Sodium Carbonate → Methyl 5-(ethylamino)-4-methyl-4'-(morpholinomethyl)[1,1'-biphenyl]-3-carboxylate

HRID 1616431Notes

Reaction equation

HRID 1616431 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:13][CH2:14][CH3:15])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].CC1(C)C(C)(C)OB([C:24]2[CH:36]=[CH:35][C:27]([CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:26][CH:25]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[CH2:14]([NH:13][C:4]1[C:5]([CH3:12])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=[C:2]([C:24]2[CH:25]=[CH:26][C:27]([CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:35][CH:36]=2)[CH:3]=1)[CH3:15]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27955024-((Morpholino)methyl)phenylboronic acid pinacol esterHCID 70872675Methyl 5-bromo-3-(ethylamino)-2-methylbenzoate

Product 1

HCID 70872874Methyl 5-(ethylamino)-4-methyl-4'-(morpholinomethyl)[1,1'-biphenyl]-3-carboxylateYield 98.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of methyl 5-bromo-3-(ethylamino)-2-methylbenzoate (600 mg, 2.2 mmol) and 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]morpholine (1.0 g, 3.3 mmol) in dioxane (5 mL), aqueous 2M Na2CO3 solution (3.96 mL, 7.93 mmol) was added and solution was purged with argon for 15 min. Then Pd(PPh3)4 (255 mg, 0.22 mmol) was added and argon was purged again for 15 min. Reaction mass was heated at 100° C. for 4 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by column chromatographic purification afforded the desired compound (800 mg, 98%).

Workup

  1. customsolution was purged with argon for 15 min
  2. customargon was purged again for 15 min
  3. customReaction mass
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM (3 times)
  6. dry with materialCombined organic layer was dried over sodium sulphate
  7. customRemoval of the solvent under reduced pressure
  8. customfollowed by column chromatographic purification

Sources & evidence

ORD record
ord-60377308a1744522955a1b1552113c20
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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