Tributylphosphine → ethyl 3-(4-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl)methoxy)-3,5-difluorophenyl)propanoate

HRID 2167369Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2167369
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]2[CH2:17][OH:18])=[CH:4][CH:3]=1.[F:19][C:20]1[CH:21]=[C:22]([CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:23]=[C:24]([F:27])[C:25]=1O.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.CCCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([F:14])([F:15])[F:16])=[C:9]2[CH2:17][O:18][C:25]2[C:24]([F:27])=[CH:23][C:22]([CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:21][C:20]=2[F:19])=[CH:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 23136305Ethyl 3-(3,5-difluoro-4-hydroxyphenyl)propanoateHCID 90404801(1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl)methanol

Produkt 1

HCID 90405892ethyl 3-(4-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl)methoxy)-3,5-difluorophenyl)propanoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8900HeptaneLösungsmittel

Versuchsvorschrift

A solution of the product prepared in Step D (1.33 g, 4.84 mmol, 1 eq), ethyl 3-(3,5-difluoro-4-hydroxyphenyl)propanoate (1.78 g, 7.74 mmol, 1.6 eq), 1,1′-(azodicarbonyl)dipiperidine (2.52 g, 9.68 mmol, 2 eq) and tri-n-butylphosphine (3.08 mL, 12.1 mmol, 2.5 eq) in toluene (85 mL) was heated to 60° C. under N2. After 3 hr, heptane (170 mL) was added and the resulting suspension allowed to cool to room temperature over 30 min. The resulting white solid byproduct was filtered, washed with heptane, and the filtrate concentrated. The resulting residue was purified by flash chromatography (120 g column) eluting with 2 to 12% EtOAc/heptane to yield ethyl 3-(4-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl)methoxy)-3,5-difluorophenyl)propanoate.

Aufarbeitung

  1. filtrationThe resulting white solid byproduct was filtered
  2. washwashed with heptane
  3. concentrationthe filtrate concentrated
  4. customThe resulting residue was purified by flash chromatography (120 g column)
  5. washeluting with 2 to 12% EtOAc/heptane

Quellen und Nachweise

ORD-Eintrag
ord-b9b28305d51a48ecb1e6e2232911226e
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045454B2

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