tert-Butyl piperazine-1-carboxylate → 8-(4-Tert-butoxycarbonyl-piperazin-1-yl)-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl ester

HRID 388276Notes

Reaction equation

HRID 388276 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].[CH2:53]([O:60][C:61]([N:63]1[C:68]2[CH:69]=[C:70]([Cl:74])[CH:71]=[C:72](Br)[C:67]=2[O:66][CH2:65][CH2:64]1)=[O:62])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1.[C:75]([O:79][C:80]([N:82]1[CH2:87][CH2:86][NH:85][CH2:84][CH2:83]1)=[O:81])([CH3:78])([CH3:77])[CH3:76]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[CH2:53]([O:60][C:61]([N:63]1[C:68]2[CH:69]=[C:70]([Cl:74])[CH:71]=[C:72]([N:85]3[CH2:84][CH2:83][N:82]([C:80]([O:79][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:81])[CH2:87][CH2:86]3)[C:67]=2[O:66][CH2:65][CH2:64]1)=[O:62])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

Participants

8

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 207656808-Bromo-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl esterHCID 23676156Sodium t-butoxide

Product 1

HCID 207656828-(4-Tert-butoxycarbonyl-piperazin-1-yl)-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A three neck flask was charge with tris(dibenzylideneacetone)dipalladium(0) (21.5 mg, 0.024 mmol, 2 mol % Pd), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (36.4 mg, 0.059 mmol, 5 mol %) and sodium-tert-butoxide (159 mg, 1.65 mmol) and flushed with nitrogen. A solution of 8-bromo-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl ester (450 mmg, 1.18 mmol) and piperazine-1-carboxylic acid tert-butyl ester (263 mg, 1.41 mmol) in toluene (2 mL) was added. The mixture was heated to 95° C. and was stirred for 12 hours. The mixture was cooled to room temperature, taken up in ethyl acetate, filtered through celite and concentrated. The crude material was purified by flash chromatography on silica gel (eluting with hexane-ethyl acetate; 7:3, v/v) to give 8-(4-tert-butoxycarbonyl-piperazin-1-yl)-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl ester a colorless oil (275 mg, 48%). MS: MH+=488.

Workup

  1. customflushed with nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through celite
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography on silica gel (
  6. washeluting with hexane-ethyl acetate

Sources & evidence

ORD record
ord-1aab0fc50ac2432a939ebbba1e3e5c60
Source dataset
uspto-grants-2013_02
Patent number
US08377931B2

Reaction notes

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