Sodium Hydroxide → 1,1-Dimethylethyl 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate

HRID 884497

Reaction equation

HRID 884497 reaction equation
[C:1]([N:4]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([F:28])[F:27])=[CH:20][C:19]=1[C:29](OC)=[O:30])[CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)(=[O:3])[NH2:2].[OH-].[Na+]>O1CCOCC1>[F:27][CH:26]([F:28])[CH2:25][O:24][C:21]1[CH:20]=[C:19]2[C:18](=[CH:23][CH:22]=1)[N:4]([CH:5]1[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[CH2:9][CH2:10]1)[C:1](=[O:3])[NH:2][C:29]2=[O:30]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 595872271,1-Dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)-phenyl]amino}piperidine-1-carboxylate

Product 1

HCID 595871251,1-Dimethylethyl 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2.5 g of 1,1-dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate obtained in stage 3.4 in solution in a mixture of 10 ml of dioxane and 5 ml of a 1N aqueous NaOH solution are irradiated under a microwave field at 130° C. for 30 min. Extraction is carried out with AcOEt and the extract is neutralized with a 1N aqueous HCl solution, washed with water, dried over MgSO4, filtered and evaporated under reduced pressure. The residue obtained is triturated in an AcOEt/pentane mixture to give the expected product. The same reaction is reproduced with 2 other lots of 2.5 g of 1,1-dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate obtained in stage 3.4 to give, in total, 5.63 g of expected product.

Workup

  1. customare irradiated under a microwave field at 130° C. for 30 min
  2. extractionExtraction
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue obtained
  8. customis triturated in an AcOEt/pentane mixture

Sources & evidence

ORD record
ord-c980d0ccee024131b0d89f5c974f28e1
Source dataset
uspto-grants-2012_08
Patent number
US08242126B2

Linked notes

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