Diisopropylethylamine → (4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-benzo[b]thiophen-2-yl]-methanone

HRID 493181Notes

Reaction equation

HRID 493181 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:22]=[CH:21][C:14]3[S:15][C:16]([C:18](O)=[O:19])=[CH:17][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl.[F:24][C:25]1([F:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]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>[F:24][C:25]1([F:31])[CH2:30][CH2:29][N:28]([C:18]([C:16]2[S:15][C:14]3[CH:21]=[CH:22][C:11]([O:10][CH:7]4[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]4)=[CH:12][C:13]=3[CH:17]=2)=[O:19])[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 687282875-(1-Isopropyl-piperidin-4-yloxy)-benzo[b]thiophene-2-carboxylic acid

Product 1

HCID 68878185(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-benzo[b]thiophen-2-yl]-methanoneYield 64.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a flask were mixed together the above prepared 5-(1-isopropyl-piperidin-4-yloxy)-benzo[b]thiophene-2-carboxylic acid (0.128 g, 0.333 mmol, corrected for purity), 4,4-difluoropiperidine hydrochloride (0.063 g, 1.2 eq.), (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (0.181 g, 1.23 eq.) and 2.4 eq. of N-ethyldiisopropylamine (0.225 mL) in 1.3 mL of abs. THF and allowed to react during one night at ambient temperature. Pouring onto crashed ice/AcOEt/NH4Cl-solution, twofold extraction with AcOEt, washing with water, drying over sodium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, NEt3/AcOEt=4/96) produced 0.091 g of the title compound as light yellow solid.

Workup

  1. additionIn a flask were mixed together the
  2. customto react during one night at ambient temperature
  3. additionPouring
  4. extractionextraction with AcOEt
  5. washwashing with water
  6. dry with materialdrying over sodium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-cc912a2ced614b3a8f8bf5cafec2bd33
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

Loading…