Diisopropylethylamine → Methyl 2-(4-(2-chloro-4-methylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

HRID 1399713Notes

Reaction equation

HRID 1399713 reaction equation
Cl[C:2]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:16])[N:5]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[N:3]=1.C(N(CC)C(C)C)(C)C.[Cl:32][C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[CH:35][C:34]=1B(O)O>COCCOC.O.[Cl-].[Na+].O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:32][C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[CH:35][C:34]=1[C:2]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:16])[N:5]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[N:3]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 2773334(2-Chloro-4-methylphenyl)boronic acidHCID 86665653Methyl 2-(4-chloro-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

Product 1

HCID 66955346Methyl 2-(4-(2-chloro-4-methylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoateYield 66.4%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 18180031Water 1,2-dimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of methyl 2-(4-chloro-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate (0.081 g; 0.25 mmol), tetrakis(triphenylphosphine) palladium(0) (0.029 g; 0.025 mmol), N,N-diisopropylethylamine (0.172 mL; 1.00 mmol) and 2-chloro-4-methylphenylboronic acid (0.064 g; 0.375 mmol) in a mixture of DME-water (3:1, 1 mL) was heated at 100° C. in a sealed tube for 2.5 h. The mixture was diluted with brine and extracted with ethyl acetate. The combined organics were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of methanol (1-10%) in dichloromethane furnished 0.069 g (64%) of the title compound as a colorless oil.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined organics were dried over magnesium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash-chromatography on silica gel using a gradient of methanol (1-10%) in dichloromethane

Sources & evidence

ORD record
ord-fa957e958c4642bfab27a383f3dfa4f7
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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