Benzaldehyde → NepsilonBenzyl-Nalpha-BOC-L-Lysine tert-Butyl Ester

HRID 1741434Notes

Reaction equation

HRID 1741434 reaction equation
Cl.[C:2]([O:6][C:7](=[O:22])[C@H:8]([CH2:17][CH2:18][CH2:19][CH2:20][NH2:21])[NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:5])([CH3:4])[CH3:3].[CH:23](=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCO.C([BH3-])#N.[Na+]>C(Cl)(Cl)Cl>[C:2]([O:6][C:7](=[O:22])[C@H:8]([CH2:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[NH:9][C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 702EthanolHCID 5003444Sodium cyanoborohydrideHCID 513584377750-45-0

Product 1

HCID 10786720NepsilonBenzyl-Nalpha-BOC-L-Lysine tert-Butyl EsterYield 54%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Nα -BOC-L-lysine t-butyl ester hydrochloride salt (3) (25.97 g, 76.64 mmol) was dissolved in CHCl3 (300 ml) and washed with saturated aqueous Na2CO3 solution (2×100 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated. The resultant oil (the free amine) was combined with benzaldehyde (10.42 g, 98.13 mmol), EtOH (150 ml) and activated 3 Å molecular sieves (46.0 g). The mixture was stirred under N2 for 6 hours. Sodium cyanoborohydride (2.41 g, 38.4 mmol) was added and the mixture was stirred overnight at room temperature. The brown mixture was filtered and the filtrate acidified to pH 2 with 1 N HCl (110 ml). The yellow solution was concentrated to dryness, dissolved in CHCl3, washed with saturated Na2CO3 solution and water. The organic layer was separated, dried (MgSO4) and concentrated. Flash column chromatography (10% EtOH/CHCl3, Rf =0.30) afforded the Nε -benzyl-Nα -BOC-L-lysine t-butyl ester (4) (16.16 g, 54%) as a colorless oil. 1H NMR (CD3OD) δ7.34-7.20 (m, 5H), 3.91 (dd, 1H, J=9.0, 5.1 Hz), 3.72 (s, 2H), 2.58 (t, 2H, J=7.2 Hz), 1.82-1.30 (m, 6H), 1.45 (s, 9H), 1.43 (s, 9H); 13C NMR (CDCl3) δ171.9, 155.3, 140.1, 128.3, 128.1, 126.9, 81.6, 79.5, 53.9, 48.9, 32.7, 29.5, 28.3, 27.9, 22.9. HRMS m/z calcd. for C22H36N2O4 392.2675, found 392.2676. Anal. calcd. for C22H35N2O4 : C 67.32, H 9.24, N 7.14. Found: C 67.40, H 9.28, N 7.16. [α]25D +6.9° (c=1.00, CDCl3).

Workup

  1. washwashed with saturated aqueous Na2CO3 solution (2×100 ml)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringthe mixture was stirred overnight at room temperature
  7. filtrationThe brown mixture was filtered
  8. concentrationThe yellow solution was concentrated to dryness
  9. dissolutiondissolved in CHCl3
  10. washwashed with saturated Na2CO3 solution and water
  11. customThe organic layer was separated
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-838c884227ff47f5894a7ecd1f5a3cf7
Source dataset
uspto-grants-1999_10
Patent number
US05973113

Reaction notes

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