Benzyl chloroformate → HCID 118451586, compound

HRID 63709Notes

Reaction equation

HRID 63709 reaction equation
Cl.[NH2:2][C:3]1[C:12]2[N:13]=[C:14]([CH2:21][O:22][CH2:23][CH3:24])[N:15]([CH2:16][C:17]([OH:20])([CH3:19])[CH3:18])[C:11]=2[C:10]2[CH:9]=[CH:8][C:7]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:6][C:5]=2[N:4]=1.CCN([CH:38]([CH3:40])[CH3:39])C(C)C.Cl[C:42]([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43]>ClCCl>[CH2:45]([O:44][C:42]([N:2]([C:27]([O:29][CH2:30][C:39]1[CH:38]=[CH:40][CH:6]=[CH:5][CH:10]=1)=[O:28])[C:3]1[C:12]2[N:13]=[C:14]([CH2:21][O:22][CH2:23][CH3:24])[N:15]([CH2:16][C:17]([OH:20])([CH3:19])[CH3:18])[C:11]=2[C:10]2[CH:9]=[CH:8][C:7]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:6][C:5]=2[N:4]=1)=[O:43])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 81531DiisopropylethylamineHCID 118451621HCID 118451621, compound

Product 1

HCID 118451586HCID 118451586, compoundYield 202.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of ethyl 3-(4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl)propanoate hydrochloride (300 mg, 665 μmol) DMAP (15 mg, 123 μmol) and DIEA (1.86 ml, 10.6 mmol) in dichloromethane (6 mL), benzyl chloroformate (380 μl, 2.66 mmol) was added. The reaction mixture stirred at room temperature for 20 h, more benzyl chloroformate (908 60 μl, 5.32 mmol) was added and stirring continued for another 6 h. Afterwards the mixture was poured into dichloromethane (50 mL), extracted with HCl (1M, 20 mL) and water (20 mL). The aqueous layer was extracted with dichloromethane (50 mL), organic phases were combined, dried with MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 0% to 100% ethyl acetate in heptane) to give the title compound (0.459 g, quant.) as colorless oil; LC-MS (UV peak area, ESI) 86%, 683.5 (MH+).

Workup

  1. additionwas added
  2. stirringstirring
  3. waitcontinued for another 6 h
  4. extractionextracted with HCl (1M, 20 mL) and water (20 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane (50 mL), organic phases
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-779fba3df94540728248a4e955418fdf
Source dataset
uspto-grants-2016_09
Patent number
US09447097B2

Reaction notes

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