Benzyl Alcohol → Benzyl Nalpha-(9-fluorenylmethoxycarbonyl)-Nepsilon-(t-butoxycarbonyl)-L-lysine

HRID 1397116Notes

Reaction equation

HRID 1397116 reaction equation
[NH:1]([C:18]([O:20][CH2:21][CH:22]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28]2[C:23]1=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:19])[C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[CH2:35](O)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:35]([N:1]([C:18]([O:20][CH2:21][CH:22]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=2[C:29]2[C:34]1=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:19])[C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 10868DicyclohexylcarbodiimideHCID 2724628Fmoc-Lys(Boc)-OH

Product 1

HCID 86666529Benzyl Nalpha-(9-fluorenylmethoxycarbonyl)-Nepsilon-(t-butoxycarbonyl)-L-lysineYield 96.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of Fmoc-Lys(Boc)-OH (47, 2.0 g, 4.27 mmol) and benzyl alcohol (531 μL, 5.12 mmol) in CH2Cl2 (8.5 mL) at 0° C. was added DMAP (52 mg, 0.43 mmol) and DCC (1.06 g, 5.12 mmol). The mixture was stirred for 2 h at 0° C. and 3 h at room temperature, then filtered. Solids were washed with small portions of CH2Cl2 and the combined filtrates were concentrated, redissolved in EtOAc, washed with H2O, 0.5 N aqueous HCl solution, saturated NaHCO3 solution, saturated NaCl solution, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on a Biotage™ flash chromatography system, using a gradient of 0-10% EtOAc in CH2Cl2 to furnish compound 48 (2.3 g, 96%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.25-1.39 (m, 2H), 1.40-1.52 (m, 2H), 1.43 (s, 9H), 1.66-1.75 (m, 1H), 1.82-1.90 (m, 1H), 3.02-3.11 (m, 2H), 4.20-4.24 (m, 1H), 4.35-4.52 (m, 4H), 5.16 (d, J=12.0 Hz, 1H), 5.22 (d, J=12.0 Hz, 1H), 5.39 (bd, J=8.0 Hz, 1H), 7.29-7.42 (m, 9H), 7.60 (d, J=7.5 Hz, 2H), 7.77 (d, J=7.5 Hz, 2H).

Workup

  1. filtrationfiltered
  2. washSolids were washed with small portions of CH2Cl2
  3. concentrationthe combined filtrates were concentrated
  4. dissolutionredissolved in EtOAc
  5. washwashed with H2O, 0.5 N aqueous HCl solution, saturated NaHCO3 solution, saturated NaCl solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography on a Biotage™ flash chromatography system

Sources & evidence

ORD record
ord-1ca09724d9844151a2b4c4bfe0b14628
Source dataset
uspto-grants-2014_12
Patent number
US08901072B2

Reaction notes

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