Hydrochloric Acid → (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acid

HRID 718468Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 718468
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:45])=[N:17][C:18]([CH3:44])=[C:19]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:30][CH:29]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)[C:9]([O:11]C(C)C)=[O:10])([CH3:6])([CH3:5])[CH3:4].Cl>C(O)C>[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:45])=[N:17][C:18]([CH3:44])=[C:19]([C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:32][CH:33]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 118307686(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate

Produkt 1

HCID 118307846(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acidAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

The 1.32 mL of 1M sodium hydroxide (52.8 mg, 1.32 mmol) was added to a (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate (130 mg, 0.22 mmol) in ethanol (1 mL) and stirred for 24 h at 85° C. An additional 0.31 mL sodium hydroxide was added and the reaction was continued for 24 h. The reaction mixture was neutralized with 1N HCl solution, extracted with EtOAc, and the organic layer was washed with brine, and dried (MgSO4). The crude material was purified by prep HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acid 58 mg (48%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.19 (d, J=9.2 Hz, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.00-6.95 (m, 3H), 5.84 (s, 1H), 4.22 (t, J=6.6 Hz, 2H), 3.44-3.39 (m, 4H), 3.06 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.03 (s, 3H), 1.72-1.68 (m, 1H), 1.49 (d, J=12.1 Hz, 1H), 1.34 (d, J=7.0 Hz, 1H), 1.24-1.20 (m, 1H), 1.12 (s, 9H), 1.06-1.01 (m, 1H), 0.83 (d, J=3.7 Hz, 3H). UPLC (M+H)=549.6.

Aufarbeitung

  1. waitthe reaction was continued for 24 h
  2. extractionextracted with EtOAc
  3. washthe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customThe crude material was purified by prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-4a7fde5b43124059bc4b700d7353924f
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193720B2

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