Diisopropylethylamine → [5-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone

HRID 493223Notes

Reaction equation

HRID 493223 reaction equation
[Cl:1][C:2]1[C:3]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)=[CH:4][C:5]2[O:9][C:8]([C:10]([OH:12])=O)=[C:7]([CH3:13])[C:6]=2[CH:14]=1.Cl.[F:26][C:27]1([F:33])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C1COCC1>[Cl:1][C:2]1[C:3]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)=[CH:4][C:5]2[O:9][C:8]([C:10]([N:30]3[CH2:31][CH2:32][C:27]([F:33])([F:26])[CH2:28][CH2:29]3)=[O:12])=[C:7]([CH3:13])[C:6]=2[CH:14]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 687236205-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 68724082[5-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanoneYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a flask were mixed together the above prepared 5-chloro-6-(1-isopropyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid (0.200 g, 0.406 mmol, corrected for purity), 4,4-difluoropiperidine hydrochloride (0.077 g, 1.2 eq.), (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (0.216 g, 1.2 eq.) and 2.4 eq. of N-ethyldiisopropylamine (0.166 mL) in 4 mL of abs. THF and stirred over night at ambient temperature. Pouring onto crashed ice/AcOEt/NH4Cl-solution, 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) yielded 0.183 g of the title compound as white solid.

Workup

  1. additionIn a flask were mixed together the
  2. additionPouring
  3. extractionextraction 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-f1c4c54cb962482e9be32388a8bbddfc
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

Loading…