tert-Butyl piperazine-1-carboxylate → 4-(2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 459799Notes

Reaction equation

HRID 459799 reaction equation
Br[C:2]1[C:11]2[CH2:10][O:9][C:8](=[O:12])[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:13]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:16]([O:15][C:13]([N:20]1[CH2:25][CH2:24][N:23]([C:2]2[C:11]3[CH2:10][O:9][C:8](=[O:12])[NH:7][C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:22][CH2:21]1)=[O:14])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 184445205-Bromo-1H-benzo[d][1,3]oxazin-2(4H)-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 588241374-(2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-5-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 31%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 5-bromo-1,4-dihydro-benzo[d][1,3]oxazin-2-one (96 mg, 0.42 mmol) and 1-Boc-piperazine (100 mg, 0.54 mmol) in 2 ml toluene was added to a mixture of Pd2(dba)3 (8 mg, 0.009 mmol), BINAP (13 mg, 0.022 mmol), NaOt-Bu (121 mg, 1.26 mmol). With stirring, the solution was heated at 95° C.–100° C. for 4 hours and was allowed to cool to room temperature. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and the resulting brown residue was purified by prep TLC to give 43 mg 4-(2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester as a yellow solid (31%).

Workup

  1. temperaturethe solution was heated at 95° C.–100° C. for 4 hours
  2. filtrationThe reaction mixture was filtered through celite
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with water and brine
  5. dry with materialAfter drying over MgSO4
  6. concentrationthe organic fraction was concentrated in vacuo
  7. customthe resulting brown residue was purified by prep TLC

Sources & evidence

ORD record
ord-ecb4a00ad89e4aafb68bb986c4f86c0b
Source dataset
uspto-grants-2007_03
Patent number
US07196087B2

Reaction notes

Loading…