Diisopropylethylamine → (4,4-Difluoro-piperidin-1-yl)-[6-(1-isopropyl-piperidin-4-yloxy)-benzo[b]thiophen-2-yl]-methanone

HRID 493186Notes

Reaction equation

HRID 493186 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[CH:18]=[C:17]([C:19]([OH:21])=O)[S:16][C:15]=3[CH:22]=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:19]([C:17]2[S:16][C:15]3[CH:22]=[C:11]([O:10][CH:7]4[CH2:6][CH2:5][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:9][CH2:8]4)[CH:12]=[CH:13][C:14]=3[CH:18]=2)=[O:21])[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 687277496-(1-Isopropyl-piperidin-4-yloxy)-benzo[b]thiophene-2-carboxylic acid

Product 1

HCID 68745278(4,4-Difluoro-piperidin-1-yl)-[6-(1-isopropyl-piperidin-4-yloxy)-benzo[b]thiophen-2-yl]-methanoneYield 76.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a flask were mixed together the above prepared 6-(1-isopropyl-piperidin-4-yloxy)-benzo[b]thiophene-2-carboxylic acid (0.147 g, 0.320 mmol, corrected for purity), 4,4-difluoropiperidine hydrochloride (0.060 g, 1.2 eq.), (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (0.170 g, 1.2 eq.) and 2.5 eq. of N-ethyldiisopropylamine (0.760 mL) in 2 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 and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, CH2Cl2/MeOH=9/1) produced 0.103 g of the title compound as white foam.

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 and brine
  6. dry with materialdrying over magnesium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-ee644f4f19694c97a1592629823ded48
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

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