Water → HCID 131734732, compound

HRID 1775238Notes

Reaction equation

HRID 1775238 reaction equation
[NH2:1][C:2]1[C:3](Br)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:13]([C@@:15]1([CH3:30])[CH2:19][CH2:18][CH2:17][N:16]1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])#[CH:14].O>C1(C)C=CC=CC=1.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.[Cu]I>[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]=1[C:14]#[C:13][C@@:15]1([CH3:30])[CH2:19][CH2:18][CH2:17][N:16]1[C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21]

Participants

7

Reactant 3

HCID 962WaterHCID 13574117Methyl 3-amino-2-bromobenzoateHCID 127263151HCID 127263151, compound

Product 1

HCID 131734732HCID 131734732, compoundYield 58.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of tetrakis(triphenylphosphine)palladium(0)(1.72 g, 1.5 mmol) and CuI (0.29 g, 1.5 mmol) in 54 mL of toluene were added methyl 3-amino-2-bromobenzoate (2.3 g, 10 mmol), (R)-benzyl 2-ethynyl-2-methylpyrrolidine-1-carboxylate (3.0 g, 12 mmol), and TEA (7 mL, 50 mmol). The mixture was stirred for 18 h at 100° C. under nitrogen atmosphere. After cooling, water (20 mL) was added. The mixture was extracted with EtOAc (3×20 mL) and the combined organic layers were washed with brine (20 mL) and dried over MgSO4. The mixture was filtered, and the filtrate was evaporated to dryness. The residue was purified by column chromatography on silica gel using CH2Cl2 as eluent to provide 2.31 g of (R)-benzyl 2-((2-amino-6-(methoxycarbonyl)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate.

Workup

  1. temperatureAfter cooling
  2. extractionThe mixture was extracted with EtOAc (3×20 mL)
  3. washthe combined organic layers were washed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated to dryness
  7. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-76d0a7ab9dd04e23a294374e324b6407
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

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