(2,3-Dihydro-1-benzofuran-5-yl)boronic acid → 4-(2,3-Dihydro-benzofuran-5-carbonyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 713420

Reaction equation

HRID 713420 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8](B(O)O)=[CH:9][C:4]=2[CH2:3][CH2:2]1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([C:26](SC2C=CC=CC=2)=[O:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].S1C=CC=C1C([O-])=O.[Cu+]>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([C:26]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][CH2:3][C:4]=3[CH:9]=2)=[O:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 2

HCID 2773380(2,3-Dihydro-1-benzofuran-5-yl)boronic acidHCID 893758004-Phenylsulfanylcarbonyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 712269604-(2,3-Dihydro-benzofuran-5-carbonyl)-piperidine-1-carboxylic acid tert-butyl esterYield 89.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 2,3-dihydro-1-benzofuran-5-ylboronic acid (0.56 g, 1.56 mmol), ligand TFP (0.07 g, 0.3 mmol), Pd2dba3 (0.28 g, 0.30 mmol), copper (I) thiophene-2-carboxylate (0.45 g, 2.4 mmol) was added a solution of 4-phenylsulfanylcarbonyl-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 1.6 mmol) in 15 mL of DME while purging with N2 at 50° C. After 18 hours the reaction mixture was diluted with ethyl acetate, filtered through celite then concentrated in vacuo. Purification by flash chromatography gave the title compound (0.5 g, 1.4 mmol, 87% yield). MS (ESI) m/z 331.8 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) t 1.54 min.

Workup

  1. customwhile purging with N2 at 50° C
  2. additionAfter 18 hours the reaction mixture was diluted with ethyl acetate
  3. filtrationfiltered through celite
  4. concentrationthen concentrated in vacuo
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-c8f286941442437f9c0c04f92f909969
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Linked notes

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