Tributylphosphine → 6-[Cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-7-{2-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

HRID 1096871

Reaktionsgleichung

Reaktionsgleichung von HRID 1096871
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([Cl:9])[CH:5]=[C:4]([CH3:10])[CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:25][CH:24]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:20]([CH2:21][C:22]([C:50]3[S:54][C:53]([O:55][CH2:56][CH2:57]O)=[N:52][CH:51]=3)=[C:23]2[C:34](=[O:49])[N:35]([CH:46]2[CH2:48][CH2:47]2)[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[C:38]=2[CH3:45])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].P(CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1.CCOCC>[C:11]([O:15][C:16]([N:18]1[CH2:25][CH:24]2[N:26]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH:20]([CH2:21][C:22]([C:50]3[S:54][C:53]([O:55][CH2:56][CH2:57][O:8][C:7]4[C:2]([Cl:1])=[CH:3][C:4]([CH3:10])=[CH:5][C:6]=4[Cl:9])=[N:52][CH:51]=3)=[C:23]2[C:34](=[O:49])[N:35]([CH:46]2[CH2:47][CH2:48]2)[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[C:38]=2[CH3:45])[CH2:19]1)=[O:17])([CH3:12])([CH3:13])[CH3:14]

Komponenten

6

Edukt 3

HCID 13831TributylphosphineHCID 170772,6-Dichloro-4-methylphenolHCID 685707976-[Cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-7-[2-(2-hydroxyethoxy)thiazol-5-yl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

Produkt 1

HCID 685710656-[Cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-7-{2-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl esterAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A sol. of 2,6-dichloro-p-cresol (0.55 mmol; 97 mg) in toluene (4.8 mL) was treated with compound E9 (0.37 mmol; 250 mg) followed by azodicarboxylic dipiperidide (0.73 mmol; 184 mg) and PBu3 (1.28 mmol; 0.27 mL). The reaction mixture was stirred at 80° C. After 1 h, the reaction mixture was allowed to cool to rt, diluted with Et2O (50 mL), filtrated, and the filtrate was washed with NaOH 1M (50 mL) and brine (50 mL). The org. extract was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 30:70) yielded the title compound (0.23 g, 76%). LC-MS: tR=1.25 min; ES+: 843.29.

Aufarbeitung

  1. temperatureto cool to rt
  2. filtrationfiltrated
  3. washthe filtrate was washed with NaOH 1M (50 mL) and brine (50 mL)
  4. extractionextract
  5. dry with materialwas dried over MgSO4
  6. filtrationfiltered
  7. customthe solvents were removed under reduced pressure
  8. customPurification of the residue by FC (EtOAc/heptane 30:70)

Quellen und Nachweise

ORD-Eintrag
ord-8113673050884606b0e167c280617300
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08138340B2

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