3-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acid → (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

HRID 20951

Reaktionsgleichung

Reaktionsgleichung von HRID 20951
[Si:1]([O:8][C@H:9]([C@H:34]1[CH2:38][C@@H:37]([O:39][CH2:40][CH2:41][CH3:42])[CH2:36][N:35]1[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[C@@H:10]([NH:20]C(=O)C1C=C(C)C=C(C(OC)=O)C=1)[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH:50][C:51]1[CH:52]=[C:53]([CH:57]=[C:58]([N:60]2[CH2:64][CH2:63][CH2:62][C:61]2=[O:65])[CH:59]=1)[C:54]([OH:56])=O.BrC1C=C(C=C(C(OC)=O)C=1)C(N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)O[Si](C(C)(C)C)(C)C)=O.N([O-])=O.[Na+]>Cl.O.CO>[Si:1]([O:8][C@H:9]([C@H:34]1[CH2:38][C@@H:37]([O:39][CH2:40][CH2:41][CH3:42])[CH2:36][N:35]1[C:43]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:44])[C@@H:10]([NH:20][C:54](=[O:56])[C:53]1[CH:57]=[C:58]([N:60]2[CH2:64][CH2:63][CH2:62][C:61]2=[O:65])[CH:59]=[C:51]([OH:50])[CH:52]=1)[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 222530273-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acidHCID 23668193Sodium NitriteHCID 67315749(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylateHCID 67316204(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-(methoxycarbonyl)-5-methylbenzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

Produkt 1

HCID 59346851(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidLösungsmittel2×HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Step I (4): 3-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acid. To a solution of 3-amino-5-(2-oxopyrrolidin-1-yl)benzoic acid (Step I (3), 140 mg, 0.63 mmol) in 2N HCl (2 mL) were added MeOH (2 mL) followed by NaNO2 (88 mg, 1.26 mmol) in portions at −10° C. After the mixture was warmed up to 0° C., H2O (3 mL) was added to the above mixture and the mixture was stirred at 95° C. for 1 h. 0.1N HCl (30 mL) was added and the mixture was extracted with ethyl acetate (50 mL) three times. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give 130 mg of the title compound: 1H NMR (CD3OD, 500 MHz) δ ppm 2.19 (2H, m), 2.62 (2H, m), 3.94 (2H, m), 7.27 (1H, m), 7.47 (1H, m), 7.66 (1H, m). MS (ESI) (M−H)− 220.12.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate (50 mL) three times
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1ace32260aad4597881a420dccd09c40
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745470B2

Verknüpfte Notizen

Wird geladen…