Acetic Acid → 2(1H)-Quinolinone, 5-[(1R)-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-, (2Z)-2-butenedioate (1:1)

HRID 1821113Notes

Reaction equation

HRID 1821113 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1C=CC=CC=1.C1(C[O:17][C:18]2[CH:19]=[CH:20][C:21]([C@@H:29]([OH:45])[CH2:30][NH:31][CH:32]3[CH2:40][C:39]4[C:34](=[CH:35][C:36]([CH2:43][CH3:44])=[C:37]([CH2:41][CH3:42])[CH:38]=4)[CH2:33]3)=[C:22]3[C:27]=2[NH:26][C:25](=[O:28])[CH:24]=[CH:23]3)C=CC=CC=1.C(C1C=C2C(=CC=1CC)CC(NC[C@@H](C1C=CC(O)=C3C=1C=CC(=O)N3)O)C2)C.[C:75]([OH:78])(=[O:77])[CH3:76]>[Pd]>[C:1]([OH:9])(=[O:8])/[CH:2]=[CH:76]\[C:75]([OH:78])=[O:77].[CH2:41]([C:37]1[CH:38]=[C:39]2[C:34](=[CH:35][C:36]=1[CH2:43][CH3:44])[CH2:33][CH:32]([NH:31][CH2:30][C@@H:29]([C:21]1[CH:20]=[CH:19][C:18]([OH:17])=[C:27]3[C:22]=1[CH:23]=[CH:24][C:25](=[O:28])[NH:26]3)[OH:45])[CH2:40]2)[CH3:42]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6918554IndacaterolHCID 68621559HCID 68621559, compound

Product 1

HCID 98275992(1H)-Quinolinone, 5-[(1R)-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-, (2Z)-2-butenedioate (1:1)

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
55 °C

Procedure

A 1 L hydrogenation vessel is charged with 40 grams of 8-phenylmethloxy-5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-1H-quinolin-2-one benzoate and 400 mL of acetic acid. Palladium on charcoal 5% (5.44 g) is added and the reaction mass is hydrogenated for 2-8 hours until complete conversion to 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one. The mixture is filtered over a pad of filter-aid. The filtrate is concentrated at 50-60° C. under vacuum (100 mbar) to a volume of 70-90 mL. This residue is dissolved in 400 mL of ethanol and heated to 50-60° C. A solution of 11.6 g maleic acid in 24 mL ethanol is added and the resulting clear solution is seeded at an internal temperature of 50° C. with a suspension of 350 mg micronised 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one in 20 mL isopropanol. The product is crystallized by slow cooling to 0-5° C. Filtration and washing with 50 mL of ethanol followed by 25 mL of isopropanol provides 65 g crude 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one maleate which is further purified by crystallization from 1.36 L of ethanol. This gives 24.3 g pure 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one maleate as a white crystalline powder.

Workup

  1. filtrationThe mixture is filtered over a pad
  2. filtrationof filter-aid
  3. concentrationThe filtrate is concentrated at 50-60° C. under vacuum (100 mbar) to a volume of 70-90 mL
  4. dissolutionThis residue is dissolved in 400 mL of ethanol
  5. additionA solution of 11.6 g maleic acid in 24 mL ethanol is added
  6. additionthe resulting clear solution is seeded at an internal temperature of 50° C. with a suspension of 350 mg micronised 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one in 20 mL isopropanol
  7. customThe product is crystallized
  8. temperatureby slow cooling to 0-5° C
  9. filtrationFiltration
  10. washwashing with 50 mL of ethanol

Sources & evidence

ORD record
ord-a712a1bcfc254e6eb83e2479809d5c23
Source dataset
uspto-grants-2009_10
Patent number
US07605267B2

Reaction notes

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