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

HRID 1666454
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HRID 1666454 반응식
[CH3:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][N:10]=2)[CH:7]=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:3]=[C:4]([CH:5]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][N:10]=2)[CH:7]=1)[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
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참가 물질

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반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 45489892tert-Butyl 4-(bromomethylidene)piperidine-1-carboxylateHCID 668762393-Methyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)phenylboronic acid

생성물 1

HCID 66876309tert-Butyl 4-(3-methyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate수율 18.6%

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

To a solution of 3-methyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)phenylboronic acid (2.16 g, 0.007 mol) and tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (1.67 g, 0.006 mol) in THF (20 mL) was added K3PO4 (4.48 g, 0.02 mol). The flask was put under vacuum and flushed with N2 three times. Water (0.36 mL) was added and the system was flushed with N2 again. PdCl2(dppf) (571 mg, 0.0007 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 8.45 (s, 1H), 7.90 (dd, J=2.07 Hz, J=0.025 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 6.90 (s, 1H), 6.81 (d, J=18.5 Hz, 2H), 6.31 (s, 1H), 3.50 (t, J=5.25 Hz, 2H), 3.40 (t, J=5.3 Hz, 2H), 2.47 (t, J=5 Hz, 2H), 2.36 (s, 3H), 2.31 (s, 2H), 1.47 (s, 9H).

후처리

  1. customflushed with N2 three times
  2. additionWater (0.36 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)

출처 및 근거

ORD 기록
ord-600ea940bc914ffc8d62a26b36907c09
출처 데이터셋
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08044052B2

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