Triphenylphosphine → 4-(5-Chloro-2-ethoxycarbonyl-3-methyl-benzofuran-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 493224Notes

Reaction equation

HRID 493224 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[C:14]([OH:16])[C:13]([Cl:17])=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5])[CH3:2].[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28](O)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([O:16][C:14]2[C:13]([Cl:17])=[CH:12][C:9]3[C:10]([CH3:11])=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[O:7][C:8]=3[CH:15]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 687242575-Chloro-6-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester

Product 1

HCID 688787714-(5-Chloro-2-ethoxycarbonyl-3-methyl-benzofuran-6-yloxy)-piperidine-1-carboxylic acid tert-butyl esterYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The above prepared 5-chloro-6-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (0.900 g, 3.53 mmol) was dissolved in 15 mL of THF and treated successively at −10° C. with 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.996 g, 1.4 eq.), triphenylphosphine (1.298 g, 1.4 eq.) and DIAD (0.971 mL, 1.4 eq.), and the mixture then kept at ambient temperature for another 3 h. Pouring onto crashed ice/NH4Cl, twofold extraction with AcOEt, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/AcOEt=85/15), gave 1.459 g of the title compound as colorless gum.

Workup

  1. additionPouring
  2. extractionice/NH4Cl, twofold extraction with AcOEt
  3. washwashing with water and brine
  4. dry with materialdrying over magnesium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-af1abfdc1e414f1da2aace33ddf8df80
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

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