tert-butyl(2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate → tert-butyl (2R)-2-({[7-(benzyloxy)-4-oxo-3,4-dihydroquinazolin-5-yl]oxy}methyl)pyrrolidine-1-carboxylate

HRID 1442990Notes

Reaction equation

HRID 1442990 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:27])[N:14](COC(=O)C(C)(C)C)[CH:15]=[N:16]2)=[C:11]([O:28][CH2:29][C@H:30]2[CH2:34][CH2:33][CH2:32][N:31]2[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>N.CO.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:27])[NH:14][CH:15]=[N:16]2)=[C:11]([O:28][CH2:29][C@H:30]2[CH2:34][CH2:33][CH2:32][N:31]2[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 1

HCID 69638708tert-butyl(2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate

Product 1

HCID 136344270tert-butyl (2R)-2-({[7-(benzyloxy)-4-oxo-3,4-dihydroquinazolin-5-yl]oxy}methyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

The crude tert-butyl (2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]-methyl}4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate (assumed 18 g) was dissolved in 7N ammonia in methanol and stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and purified by column chromatography using 0-10% methanol in DCM as eluent to give a mixture of two products. The mixture was dissolved in DCM, washed with 20% aqueous sodium hydroxide solution (2×) and then dried (MgSO4) and concentrated in vacuo to leave tert-butyl (2R)-2-({[7-(benzyloxy)-4-oxo-3,4-dihydroquinazolin-5-yl]oxy}methyl)pyrrolidine-1-carboxylate as a beige foam (6.8 g, 48% for the two steps); Mass spectrum MH+ 452.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by column chromatography
  3. customto give
  4. additiona mixture of two products
  5. washwashed with 20% aqueous sodium hydroxide solution (2×)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6f9dbe2fb89b43cba5b83ccba98f1128
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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