tert-Butyl piperazine-1-carboxylate → HCID 69419217, compound

HRID 1373548Notes

Reaction equation

HRID 1373548 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](OS(C(F)(F)F)(=O)=O)=[CH:7][CH:6]=[CH:5]2.[C:20]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:23]([O:22][C:20]([N:27]1[CH2:32][CH2:31][N:30]([C:8]2[C:9]3[C:4](=[CH:3][C:2]([F:1])=[CH:11][CH:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:29][CH2:28]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 179336066-Fluoronaphthalen-1-yl trifluoromethanesulfonateHCID 23676156Sodium t-butoxide

Product 1

HCID 69419217HCID 69419217, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A fourth intermediate compound, 1-(6-Fluoro-naphthalen-1-yl)-piperazine, was produced as follows: Trifluoro-methanesulfonic acid 6-fluoro-naphthalen-1-yl ester (1.24 g, 4.23 mmol) and 1-Boc-piperazine (946 mg, 5.08 mmol) were dissolved in toluene (15 mL) and the mixture was degassed for 30 minutes. To this was added 2-(dicyclohexylphosphino)-biphenyl (148 mg, 0.42 mmol), palladium acetate (95 mg, 0.42 mmol), and sodium tert-butoxide (569 mg, 5.92 mmol). The mixture was stirred at 80° C. for 30 minutes, then cooled to room temperature, washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude oil was filtered through a short plug of silica gel, eluting with 3:1 hexanes/ethyl acetate to yield crude 4-(6-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester as a brown oil. The crude oil was dissolved in a mixture of dichloromethane (5 mL) and trifluoroacetic acid (5 mL) and stirred at room temperature for 4 hours. The mixture was evaporated in vacuo and diethyl ether (30 mL) was added. The grey precipitate was filtered off and rinsed with diethyl ether (20 mL) to yield the fourth intermediate compound as the TFA salt (755 mg, 52%) as a grey solid. 1H NMR (400 MHz, dmso-d6) δ 8.80 (s, 1H), 8.24–8.18 (m, 1H), 7.72 (d, 1H), 7.68 (d, 1H), 7.50 (t, 1H), 7.40 (t, 1H), 7.18 (d, 1H), 3.40–3.10 (m, 8H).

Workup

  1. customthe mixture was degassed for 30 minutes
  2. temperaturecooled to room temperature
  3. washwashed with water (20 mL) and brine (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationThe crude oil was filtered through a short plug of silica gel
  8. washeluting with 3:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-0a7b4769fa7b455790e67eb81a819a3c
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

Loading…