Ethanolamine → (s)-1,4-Dibenzyl-2-(2-(4-methoxy-phenyl)-ethyl)-piperazine

HRID 1350371Notes

Reaction equation

HRID 1350371 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH:21]=[CH2:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C12BC(CCC1)CCC2.I[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+].C(CN)O>O.C(O)(=O)C.CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:21][CH2:22][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 6

HCID 700EthanolamineHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 696764-IodoanisoleHCID 789669-Borabicyclo(3.3.1)nonaneHCID 17759473(S)-1,4-dibenzyl-2-vinylpiperazine

Product 1

HCID 69486828(s)-1,4-Dibenzyl-2-(2-(4-methoxy-phenyl)-ethyl)-piperazine

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 10129899Acetic acid methanolSolvent

Conditions

Temperature
60 °C

Procedure

Combine (S)-1,4-dibenzyl-2-vinyl-piperazine (2.0 g, 6.84 mmol) and 9-borabicyclo[3.3.1]nonane (82.1 mL, 41.04 mmol, 0.5 M in THF) and stir at ambient temperature. After 6 hours and 30 minutes, add 1-iodo-4-methoxy-benzene (2.4 g, 10.26 mmol), triphenylphosphine (287.0 mg, 1.09 mmol), tetrakis(triphenylphosphine) palladium(0)(158.0 mg, 0.14 mmol), and 3N NaOH (5.6 mL) and stir at 60° C. After 22 hours, add ethanolamine (10.0 ml) and dilute the mixture with water. Extract with ethyl acetate and combine, wash (brine), dry (sodium sulfate), and reduce the extracts to residue. Purify the residue on silica gel using ethyl acetate/hexanes (5:95) to give a yellow oil. Dissolve the yellow oil in acetic acid/methanol (1:9) and apply to an SCX column. Wash the column with methanol followed by 7N ammonia in methanol to give the title compound: mp 88–91° C.; mass spectrum (ion spray): m/z=401.4 (M+1).

Workup

  1. waitAfter 22 hours
  2. extractionExtract with ethyl acetate and combine
  3. washwash (brine)
  4. dry with materialdry (sodium sulfate)
  5. customPurify the residue on silica gel
  6. customto give a yellow oil
  7. washWash the column with methanol

Sources & evidence

ORD record
ord-86ea9e5605204412978501ab6050105d
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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