Benzyl chloroformate → HCID 18677363, compound

HRID 1634147Notes

Reaction equation

HRID 1634147 reaction equation
[C:1]([CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([Cl:12])[N:8]=[C:7]([NH:13][NH2:14])[C:6]1=[O:15])([OH:3])=[O:2].C([O-])(O)=O.[Na+].Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>O.O1CCOCC1>[CH2:25]([O:24][C:22]([NH:14][NH:13][C:7]1[C:6](=[O:15])[N:5]([CH2:4][C:1]([OH:3])=[O:2])[C:10]([CH3:11])=[C:9]([Cl:12])[N:8]=1)=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 18677357HCID 18677357, compound

Product 1

HCID 18677363HCID 18677363, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of the compound of Example 14 (1.9 g, 8.26 mmol) and NaHCO3 (2.08 g, 24.75 mmol) in water, (60 mL) was added drop-wise a solution of benzyl chloroformate (1.9 mL, 13.21 mmol) in dioxane (100 mL). The resulting mixture was stirred at room temperature for 4 hours, then was diluted with water (60 mL) and washed with ether (100 mL). The aqueous solution was acidified with 2 M KHSO4 and extracted with EtOAc (3×100 mL). The combined organic phases were washed with brine (200 mL), dried (Na2SO4), and concentrated in vacuo. The crude mixture was purified by flash chromatography on silica gel (1:1 EtOAc/hexane, then 9:1 DCM/MeOH) to afford the title compound (1.6 g, 53%) as a pale yellow solid. 1H NMR (DMSO-d4) δ 2.24 (s, 2H), 4.64 (s, 2H), 5.13 (s, 2H), 7.20-7.45 (m, 5H), 9.22 (s, 1H), 9.29 (s, 1H). HPLC Rt 11.4 minutes (water/ACN/TFA, 5 to 75%, 0.1% TFA, 20 minutes).

Workup

  1. washwashed with ether (100 mL)
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined organic phases were washed with brine (200 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by flash chromatography on silica gel (1:1 EtOAc/hexane

Sources & evidence

ORD record
ord-d35f625f0bfe4e3b903b2a8edef8fd06
Source dataset
uspto-grants-2003_01
Patent number
US06506760B1

Reaction notes

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