1,2-Dimethoxyethane → (R)-2-[3-(6-Chloro-pyridin-3-yl)-benzyl]-morpholine-4-carboxylic Acid Tert-butyl Ester

HRID 2252998Notes

Reaction equation

HRID 2252998 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].COCCOC.[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=1.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:32]3[CH:31]=[N:30][C:29]([Cl:28])=[CH:34][CH:33]=3)[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 38450342-Chloropyridine-5-boronic acidHCID 67073309N-Boc-(R)-2-(3-bromobenzyl)morpholine2×

Product 1

HCID 86607060(R)-2-[3-(6-Chloro-pyridin-3-yl)-benzyl]-morpholine-4-carboxylic Acid Tert-butyl EsterYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To the solution of 0.30 g (0.84 mmol) (R)-2-(3-bromo-benzyl)-morpholine-4-carboxylic acid tert-butyl ester (example 97, intermediate (d)) in 12 mL 1,2-dimethoxyethane 97 mg (84 μmol) tetrakis(triphenylphosphine)palladium(0) were added. After 30 min. 0.48 g (3.0 mmol) 2-chloropyridine-5-boronic acid and 0.22 g (2.1 mmol) sodium bicarbonate dissolved in 6 mL water were added successively and the reaction stirred for 2.5 h under reflux. After cooling down to room temperature the reaction mixture was poured on saturated aqueous potassium carbonate solution and extracted three times with ethyl acetate. The organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography using MPLC on silica gel with ethyl acetate: n-heptane (1:1) as eluant to give the compound as colorless oil (35%).

Workup

  1. additionwere added successively
  2. temperatureunder reflux
  3. extractionextracted three times with ethyl acetate
  4. washThe organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a60f4f835c624abc96a6b0247372d6d2
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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