4-Nitrophenol → N-BOC-glvcylproline-4-nitrophenvl ester

HRID 1532946Notes

Reaction equation

HRID 1532946 reaction equation
[C:1]([NH:8][CH2:9][C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=[O:15])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[N+:20]([C:23]1[CH:28]=[CH:27][C:26](O)=[CH:25][CH:24]=1)([O-:22])=[O:21].C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[N+:20]([C:23]1[CH:28]=[CH:27][C:26]([O:15][C:14](=[O:16])[C@@H:13]2[CH2:17][CH2:18][CH2:19][N:12]2[C:10](=[O:11])[CH2:9][NH:8][C:1]([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2])=[CH:25][CH:24]=1)([O-:22])=[O:21]

Participants

5

Reactant 3

HCID 9804-NitrophenolHCID 10868DicyclohexylcarbodiimideHCID 11673468Boc-gly-pro-OH

Product 1

HCID 15384682N-BOC-glvcylproline-4-nitrophenvl esterYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3.0 g (11.6 mmol) of N-BOC-glycylproline and 1.93 g (13.9 mmol) of 4-nitrophenol in 82 mL of dry THF was cooled to 0° C. and 3.34 g (16.2 mmol) of DCC was added. The mixture was stirred at 0° C. for 1 hour, the ice bath was removed, and the mixture was stirred for 16 hours at room temperature. HOAc (579 μL) was added to the mixture and it was allowed to stir for 30 minutes. The mixture was kept in the freezer for 30 minutes and filtered under vacuum. The filtrate was concentrated and purified by silica gel chromatography (18×150 mm bed, 2.5% EtOAc/97.5% CH2Cl2/1% HOAc). Traces of acetic acid were removed by concentrating from dioxane several times on the rotary evaporator. The concentrate was triturated with 3/1 hexane Et2O and the resulting white solid was collected by filtration to give 4.1 g (90%) of compound 15 as a white solid; TLC Rf 0.09, 40/60/1 EtOAc/hexane/HOAc; 1H NMR(CDCl3) δ 1.09-2.55 (m, 4H), 1.48 (s, 9H), 3.47-3.77 (m, 2H), 4.05 (m, 2H), 4.74 (m, 1H), 5.45 (bd s, 1H), 7.35 (d, 2H), 8.30 (d, 2H).

Workup

  1. customthe ice bath was removed
  2. stirringthe mixture was stirred for 16 hours at room temperature
  3. additionHOAc (579 μL) was added to the mixture and it
  4. stirringto stir for 30 minutes
  5. waitThe mixture was kept in the freezer for 30 minutes
  6. filtrationfiltered under vacuum
  7. concentrationThe filtrate was concentrated
  8. custompurified by silica gel chromatography (18×150 mm bed, 2.5% EtOAc/97.5% CH2Cl2/1% HOAc)
  9. customTraces of acetic acid were removed
  10. concentrationby concentrating from dioxane several times on the rotary evaporator
  11. customThe concentrate was triturated with 3/1 hexane Et2O
  12. filtrationthe resulting white solid was collected by filtration

Sources & evidence

ORD record
ord-57c972e2571e4128beafca0945a9d180
Source dataset
uspto-grants-2001_03
Patent number
US06207160B1

Reaction notes

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