Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate → Ethyl 4-(2-(4-(4-(1,1-dimethylethoxycarbonyl)piperazinyl)phenyl)ethenyl)phenoxyacetate

HRID 1459436Notes

Reaction equation

HRID 1459436 reaction equation
[Br-].[CH2:2]([O:4][C:5]([CH2:7][O:8][C:9]1[CH:34]=[CH:33][C:12]([CH2:13][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:11][CH:10]=1)=[O:6])[CH3:3].[CH3:35][C:36]([CH3:55])([O:38][C:39]([N:41]1[CH2:46][CH2:45][N:44]([C:47]2[CH:54]=[CH:53][C:50]([CH:51]=O)=[CH:49][CH:48]=2)[CH2:43][CH2:42]1)=[O:40])[CH3:37]>C1COCC1>[CH3:37][C:36]([CH3:55])([O:38][C:39]([N:41]1[CH2:42][CH2:43][N:44]([C:47]2[CH:48]=[CH:49][C:50]([CH:51]=[CH:13][C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:5]([O:4][CH2:2][CH3:3])=[O:6])=[CH:34][CH:33]=3)=[CH:53][CH:54]=2)[CH2:45][CH2:46]1)=[O:40])[CH3:35]

Participants

4

Reactant 2

HCID 2795509Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylateHCID 867534784-(Ethoxycarbonylmethoxy)benzyltriphenylphosphonium bromide

Product 1

HCID 53769651Ethyl 4-(2-(4-(4-(1,1-dimethylethoxycarbonyl)piperazinyl)phenyl)ethenyl)phenoxyacetateYield 103.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To an oven dried 100 mL round bottomed flask with a stirring bar and an argon inlet was added 4-(ethoxycarbonylmethoxy)benzyltriphenyl-phosphonium bromide (1.106 g, 2.07 mmol) and dry THF (50 mL). To this well stirred mixture was added a solution of lithium hexamethyldisilylazide (2.20 mL of a 1M solution in THF). The deep red solution was stirred 1 h at ambient temperature then cooled in an ice bath to 0° C. To this mixture was added a solution of 4-(4-(1,1-dimethylethoxycarbonyl)piperazinyl)benzaldehyde (0.60 g, 2.07 mmol) in 10 mL of THF. The ice bath was removed and the solution was stirred at ambient temperature for 3 h. The reaction mixture was diluted with EtOAc and washed with water and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave 1 g of an oil. This material was chromatographed on 80 g of silica gel using 25% EtOAc-hexane as eluant. There was obtained (E)-ethyl 4-(2-(4-(4-(1,1-dimethylethoxycarbonyl)piperazinyl)phenyl)ethenyl)phenoxyacetate 35-7 as an oil. 1H NMR (CDCl3): δ 1.26 (t, j=7 Hz, 3H), 1.49 (s, 9H), 3.16 (m, 4H), 3.57 (m, 4H), 4.27 (q, j=7 Hz, 2H), 4.60 (s, 2H), 6.90 (m, 6H), 7.40 (m, 4H), and 175 mg of a mixture of E,Z isomers.

Workup

  1. customTo an oven dried 100 mL round bottomed flask with a stirring bar and an argon inlet
  2. stirringThe deep red solution was stirred 1 h at ambient temperature
  3. customThe ice bath was removed
  4. stirringthe solution was stirred at ambient temperature for 3 h
  5. additionThe reaction mixture was diluted with EtOAc
  6. washwashed with water and brine
  7. customDrying
  8. filtration(MgSO4), filtration and removal of the solvent in vacuo

Sources & evidence

ORD record
ord-e39d3532853d41f1a17cf49df6d5920f
Source dataset
uspto-grants-1998_12
Patent number
US05854245

Reaction notes

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