tert-Butyl piperazine-1-carboxylate → HCID 69418500, compound

HRID 1373547Notes

Reaction equation

HRID 1373547 reaction equation
C1(P(C2C=CC=CC=2C2C=CC=CC=2)C2CCCCC2)CCCCC1.Br[C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][C:35]=2[F:37])[CH:30]=[CH:29][CH:28]=1.[C:38]([N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:41]([O:40][C:38]([N:45]1[CH2:50][CH2:49][N:48]([C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][C:35]=3[F:37])[CH:30]=[CH:29][CH:28]=2)[CH2:47][CH2:46]1)=[O:39])([CH3:44])([CH3:42])[CH3:43]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 179956971-Bromo-8-fluoronaphthaleneHCID 23676156Sodium t-butoxide

Product 1

HCID 69418500HCID 69418500, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

A third intermediate compound, 1-(8-Fluoro-naphthalen-1-yl)-piperazine, was produced as follows: A solution of Pd(OAc)2 (0.25 g, 1.11 mmol, 0.1 equiv)) and dicyclohexylphosphino-biphenyl (0.39 g, 1.11 mmol, 0.1 equiv) in toluene (20 mL) was degassed by bubbling N2 gas for 1 h. 1-Bromo-8-fluoro-naphthalene (2.5 g, 11.1 mmol) in toluene (10 mL) and 1-Boc-piperazine (2.5 g, 13.3 mmol, 1.2 equiv) were added followed by NaOtBu (1.6 g, 16.66 mmol, 1.5 equiv). The mixture was stirred at 80° C. for 18 h. The solvent was removed under reduced pressure and the residue was taken in dichloromethane and filtered through a celite pad. The celite was rinsed with dichloromethane and the combined filtrates were concentrated. The residue was purified by silica gel chromatography (20% ethyl acetate in hexane) to give 4-(8-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester as a dark oil (1.4 g, 38%). 1H NMR (400 MHz, CDCl3): δ 7.60 (d, 1H), 7.50 (d, 1H), 7.40 (m, 1H), 7.10 (m, 2H), 6.95 (d, 1H), 4.50–4.00 (br s, 2H), 3.40–3.20 (m, 4H), 2.80–2.60 (m, 2H), 1.50 (s, 9H). MS (ES+): 331.08 (M+H)+.

Workup

  1. customby bubbling N2 gas for 1 h
  2. customThe solvent was removed under reduced pressure
  3. filtrationfiltered through a celite pad
  4. washThe celite was rinsed with dichloromethane
  5. concentrationthe combined filtrates were concentrated
  6. customThe residue was purified by silica gel chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-dac6b2b682db40419105a9c66ecf6f5e
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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