Lithium hydroxide, monohydrate → Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

HRID 1485155Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1485155
O[Li:2].O.C[O:5][C:6](=[O:46])[CH2:7][C:8]1[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[CH2:34][CH2:33][CH2:32][N:31]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1>C1COCC1.O.CO>[C:38]([O:37][C:35]([N:31]1[CH2:32][CH2:33][CH2:34][CH:29]([C:26]2[CH:25]=[CH:24][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:42]=[CH:43][CH:44]=[CH:45][C:8]=4[CH2:7][C:6]([O-:46])=[O:5])[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][N:15]=3)=[CH:28][CH:27]=2)[CH2:30]1)=[O:36])([CH3:41])([CH3:39])[CH3:40].[Li+:2]

Komponenten

6

Edukt 2

HCID 168937Lithium hydroxide, monohydrateHCID 71209222tert-Butyl 3-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Produkt 1

HCID 68282896Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetateAusbeute 101,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

LiOH.H2O (0.052 g, 1.25 mmol) was added to tert-butyl 3-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I26) (0.249 g, 0.416 mmol) in THF (10 mL), water (2.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir for 2 hours at 40° C. and then 20 hours at room temperature. The volatiles were removed in vacuo and the residue was diluted with EtOAc (70 mL) and 2 M aq. NaOH (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (70 mL), the organic layers were combined, washed with brine (70 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I27) (0.250 g, 100% yield) as an off-white oily solid; 1H NMR (400 MHz, d6-DMSO) δ 10.23 (s, 1H), 8.64 (s, 1H), 7.72-7.60 (m, 2H), 7.25-7.00 (m, 6H), 4.01-3.88 (m, 2H), 3.48 (s, 2H), 3.13-2.92 (m, 4H), 2.86-2.63 (m, 2H), 1.91-1.81 (m, 1H), 1.72-1.54 (m, 2H), 1.48-1.34 (m, 10H). LCMS Method C: rt 6.71 min; m/z 585.3 [M+H]+.

Aufarbeitung

  1. custom20 hours
  2. customat room temperature
  3. customThe volatiles were removed in vacuo
  4. additionthe residue was diluted with EtOAc (70 mL) and 2 M aq. NaOH (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (70 mL)
  7. washwashed with brine (70 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-3106af84d1b24e498d58c72fdc749d20
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09421205B2

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