Potassium Phosphate, Tribasic → tert-Butyl 4-(4-methyl-3-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

HRID 1666449ノート

反応式

HRID 1666449 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=1.Br[CH:23]=[C:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH:23]=[C:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)=[CH:4][C:3]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=1

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 45489892tert-Butyl 4-(bromomethylidene)piperidine-1-carboxylateHCID 668754484-Methyl-3-(5-(trifluoromethyl)pyridin-2-yloxy)phenylboronic acid

生成物 1

HCID 66876250tert-Butyl 4-(4-methyl-3-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate収率 29.3%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a solution of 4-methyl-3-(5-(trifluoromethyl)pyridin-2-yloxy)phenylboronic acid (1.13 g, 0.0038 mol) and tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (871 mg, 0.006 mol) in THF (10.5 mL) was added K3PO4 (2.43 g, 0.011 mol). The flask was put under vacuum and flushed with N2 three times. Water (0.19 mL) was added and the system was flushed with N2 again. PdCl2(dppf) (310 mg, 0.0004 mol) was added and the system was flushed with N2 two to three times again. The reaction mixture was refluxed at 50° C. for 1 h. The reaction mixture was concentrated, diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (2.5% EtOAc-97.5% Hexane) to give the pure title compound (0.50 g). 1H NMR (500 MHz, CDCl3): δ 8.42 (s, 1H), 7.90 (dd, J=2.25 Hz, J=8.75 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 7.03-6.98 (m, 2H), 6.89 (s, 1H), 6.31 (s, 1H), 3.49 (t, J=5.0 Hz, 2H), 3.40 (t, J=5.5 Hz, 2H), 2.47 (t, J=5 Hz, 2H), 2.30 (s, 3H), 2.13 (s, 3H), 1.46 (s, 9H).

後処理

  1. customflushed with N2 three times
  2. additionWater (0.19 mL) was added
  3. customthe system was flushed with N2 again
  4. customthe system was flushed with N2 two to three times again
  5. concentrationThe reaction mixture was concentrated
  6. additiondiluted with water
  7. extractionextracted with EtOAc
  8. extractionThe organic extract
  9. washwas washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by column chromatography (2.5% EtOAc-97.5% Hexane)

出典と根拠

ORDレコード
ord-1723cdef61ec4135ae472207751c3f93
出典データセット
uspto-grants-2011_10
特許番号
US08044052B2

反応ノート

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