Sodium Carbonate → 4-[4-(1-Methoxycarbonyl-ethyl)-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 409723Notes

Reaction equation

HRID 409723 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH:4]([C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1)[CH3:5].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]([O:18][C:19]([N:21]1[CH2:22][CH:23]=[C:24]([C:9]2[CH:10]=[CH:11][C:6]([CH:4]([C:3]([O:2][CH3:1])=[O:13])[CH3:5])=[CH:7][CH:8]=2)[CH2:25][CH2:26]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 10589545Methyl 2-(4-iodophenyl)propanoate

Product 1

HCID 866861114-[4-(1-Methoxycarbonyl-ethyl)-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Under inert gas atmosphere 3.43 g (2.97 mmol) Pd(PPh3)4 are added to 17.2 g (59.4 mmol) 2-(4-iodo-phenyl)-propionic acid methyl ester (Bioorg. Med. Chem. Lett. 2010, 20, 896), 20.2 g (65.3 mmol) 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester and 18.9 g (178 mmol) sodium carbonate in 200 mL 1,2-dimethoxyethane and 30 mL water. The mixture is stirred for 2 h at 100° C. and for additional 12 h at 80° C. After that time, water is added and the mixture is extracted with EtOAc (3×). The combined organic layers are washed with water (2×) and brine and dried over sodium sulphate. The solvent is evaporated and the residue is purified by column chromatography (silica gel; heptane:EtOAc gradient 100:0->60:40).

Workup

  1. extractionthe mixture is extracted with EtOAc (3×)
  2. washThe combined organic layers are washed with water (2×) and brine
  3. dry with materialdried over sodium sulphate
  4. customThe solvent is evaporated
  5. customthe residue is purified by column chromatography (silica gel; heptane:EtOAc gradient 100:0->60:40)

Sources & evidence

ORD record
ord-04dd0e2764714bccab623a2113d6eb09
Source dataset
uspto-grants-2014_06
Patent number
US08759528B2

Reaction notes

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