Diethyl Ether → Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 592342Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592342
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.CCOCC.[C:18]([N:25]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=2)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].CCN(CC)CC>[Cl-].[Cl-].[Zn+2].ClCCCl.CC(O)(C)C>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:37][C:34]2[CH:35]=[CH:36][C:31]([CH:28]3[CH2:27][CH2:26][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:30][CH2:29]3)=[CH:32][CH:33]=2)[N:7]=1

Komponenten

8

Edukt 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 21940085tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylate

Produkt 1

HCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

2,4-Dichloro-5-(trifluoromethyl)pyrimidine (4.122 g, 19.00 mmol) was stirred in a 1:1 t-BuOH:DCE mixture (400 mL) at room temperature. A 1.0 M ZnCl2 solution in Et2O (21.71 mL, 21.71 mmol) was added cautiously and the resulting mixture was stirred for 10 minutes. 1-Boc-4-(4-aminophenyl)piperidine (5.00 g, 18.1 mmol) was added followed by Et3N (6.052 mL, 43.42 mmol) and stirring continued at room temperature overnight. The volatiles were evaporated to dryness and the resulting residue was suspended in water (500 mL). After sonication for 30 minutes the suspension was filtered and the filter cake was washed with water (2×100 mL) and dried under a high vacuum to yield the title compound K3 as a tan solid (8.11 g, 98%); 1H NMR (400 MHz, d6-DMSO) δ 10.61 (s, 1H), 8.78 (s, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 4.07 (d, J=11.1 Hz, 2H), 2.80 (s, 2H), 2.65 (t, J=12.0 Hz, 1H), 1.74 (d, J=12.3 Hz, 2H), 1.42 (s, 11H). LCMS-A: rt 6.834 min; m/z 457 [M+H]+.

Aufarbeitung

  1. customat room temperature
  2. stirringstirring
  3. waitcontinued at room temperature overnight
  4. customThe volatiles were evaporated to dryness
  5. customAfter sonication for 30 minutes the suspension
  6. filtrationwas filtered
  7. washthe filter cake was washed with water (2×100 mL)
  8. customdried under a high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-a5bd20942bdc4285a46639e9bfb4d746
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238644B2

Notizen zur Reaktion

Wird geladen…