Methanol → 1-Boc-4-(4-methoxycarbonylphenyl)piperazine

HRID 54221Notes

Reaction equation

HRID 54221 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17](OS(C(F)(F)F)(=O)=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:35][OH:36].CN(C)[CH:39]=[O:40]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:35]([O:40][CH3:39])=[O:36])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 199585131-(tert-Butoxycarbonyl)-4-(4-trifluoromethanesulfonyloxyphenyl)piperazine

Product 1

HCID 27955131-Boc-4-(4-methoxycarbonylphenyl)piperazineYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(tert-butoxycarbonyl)-4-(4-trifluoromethanesulfonyloxyphenyl)piperazine (1.92 g, 4.68 mmol), palladium (II) acetate (52.5 mg, 0.23 mmol), 1,1'-bis(diphenylphosphino)ferrocene (325.0 mg, 0.59 mmol), triethylamine (1.3 ml, 9.33 mmol), methanol (8 ml) and dimethylformamide (20 ml) was purged with carbon monoxide for 15 minutes, sealed under a balloon of carbon monoxide and stirred at 60° C. overnight (18 hours). The reaction mixture was allowed to cool, concentrated in vacuo to a small volume and the residue triturated with ethyl acetate. The solid was collected, washed with ethyl acetate and dried to give the title compound (0.659 g, 44%), as a pale cream solid. Evaporation of the ethyl acetate mother liquors and purification of the residue by flash chromatography (eluting with 5% to 10% ethyl acetate in dichloromethane) gave more of the title compound (0.492 g, 33%); δH (CDCl3) 1.49 (9H, s, C(CH3)3), 3.31 (4H, m, 2×piperazinyl CH2), 3.60 (4H, m, 2×piperazinyl CH2), 3.87 (3H, s, CO2CH3), 6.89 (2H, m, ArH), and 7.94 (2H, m, ArH).

Workup

  1. customwas purged with carbon monoxide for 15 minutes
  2. customsealed under a balloon of carbon monoxide
  3. temperatureto cool
  4. concentrationconcentrated in vacuo to a small volume
  5. customthe residue triturated with ethyl acetate
  6. customThe solid was collected
  7. washwashed with ethyl acetate
  8. customdried

Sources & evidence

ORD record
ord-d14f110c52d1445f94c0dcd0d3eb9412
Source dataset
uspto-grants-1997_04
Patent number
US05622950

Reaction notes

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