tert-Butyl piperazine-1-carboxylate → HCID 67026375, compound

HRID 713810Notes

Reaction equation

HRID 713810 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:19]1([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>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]>[N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:10]2[N:9]=[C:8]([C:4]3[CH:3]=[C:2]([N:22]4[CH2:21][CH2:20][N:19]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23]4)[CH:7]=[CH:6][CH:5]=3)[O:12][N:11]=2)[CH:14]=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 878411HCID 878411, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 67026375HCID 67026375, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of the product of Example 63 (200 mg, 0.66 mmol) and tert-butyl piperazine-1-carboxylate (Aldrich, 123 mg, 0.66 mmol) in toluene (anhydrous, 10 mL) was degassed and purged with nitrogen three times, sodium t-butoxide (Aldrich, 64 mg, 0.66 mmol) and tris(dibenzylideneacetone)dipalladium(0) (Aldrich, 12.1 mg, 0.013 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Aldrich, 23.0 mg, 0.040 mmol, xantphos) were added, degassed and purged with nitrogen three times. The mixture was then heated to 100° C. and stirred under nitrogen for 15 hours. It was then cooled to ambient temperature and diluted with ethyl acetate (50 mL), washed with brine (2×5 mL), concentrated, purified with chromatography (v. ethyl acetate/hexane=1/1, Rf=0.6) to give the title compound. 1H NMR (300 MHz, MeOH-d4) δ 1.49 (s, 9H), 3.25-3.30 (m, 4H), 3.56-3.71 (m, 4H), 7.31 (ddd, J=8.4, 2.6, 0.8 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.64 (ddd, J=8.0, 4.9, 0.7 Hz, 1H), 7.70 (dt, J=8.0, 1.1 Hz, 1H), 7.79 (dd, J=2.4, 1.7 Hz, 1H), 8.56 (dt, J=7.9, 2.0 Hz, 1H), 8.74 (dd, J=4.9, 1.5 Hz, 1H), 9.29 (dd, J=2.2, 0.8 Hz, 1H) ppm; MS (DCl/NH3) m/z 408 (M+H)+.

Workup

  1. additionwere added
  2. customdegassed
  3. custompurged with nitrogen three times
  4. temperatureIt was then cooled to ambient temperature
  5. additiondiluted with ethyl acetate (50 mL)
  6. washwashed with brine (2×5 mL)
  7. concentrationconcentrated
  8. custompurified with chromatography (v. ethyl acetate/hexane=1/1, Rf=0.6)

Sources & evidence

ORD record
ord-2c52d4823242462b8f05909d4be9eff7
Source dataset
uspto-grants-2015_11
Patent number
US09186407B2

Reaction notes

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