Trifluoroacetic acid → 2-Pyrimidinecarboxylic acid, 5-[[3-methyl-1-[4′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]butyl]amino]-, methyl ester

HRID 2173851Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2173851
[CH3:1][O:2][C:3]([C:5]1[N:10]=[CH:9][C:8]([N:11](C(OC(C)(C)C)=O)[CH:12]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:19][CH:18]=2)[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:7][N:6]=1)=[O:4].FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]([NH:11][CH:12]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=3)=[CH:19][CH:18]=2)[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:9][N:10]=1)=[O:4]

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acid2×HCID 68062019(+/-)-5-{Tert-butoxycarbonyl-[3-methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butyl]-amino}-pyrimidine-2-carboxylic acid methyl ester

Produkt 1

HCID 679837782-Pyrimidinecarboxylic acid, 5-[[3-methyl-1-[4′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]butyl]amino]-, methyl esterAusbeute 50,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(+/−)-5-{tert-Butoxycarbonyl-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butyl]-amino}-pyrimidine-2-carboxylic acid methyl ester (1.498 g impure) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (3 mL) was added. This was stirred at room temperature. At 70 min, another 3 mL of trifluoroacetic acid was added. At 90 min, the reaction was concentrated and the material was partitioned between ethyl acetate and sat. NaHCO3. The aqueous layer was extracted with ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave (+/−)-5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carboxylic acid methyl ester (0.620 g) as a white foam. 1H NMR (400 MHz, CDCl3, δ): 8.16 (s, 2H) 7.67-7.73 (m, 2H) 7.61-7.66 (m, 2H) 7.56 (d, J=8.2 Hz, 2H) 7.39 (d, J=8.2 Hz, 2H) 4.68 (d, J=5.7 Hz, 1H) 4.46-4.57 (m, 1H) 3.98 (s, 3H) 1.79-1.92 (m, 1H) 1.64-1.79 (m, 2H) 1.05 (d, J=6.2 Hz, 3H) 0.99 (d, J=6.2 Hz, 3H); MS (M+1): 444.3.

Aufarbeitung

  1. waitAt 90 min
  2. concentrationthe reaction was concentrated
  3. customthe material was partitioned between ethyl acetate and sat. NaHCO3
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organics dried over MgSO4
  6. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-0570daac0bfe4877a2a4eda8681be87c
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09056834B2

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