Hydrochloric Acid → [6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid

HRID 1644750Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1644750
C[O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+].Cl>O1CCCC1.O>[F:24][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:25])=[O:2])[C:14]([CH3:15])=[C:13]2[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=1

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 59350825[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester

Produkt 1

HCID 46206526[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acidAusbeute 60,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester (140.8 mg, 0.419 mmol) in tetrahydrofuran (14 mL) was treated with a warm solution of lithium hydroxide monohydrate (175.8 mg, 4.19 mmol) in water (3.5 mL). The reaction mixture was stirred at room temperature for 20 hours, diluted with water, acidified with aqueous 3.0 N HCl and extracted with ethyl acetate. The ethyl acetate layers were combined, washed with brine, dried (MgSO4), filtered and concentrated. Purification by reverse phase HPLC gave 81.7 mg (60%) of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.43 (br. s, 1 H), 7.91 (dd, J=8.7, 6.3 Hz, 1 H), 7.74 (s, 1 H), 7.62 (dd, J=12.1, 1.8 Hz, 1 H), 7.33 (td, J=8.7, 1.8 Hz, 1 H), 7.03 (d, J=7.8 Hz, 2 H), 6.92 (d, J=7.8 Hz, 2 H), 4.40 (s, 2H), 3.82 (s, 2 H), 2.32 (s, 3 H), 2.21 (s, 3 H). HRMS (ES−) cald. for C21H19FO2 [(M−H)−] 321.1296, obsd. 321.1294.

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-fd8a2407489e45318b160a9c883ed7c8
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08124629B2

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