3-Chloro-4-methoxybenzeneboronic acid → 4-(3-Chloro-4-methoxy-benzoyl)-piperidine-1-carboxylic acid tert-butylester

HRID 713458

Reaction equation

HRID 713458 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[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]>C1COCC1.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](=[O:27])[C:4]2[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 2

HCID 32475223-Chloro-4-methoxybenzeneboronic acidHCID 893758004-Phenylsulfanylcarbonyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 712360784-(3-Chloro-4-methoxy-benzoyl)-piperidine-1-carboxylic acid tert-butylesterYield 88.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-chloro-4-methoxyphenylboronic acid (0.87 g, 4.67 mmol), ligand TFP (0.14 g, 0.6 mmol), Pd2dba3 (0.29 g, 0.31 mmol), copper (I) thiophene-2-carboxylate (0.89 g, 4.7 mmol) was added a solution of 4-phenylsulfanylcarbonyl-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 3.1 mmol) in 10 mL of THF 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 (1.02 g, 2.74 mmol). MS (ESI) m/z 354.0 (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 1.42 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-f5519f890ff84bf9bf6ab184dfd0df64
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Linked notes

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