Triethylamine → Methyl 3-Amino-5-bromo-2-methylbenzoate

HRID 1469165Notes

Reaction equation

HRID 1469165 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:13](CC)[C@H]2CC[C@H](N(CCOC)C)CC2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(N1CCOCC1)C#C.C(N(CC)CC)C>CN(C=O)C.[Cu]I.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>[NH2:13][C:4]1[C:5]([CH3:12])=[C:6]([CH:11]=[C:2]([Br:1])[CH:3]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 4129414-(2-Propyn-1-yl)morpholineHCID 178463213HCID 178463213, compound

Product 1

HCID 24729181Methyl 3-Amino-5-bromo-2-methylbenzoateYield 126.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of methyl 5-bromo-3-(ethyl((trans)-4-((2-methoxyethyl)(methyl)amino)cyclohexyl)amino)-2-methylbenzoate (30 g, 68.02 mmol), 4-(prop-2-yn-1-yl) morpholine (25.51 g, 204 mmol) and triethylamine (20.61 g, 204 mmol) in DMF (300 mL) was bubbled Argon for 20 min. Then CuI (3.87 g, 20.36 mmol) and Pd (PPh3)4 (7.85 g, 6.79 mmol) were added and Argon was bubbled through for further 20 min. The reaction mixture was heated at 105° C. for 4 h and then cooled to room temperature. The reaction was quenched with water (100 mL) and the aqueous phase was extracted with 10% MeOH/DCM (400 mL×3). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The residue was, purified by silica gel column chromatography to afford the title compound (21 g, 63.7% yield).

Workup

  1. customArgon was bubbled through for further 20 min
  2. temperaturecooled to room temperature
  3. customThe reaction was quenched with water (100 mL)
  4. extractionthe aqueous phase was extracted with 10% MeOH/DCM (400 mL×3)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-2aa710e3f2cf4637bbeb22529c47b979
Source dataset
uspto-grants-2015_04
Patent number
US09006242B2

Reaction notes

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