HOAt → Tert-butyl 2-(aminocarbonyl)-4-fluorobenzylcarbamate

HRID 2252815Notes

Reaction equation

HRID 2252815 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:11]=1[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C[N:22](C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1>CN(C=O)C>[NH2:22][C:12]([C:11]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:10]=1[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:13]

Participants

5

Reactant 3

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110654742-[[(tert-Butoxycarbonyl)amino]methyl]-5-fluorobenzoic acid

Product 1

HCID 59645228Tert-butyl 2-(aminocarbonyl)-4-fluorobenzylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-{[(Tert-butoxycarbonyl)amino]methyl}-5-fluorobenzoic acid (800 mg, 2.97 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (854 mg, 4.46 mmol), and 1-hydroxy-7-azabenzotriazole (607 mg, 4.46 mmol) were added to dry DMF (10 mL) and stirred for 30 minutes to preform the activated ester. Ammonia gas was bubbled through the solution for 30 seconds and the reaction was allowed to stir for 5 minutes. The solvent was removed in vacuo and the residue was purified by flash column chromatography (ISCO column, 120 g silica) running a gradient of 0-40% acetone/hexane over 35 min. The product fractions were concentrated to afford the title compound as a white solid.

Workup

  1. customAmmonia gas was bubbled through the solution for 30 seconds
  2. stirringto stir for 5 minutes
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by flash column chromatography (ISCO column, 120 g silica)
  5. customover 35 min
  6. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-90de591c052c438e96e669424661f1cd
Source dataset
uspto-grants-2008_01
Patent number
US07323460B2

Reaction notes

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