tert-Butyl piperazine-1-carboxylate → HCID 89494226, compound

HRID 2209270Notes

Reaction equation

HRID 2209270 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([O:9][CH3:10])[CH:3]=1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:14]2[CH2:13][CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15]2)=[C:4]([O:9][CH3:10])[CH:3]=1

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 468357314-Bromo-1-iodo-2-methoxybenzene

Product 1

HCID 89494226HCID 89494226, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
45 °C

Procedure

4-bromo-1-iodo-2-methoxybenzene (647 mg, 2.07 mmol), tert-butyl piperazine-1-carboxylate (350 mg, 1.88 mmol), sodium tert-butoxide (541 mg, 5.6 mmol), Pd2(dba)3 (52 mg, 0.056 mmol) and XantPhos (98 mg, 0.17 mmol) were taken up in toluene (18 mL) under Ar. The reaction mixture was stirred for 18 h and was then heated to 45° C. After an additional 2.5 h, the temperature was increased to 65° C. After an additional 3 h, the reaction mixture was cooled and partitioned between water and EtOAc. The phases were separated, and the organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (0-25% EtOAc in hexanes) to afford tert-butyl 4-(4-bromo-2-methoxyphenyl)piperazine-1-carboxylate 7.09. LCMS-ESI+ (m/z): [M-41]+ calcd for C16H24BrN2O3: 371.1; found: 370.8.

Workup

  1. waitAfter an additional 2.5 h
  2. temperaturethe temperature was increased to 65° C
  3. waitAfter an additional 3 h
  4. temperaturethe reaction mixture was cooled
  5. custompartitioned between water and EtOAc
  6. customThe phases were separated
  7. dry with materialthe organic phase was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by silica gel chromatography (0-25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-eb19eae67d654ac4a7c16400efe1aa49
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…