Tributylamine → tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 1394924

Reaktionsgleichung

Reaktionsgleichung von HRID 1394924
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([CH:8]2[CH:12]=[CH:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)[CH:7]=1.[C:21]([Si:25]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31](I)[CH:30]=1)([CH3:27])[CH3:26])([CH3:24])([CH3:23])[CH3:22].C(N(CCCC)CCCC)CCC.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:25]([O:28][C:29]1[CH:34]=[C:33]([CH:11]2[CH:12]=[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[F:20])[CH2:9][N:10]2[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH:32]=[CH:31][CH:30]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:27])[CH3:26]

Komponenten

7

Edukt 4

HCID 7622TributylamineHCID 11773TriphenylarsineHCID 27572803-(t-Butyldimethylsiloxy)iodobenzeneHCID 59656601tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate

Produkt 1

HCID 59682334tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A deoxygenated mixture of tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate (17-1, 1.100 g, 3.69 mmol, 1 equiv), tert-butyl(3-iodophenoxy)dimethylsilane (1.85 g, 5.54 mmol, 1.50 equiv), tributylamine (1.76 mL, 7.39 mmol, 2.00 equiv), triphenylarsine (0.453 g, 1.48 mmol, 0.400 equiv), and palladium acetate (0.166 g, 0.739 mmol, 0.200 equiv) in DMF (10 mL) was heated at 65° C. for 20 hours. The reaction mixture was partitioned between water (100 mL) and ethyl acetate (2×85 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexanes initially, grading to 50% ethyl acetate in hexanes) to provide tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (17-2) as an orange oil. 1H NMR (300 MHz, CDCl3) major rotamer: δ 7.11-6.53 (m, 7H), 6.11 (s, 1M), 5.32 (m, 1H), 4.53 (m, 2H), 1.09 (s, 9H), 0.79 (s, 9H), 0.00 (s, 6H). LRMS m/z (M+H) 504.1 found, 504.2 required.

Aufarbeitung

  1. customThe reaction mixture was partitioned between water (100 mL) and ethyl acetate (2×85 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (100% hexanes initially

Quellen und Nachweise

ORD-Eintrag
ord-fae7ad455d0b4a529d35de8eb29c400e
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07348440B2

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