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

HRID 718450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 718450
[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[S:37][C:38]([CH2:42]O)=[C:39]([CH3:41])[N:40]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.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][CH2:42][C:38]3[S:37][C:36]([CH3:35])=[N:40][C:39]=3[CH3:41])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:24])([CH3:25])[CH2:20][CH2:19]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 2776250(Dimethyl-1,3-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 118307792(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-5-[4-[(2,4-dimethylthiazol-5-yl)methoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidAusbeute 58,6 %

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), (2,4-dimethylthiazol-5-yl)methanol (22.92 mg, 0.160 mmol) and Ph3P-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)-5-(4-((2,4-dimethylthiazol-5-yl)methoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (17.7 mg, 0.031 mmol, 58.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.29-7.21 (m, 1H), 7.14-7.01 (m, 3H), 5.84 (s, 1H), 5.36-5.15 (m, 2H), 3.27 (d, J=7.7 Hz, 1H), 2.79 (t, J=11.9 Hz, 1H), 2.58 (s, 3H), 2.44 (s, 3H), 2.34 (s, 3H), 2.18 (d, J=12.5 Hz, 1H), 2.06 (s, 3H), 1.96-1.87 (m, 1H), 1.49 (br. s., 1H), 1.36-1.25 (m, 1H), 1.18 (d, J=12.8 Hz, 1H), 1.13 (s, 9H), 1.01 (d, J=11.7 Hz, 1H), 0.85 (br. s., 3H), 0.59 (br. s., 3H). LCMS (M+H)=566.6.

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-bcee8cdbabc948eb9dc2d6b6f1313cfa
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193720B2

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