O-Xylene → HCID 70654740, compound

HRID 539448Notes

Reaction equation

HRID 539448 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[CH:7]([C:10]1[CH:11]=C(C2C=CC=CC=2)[CH:13]=[C:14]([CH:27]([CH3:29])[CH3:28])[C:15]=1[NH:16][C:17](=O)[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=1)([CH3:9])[CH3:8].CO[CH:38](OC)[CH2:39][NH2:40].[C:43]1([CH3:50])[C:44](C)=[CH:45][CH:46]=[CH:47][CH:48]=1>C1COCC1>[CH:27]([C:14]1[CH:13]=[C:50]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:11]=[C:10]([CH:7]([CH3:8])[CH3:9])[C:15]=1[N:16]1[CH:38]=[CH:39][N:40]=[C:17]1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=1)([CH3:28])[CH3:29]

Participants

6

Reactant 4

HCID 7237O-XyleneHCID 24819Phosphorus pentachlorideHCID 89728Aminoacetaldehyde dimethyl acetalHCID 70654337HCID 70654337, compound

Product 1

HCID 70654740HCID 70654740, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
132.5 °C

Procedure

Phosphorous (V) pentachloride (7.99 g, 38.4 mmol) was added slowly to a solution of N-(3,5-diisopropyl-[1,1′-biphenyl]-4-yl)-3-methoxybenzamide (9.92 g, 25.6 mmol) in xylene (260 mL) with stirrer at rt under a nitrogen atmosphere. The reaction mixture was heated to 130-135° C. (oil both temp) for 1.5 h. Xylene (approximately 200 mL) was remove at 140° C. to yield a crude oil, which was cooled down to 0° C. with ice bath. 120 mL of THF was added. To this cold THF solution was added dropwise a solution of 2,2-dimethoxyethanamine (55.8 ml, 512 mmol) in THF (140 mL) over a period of 50 min. The reaction mixture was warmed up and stirred at rt overnight. The reaction mixture was concentrated in vacuum and THF (260 mL) was added. The undissolved solid (2,2-dimethoxyethanamine HCl salt) was removed by filtration. 32 mL of 6.0 N HCl was added to the filtrate and the mixture was heated at 90° C. for 3 h. The reaction mixture was cooled down and neutralized with aq. Na2CO3 to pH 11. THF was removed in vacuum and the remaining aqueous mixture was extracted with AcOEt (3×350 mL). The combined AcOEt extracts were washed with water and brine, and then purified by silica gel column chromatography using hexane/AcOEt: 7/3 as eluant. Pure fractions were combined and concentrated to afford an off-white solid (5.6 g, 53%).

Workup

  1. customXylene (approximately 200 mL) was remove at 140° C.
  2. customto yield a crude oil, which
  3. temperaturewas cooled down to 0° C. with ice bath
  4. temperatureThe reaction mixture was warmed up
  5. concentrationThe reaction mixture was concentrated in vacuum and THF (260 mL)
  6. additionwas added
  7. customThe undissolved solid (2,2-dimethoxyethanamine HCl salt) was removed by filtration
  8. addition32 mL of 6.0 N HCl was added to the filtrate
  9. temperaturethe mixture was heated at 90° C. for 3 h
  10. temperatureThe reaction mixture was cooled down
  11. customTHF was removed in vacuum
  12. extractionthe remaining aqueous mixture was extracted with AcOEt (3×350 mL)
  13. washThe combined AcOEt extracts were washed with water and brine
  14. custompurified by silica gel column chromatography
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-7941dc09267e43f6b484eb01ea7c7996
Source dataset
uspto-grants-2014_10
Patent number
US08871361B2

Reaction notes

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