Diethyl azodicarboxylate → 4-[3-(4-Ethoxycarbonyl-2-fluoro-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 220840Notes

Reaction equation

HRID 220840 reaction equation
CCOC(/N=N/C(OCC)=O)=O.[CH2:13]([O:15][C:16](=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([F:24])[CH:18]=1)[CH3:14].[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][CH2:41]O)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][CH2:41][O:23][C:20]2[CH:21]=[CH:22][C:17]([C:16]([O:15][CH2:13][CH3:14])=[O:25])=[CH:18][C:19]=2[F:24])[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 5462977Diethyl azodicarboxylateHCID 13745619Ethyl 3-fluoro-4-hydroxybenzoateHCID 162178001-Boc-4-(3-hydroxypropyl)piperazine

Product 1

HCID 575554364-[3-(4-Ethoxycarbonyl-2-fluoro-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine polystyrene (loading 1.0 mmol/g, 11 g, 11.0 mmol) and DEAD (2.45 g, 11.0 mmol) were added to a solution of 3-fluoro-4-hydroxy-benzoic acid ethyl ester from Example E27 (1.3 g, 7.4 mmol) and 4-(3-hydroxy-propyl)-piperazine-1-carboxylic acid tert-butyl ester from Example E34 (1.8 g, 7.4 mmol) in tetrahydrofuran (100 ml) at 0° C. The suspension was allowed to warm to room temperature and stirred for 18 h. The mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; EtOAC) to yield the title compound (1.7 g, 57%).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate concentrated in vacuo
  3. customThe residue was purified by flash chromatography on silica gel (eluant; EtOAC)

Sources & evidence

ORD record
ord-89c49444c53b4548901757dd7e5da571
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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