Triphenylphosphine → 5-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid ethyl ester

HRID 493221Notes

Reaction equation

HRID 493221 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].[CH:18]([N:21]1[CH2:26][CH2:25][CH:24](O)[CH2:23][CH2:22]1)([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>[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[C:14]([O:16][CH:24]3[CH2:25][CH2:26][N:21]([CH:18]([CH3:20])[CH3:19])[CH2:22][CH2:23]3)[C:13]([Cl:17])=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 796811-Isopropylpiperidin-4-olHCID 5363146Diisopropyl azodicarboxylateHCID 687242575-Chloro-6-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester

Product 1

HCID 687236245-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid ethyl esterYield 94.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The above prepared 5-chloro-6-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester (0.700 g, 2.75 mmol) was dissolved in 12 mL of THF and treated successively at −10° C. with 1-isopropyl-piperidin-4-ol (0.551 g, 1.4 eq.), triphenylphosphine (1.001 g, 1.4 eq.) and DIAD (0.755 mL, 1.4 eq.), and the mixture then kept at ambient temperature for another 4 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, NEt3/AcOEt=2/98), produced 0.990 g of the title compound as light yellow 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-0d504c4eecf64e069f6c3c3da0c24b7f
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

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