CH2:11][C@H:10]([OH:22])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:23][CH:24]([CH3:26])[CH3:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 7504BenzylamineHCID 33557Sodium AzideHCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 13672673Nalpha-[4(S)-tert-Butoxycarbonylamino-3(S)-hydroxy-6-methylheptyl]-L-leucine

Product 1

HCID 18604257Nalpha-[4(S)-tert-Butoxycarbonylamino-3(S)-hydroxy-6-methylheptyl]-L-leucine benzylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-30 °C

Procedure

3 (540 mg) was suspended in DMF (23 ml) and treated with benzylamine (0.374 ml), TEA (0.401 ml), NaHCO3 (solid) (924 mg) and sodium azide (117 mg). The suspension was cooled to -30° C., treated with DPPA (0.934 ml), and stirred at 0° C. for 72 hours. After removal of the DMF in vacuo, the residue was treated with 10% citric acid and extracted with EtOAc (3x). The combined extracts were washed with 10% citric acid (1x), H2O (1x), 10% NaHCO3 (aqueous) (1x), and brine (1x), dried over MgSO4, filtered and evaporated to dryness in vacuo to give a crude colorless oil (1.5 g). Flash chromatography on silica gel (90/10/1/1 of CH2Cl2 /MeOH/H2O/HOAc) gave 7 as a sticky foam (440 mg).

Workup

  1. customAfter removal of the DMF in vacuo
  2. additionthe residue was treated with 10% citric acid
  3. extractionextracted with EtOAc (3x)
  4. washThe combined extracts were washed with 10% citric acid (1x), H2O (1x), 10% NaHCO3 (aqueous) (1x), and brine (1x)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness in vacuo
  8. customto give a crude colorless oil (1.5 g)

Sources & evidence

ORD record
ord-b657b476726f4db8943f449aeab25c95
Source dataset
uspto-grants-1986_09
Patent number
US04609641

Reaction notes

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