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Potassium Hydroxide → 4'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

HRID 538001
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 538001
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:17]C)=[O:16])=[CH:11][C:10]=2[CH3:19])=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:21]=1[CH2:30][N:31]1[CH2:36][CH2:35][C@@H:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[O:43][CH3:44])[O:33][C:32]1=[O:45].[OH-].[K+]>CO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:17])=[O:16])=[CH:11][C:10]=2[CH3:19])=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:22][C:21]=1[CH2:30][N:31]1[CH2:36][CH2:35][C@@H:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[O:43][CH3:44])[O:33][C:32]1=[O:45]
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Komponenten

4

Edukt 2

HCID 14797Potassium HydroxideHCID 24740082methyl 4'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Produkt 1

HCID 247400844'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887
Methanol
Lösungsmittel

Versuchsvorschrift

To a solution of methyl 4′-methoxy-2″-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (55.4 mg, 0.0358 mmol) in MeOH (1.5 mL) was added 4 M KOH solution (0.8 mL). The reaction was stirred at room temperature for 6 hours, and then quenched with 1 N HCl (5 mL) and diluted with EtOAc (15 mL). The aqueous layer was extracted with EtOAc (10 mL), and the combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) to afford 4′-methoxy-2″-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS=606.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.84-8.01 (m, 2H), 7.60-7.67 (m, 2H), 7.26-7.42 (m, 5H), 6.79-7.16 (m, 4H), 5.58 (dd, J=9.3, 2.7 Hz), 5.27 (dd, J=9.4, 2.6 Hz), 4.84 (d, J=14.9 Hz), 4.77 (d, J=15.6 Hz), 4.48-4.54 (m, 1H), 3.87 (s), 3.85 (s), 3.81 (s), 3.64 (s), 2.86-3.20 (m, 2H), 2.38 (s), 2.33 (s), 1.80-2.24 (m, 2H).

Aufarbeitung

  1. customquenched with 1 N HCl (5 mL)
  2. additiondiluted with EtOAc (15 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (10 mL)
  4. washthe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-9691f7af5fa04117bd6d11ac0cd8a20a
Quelldatensatz
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08865707B2

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