Triethylamine → 5-Methoxy-3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine

HRID 723168Notes

Reaction equation

HRID 723168 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH2:11].C(N(CC)CC)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:44][C:45]1([CH3:52])[C:49]([CH3:51])([CH3:50])[O:48][BH:47][O:46]1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:10][O:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([B:47]2[O:48][C:49]([CH3:51])([CH3:50])[C:45]([CH3:52])([CH3:44])[O:46]2)=[C:3]([NH2:11])[CH:4]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 218864892-Bromo-5-methoxy-3-methyl-phenylamine

Product 1

HCID 218865585-Methoxy-3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamineYield 99%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-bromo-5-methoxy-3-methyl-phenylamine ((Example 198: step c) 2.04 g, 6.18 mmol) in dry dioxane (100 mL) was treated with triethylamine (5.26 mL, 37.7 mmol), 2-(dicyclohexylphosphino)biphenyl (0.662 g, 1.89 mmol), and Pd(OAc)2 (0.106 g, 0.472 mmol). 4,4,5,5-Tetramethyl-1,3,2-dioxaborolane (4.09 mL, 28.3 mmol) was added slowly and the mixture heated to reflux for 1 h. The dioxane was evaporated in vacuo. The residue was taken up in EtOAc and washed with water (2×75 mL). The organic layer was filtered by gravity to remove the palladium residue, dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (10–25% EtOAc in hexanes raised in 5% increments) afforded the product 5-methoxy-3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (1.61 g, 98%) as a light brown solid. 1H NMR (CDCl3): δ 7.361 (d, 1H, J=7.6 Hz), 7.279 (d, 1H, J=8.0 Hz), 3.815 (s, 3H), 2.46 (s, 3H), 1.356 (s, 12H).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 1 h
  3. customThe dioxane was evaporated in vacuo
  4. washwashed with water (2×75 mL)
  5. filtrationThe organic layer was filtered by gravity
  6. customto remove the palladium residue
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. temperatureSilica gel chromatography (10–25% EtOAc in hexanes raised in 5% increments)

Sources & evidence

ORD record
ord-dcf049c10e2740ec97bcf5cfe442bc68
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

Loading…