Triphenylphosphine → 4-(2-Ethoxycarbonyl-benzo[b]thiophen-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 493197Notes

Reaction equation

HRID 493197 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]2[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26](O)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].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:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:15][C:12]2[CH:13]=[CH:14][C:8]3[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[S:10][C:9]=3[CH:11]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 58047243Ethyl 6-hydroxybenzo[b]thiophene-2-carboxylate

Product 1

HCID 687265814-(2-Ethoxycarbonyl-benzo[b]thiophen-6-yloxy)-piperidine-1-carboxylic acid tert-butyl esterYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The above prepared 6-hydroxy-benzo[b]thiophene-2-carboxylic acid ethyl ester (0.206 g, 0.927 mmol, see example 7, step 1 and 2) was dissolved in 5 mL of THF and treated successively at −10° C. with 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.261 g, 1.4 eq.), triphenylphosphine (0.340 g, 1.4 eq.) and DIAD (0.255 mL, 2 eq.), and the mixture then kept at ambient temperature over night. Pouring onto crashed ice, 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), yielded 0.355 g of the title compound as colorless gum.

Workup

  1. waitthe mixture then kept at ambient temperature over night
  2. additionPouring
  3. extractionice, twofold extraction with AcOEt
  4. washwashing with water and brine
  5. dry with materialdrying over magnesium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-f4fc7e9fcad54b32879d46e56b223619
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

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