Toluene → HCID 86701437, compound

HRID 2173902Notes

Reaction equation

HRID 2173902 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:8]2[NH:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.O[CH2:22][CH2:23][NH:24][C:25](=[O:34])[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(P(CCCC)CCCC)CCC.CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1>C1COCC1.C([O-])(O)=O.[Na+]>[CH2:27]([O:26][C:25]([NH:24][CH2:23][CH2:22][O:1][C:2]1[CH:3]=[C:4]([CH:8]2[NH:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1)=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 13831TributylphosphineHCID 280458benzyl N-(2-hydroxyethyl)carbamateHCID 5462977Diethyl azodicarboxylateHCID 16740841tert-Butyl 3-(3-hydroxyphenyl)piperazine-1-carboxylate

Product 1

HCID 86701437HCID 86701437, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

(+) or (−)-tert-butyl 3-(3-hydroxyphenyl)piperazine-1-carboxylate (tr=9.7 min) (Biological Example 2.1) (300 mg, 1.078 mmol) and benzyl 2-hydroxyethylcarbamate (210 mg, 1.078 mmol) were dissolved in THF (10 ml). Tributylphosphine (0.404 ml, 1.617 mmol) was added, and after cooling to 0° C., DEAD 40% in toluene (0.640 ml, 1.617 mmol) was added dropwise. The reaction was stirred for 2 h at 0° C., then overnight at rt. The reaction mixture was diluted with aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with AcOEt. The organic phase dried over MgSO4 and concentrated in vacuum. The crude residue was purified by preparative HPLC (Macherey-Nagel Nucleosil 100-10 C18, CH3CN/H2O (0.1% TFA)) to give the title compound. MS (ESI+) m/z 455.2 (M+H).

Workup

  1. customovernight
  2. customat rt
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with AcOEt
  5. dry with materialThe organic phase dried over MgSO4
  6. concentrationconcentrated in vacuum
  7. customThe crude residue was purified by preparative HPLC (Macherey-Nagel Nucleosil 100-10 C18, CH3CN/H2O (0.1% TFA))

Sources & evidence

ORD record
ord-36dea08cbee04e1c926400742e09417b
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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