Benzyl chloroformate → HCID 18677361, compound

HRID 1634146Notes

Reaction equation

HRID 1634146 reaction equation
[C:1]([CH2:4][N:5]1[C:10]([CH3:11])=[CH:9][N:8]=[C:7]([NH:12][NH2:13])[C:6]1=[O:14])([OH:3])=[O:2].C([O-])(O)=O.[Na+].[CH2:20]([O:27][C:28](Cl)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O.O1CCOCC1>[CH2:20]([O:27][C:28]([NH:13][NH:12][C:7]1[C:6](=[O:14])[N:5]([CH2:4][C:1]([OH:3])=[O:2])[C:10]([CH3:11])=[CH:9][N:8]=1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 18677360HCID 18677360, compound

Product 1

HCID 18677361HCID 18677361, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of the compound of Example 5 (Step G) (5.0 g, 0.025 mol) and NaHCO3 (9.4 g, 0.112 mol) in water (180 mL), was added drop-wise a solution of benzylchloroformate (6.0 mL, 0.042 mol) in dioxane (300 mL). The resulting mixture was stirred at room temperature for 4 hours, diluted with water (200 mL), and washed with ether (200 mL). The aqueous phase was acidified with aqueous 2M KHSO4 and extracted with EtOAc (3×300 mL). The combined organic phases were washed with brine (400 mL), dried (Na2SO4), and concentrated in vacuo. The crude mixture was purified by flash chromatography on silica gel to afford the title compound (7.35 g, 90%) as a pale brown solid. 1H NMR (DMSO-d4) δ 2.15 (s, 3H), 4.3 (br s, 1H), 4.73 (s, 2H), 5.12 (s, 2H), 6.76 (s, 1H), 7.20-7.50 (m, 5H), 9.7 (br s, 1H), 10.0 (br s, 1H). HPLC Rt 8.10 minutes (water/ACN/TFA, 5 to 75%, 0.1% TFA, 20 minutes).

Workup

  1. washwashed with ether (200 mL)
  2. extractionextracted with EtOAc (3×300 mL)
  3. washThe combined organic phases were washed with brine (400 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-4a89818458454245849ec47afb24d291
Source dataset
uspto-grants-2003_01
Patent number
US06506760B1

Reaction notes

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