Sodium Bicarbonate → {4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

HRID 1925438Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1925438
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH3:34][O:35][CH:36]1[CH:41]([O:42][CH3:43])[CH:40]([O:44][CH3:45])[CH:39]([CH3:46])[O:38][CH:37]1[O:47][C:48](=O)[O:49]C1C=CC([N+]([O-])=O)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:34][O:35][C@@H:36]1[C@H:41]([O:42][CH3:43])[C@@H:40]([O:44][CH3:45])[C@H:39]([CH3:46])[O:38][C@H:37]1[O:47][C:48](=[O:49])[NH:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:22])[F:23])=[CH:8][CH:7]=3)[N:14]=2)=[CH:16][CH:17]=1

Komponenten

6

Edukt 4

HCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 669688834-[2-(4-Trifluoromethylphenyl)-pyrimidin-4-yl]-phenylamineHCID 67519234Carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

Produkt 1

HCID 44230217{4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl esterAusbeute 29,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel3×

Versuchsvorschrift

To a mixture cooled in an ice bath of 126 mg (0.40 mmol) of 4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenylamine in 1 mL of dry toluene was added dropwise via syringe 1.6 mL (0.80 mmol) of a 0.5 M solution of potassium hexamethyldisilazide in toluene over a 10-15 minute period. To this mixture was then added dropwise a solution of 148 mg (0.400 mmol) of carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester in 2 mL of toluene. The contents were allowed to gradually warm to room temperature and stir overnight and were added to cold saturated sodium bicarbonate. The mixture was extracted two times with chloroform and the combined extracts were dried (MgSO4). Concentration gave 130 mg which was purified by chromatography on silica gel using 9:1 DCM/EtOAc to afford 64 mg (29%) of Compound 232. 1HNMR (300 MHz, CDCl3) δ 8.87 (d, J=5.2 Hz, 1H), 8.71 (d, J=8.2 Hz, 2H), 8.26 (d, J=8.8 Hz, 2H), 7.79 (d, J=8.2 Hz, 2H), 7.65 (d, J=5.2 Hz, 1H), 7.63 (d, 2H), 6.86 (br s, 1H), 6.26 (d, J=1.9 Hz, 1H), 3.74-3.70 (m, 2H), 3.61 (s, 3H), 3.60 (s, 3H), 3.57 (s, 3H), 3.53 (m, 1H), 3.24 (t, J=9.5 Hz, 1H), 1.36 (d, J=6.0 Hz, 3H); MS (API-ES+) 549 ([M+H]+, 10), 358 (100); mp 176-179° C.

Aufarbeitung

  1. extractionThe mixture was extracted two times with chloroform
  2. dry with materialthe combined extracts were dried (MgSO4)
  3. concentrationConcentration
  4. customgave 130 mg which
  5. customwas purified by chromatography on silica gel using 9:1 DCM/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-194263db04994eec8db2305059e58d73
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178658B2

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