Sodium Hydroxide → (2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-5-[4-[(4-methyl-2-phenyl-thiazol-5-yl)methoxy]phenyl]-3-pyridyl]acetic acid

HRID 718451

Reaktionsgleichung

Reaktionsgleichung von HRID 718451
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:35][C:36]1[N:37]=[C:38]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[S:39][C:40]=1[CH2:41]O.CCOC(/N=N/C(OCC)=O)=O.[OH-].[Na+]>C1COCC1.CO>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:41][C:40]3[S:39][C:38]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)=[N:37][C:36]=3[CH3:35])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:24])([CH3:25])[CH2:22][CH2:23]1)[C:7]([OH:9])=[O:8])([CH3:3])([CH3:2])[CH3:4]

Komponenten

7

Edukt 4

HCID 14798Sodium HydroxideHCID 736541(4-Methyl-2-phenyl-thiazol-5-yl)-methanolHCID 5462977Diethyl azodicarboxylateHCID 118314205(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate

Produkt 1

HCID 118307815(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-5-[4-[(4-methyl-2-phenyl-thiazol-5-yl)methoxy]phenyl]-3-pyridyl]acetic acidAusbeute 34,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (25 mg, 0.053 mmol), (4-methyl-2-phenylthiazol-5-yl)methanol (32.9 mg, 0.160 mmol) and Ph3-resin (69.7 mg, 0.267 mmol) in THF (2 mL) was added DEAD (0.025 mL, 0.160 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (1.067 mL, 1.067 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-((4-methyl-2-phenylthiazol-5-yl)methoxy)phenyl)pyridin-3-yl)acetic acid (11.6 mg, 0.018 mmol, 34.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.89 (d, J=7.3 Hz, 2H), 7.52-7.41 (m, 4H), 7.25 (d, J=8.1 Hz, 1H), 7.14 (t, J=7.9 Hz, 2H), 7.10-7.04 (m, 1H), 5.82 (br. s., 1H), 5.41 (q, J=12.8 Hz, 2H), 3.26 (d, J=11.7 Hz, 1H), 2.77 (br. s., 1H), 2.47 (s, 3H), 2.43 (s, 3H), 2.15 (d, J=10.3 Hz, 1H), 2.07 (s, 3H), 1.88 (br. s., 1H), 1.46 (br. s., 1H), 1.24 (br. s., 1H), 1.15 (br. s., 1H), 1.12 (s, 9H), 0.92 (d, J=10.3 Hz, 1H), 0.77 (br. s., 3H), 0.51 (br. s., 3H). LCMS (M+H)=628.6.

Aufarbeitung

  1. filtrationmixture was filtered
  2. customto remove polymer
  3. concentrationconcentrated
  4. temperatureMixture was then cooled
  5. custompurified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-2245934141eb47fe8e24213d3e3d7674
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193720B2

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